Cancer Biomarkers - Volume 21, issue 1

Authors: Sun, Si | Wu, Qi | Song, Junlong | Sun, Shengrong

Article Type: Research Article

Abstract: Besides the crucial role of hyperinsulinemia in the development of breast cancer with Type 2 diabetes mellitus (T2DM), it has been shown that hyperglycemia could contribute to promote cancer progression. A remarkable association within hyperglycemia, PKCδ and Ubiquitin-proteasome system (UPS) has been reported, suggesting that PKCδ may mediate high glucose-induced UPS activation in breast cancer cells. Although the independent effects of PKCδ or UPS on breast cancer and T2DM are increasingly supported by experimental evidence, the complex interactional link between PKCδ and UPS is still unclear. Hence, we …focus on the relationship between PKCδ and UPS in breast cancer with T2DM. We hypothesize that PKCδ may have the function to regulate the activity of UPS. Further, we speculate that PKCδ combine with proteasome α 2 promoter, that indicate PKCδ regulate the function of UPS by change the composition of proteasome. Therefore, we surmise that PKCδ mediated high glucose-induced UPS activation in breast cancer cells, and specific PKCδ inhibitor rottlerin significantly suppressed elevated glucose induced the activity of UPS. We hope that our paper will stimulate further studies the relationship between PKCδ and UPS, and a new targeted therapy and early medical intervention for PKCδ could be a useful option for breast cancer cases complicated with T2DM or hyperglycemia. Show more

Keywords: Protein kinase C δ, Ubiquitin-proteasome system, breast cancer

DOI: 10.3233/CBM-170451

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 1-9, 2018

Authors: Liu, Yanni | Nan, Fangfang | Lu, Kexin | Wang, Yunfang | Liu, Yu | Wei, Shuangyan | Wu, Ruixue | Wang, Ying

Article Type: Research Article

Abstract: BACKGROUND: Understanding the molecular mechanisms is important in development and therapy of endometrioid endometrial adenocarcinoma. OBJECTIVE: To identify key genes in endometrioid endometrial adenocarcinoma. METHODS: The data of mRNA, miRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) database and differential analysis was performed. Then, bioinformatic analysis was used to explore the regulatory mechanisms of miRNA and DNA methylation on gene expression. The regulatory network between differentially expressed miRNAs and target genes was established. Finally, the quantitative RT-PCR was applied to validate the bioinformatics results. RESULTS: We …obtained biological omics data of 381 patients with endometrioid endometrial adenocarcinoma from TCGA data portal. After data processing, up to 2068 DEGs and 69 differentially expressed miRNAs were identified. Prediction and correlation analysis revealed that 175 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. After the integrated analysis of differentially methylated CpG islands and DEGs, 16 related genes were obtained. The quantitative RT-PCR results were roughly consistent with the bioinformatics analysis. CONCLUSIONS: The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1, PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of endometrioid endometrial adenocarcinoma and could be used as potential therapeutic targets for the disease. Show more

Keywords: Differentially expressed genes, DNA methylation, endometrioid endometrial adenocarcinoma, miRNAs

DOI: 10.3233/CBM-170164

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 11-21, 2018

Authors: Chen, Min | Wu, Xiaoliang | Ma, Wenjuan | Zhou, Qianghua | Wang, Xing | Zhang, Rongxin | Wang, Jiahong | Yang, Xianzi

Article Type: Research Article

Abstract: BACKGROUND: A recent study has demonstrated that the long non-coding RNA VPS9D1-AS1 is highly expressed in colorectal cancer and predicts poor prognosis. However, roles of VPS9D1-AS1 in gastric cancer remained poorly understood. OBJECTIVE: The aim of this study is to decipher the expression of VPS9D1-AS1 in gastric cancer (GC) patients, so as to assess whether or not it could be used as a novel biomarker for prognosis in gastric cancer patients. METHODS: The expression of VPS9D1-AS1 was examined in cancer tissues and paired adjacent non-tumorous tissues from 126 gastric cancer patients using qRT-PCR. …Correlations between the expression of VPS9D1-AS1 and clinicopathological parameters and patients’ survival were analyzed. RESULTS: VPS9D1-AS1 expression was downregulated in gastric cancer tissues than that in adjacent non-tumorous tissues (P < 0.001). VPS9D1-AS1 expression level was markedly correlated with tumor size and TNM stage in gastric cancer. Kaplan-Meier analysis showed low expression of VPS9D1-AS1 were correlated with poor overall and disease free survival. On multivariate analysis, the hazard ratio of VPS9D1-AS expression was 0.30 (95% CI = 0.13–0.66, P = 0.003) for overall survival. CONCLUSIONS: Overall, our data suggest that downregulated VPS9D1-AS1 may be used as a novel prognosis predictor of gastric cancer. Show more

Keywords: Long non-coding RNA, VPS9D1-AS1, gastric cancer, downregulation

DOI: 10.3233/CBM-170172

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 23-28, 2018

Authors: Oakley-Girvan, Ingrid | Davis, Sharon Watkins

Article Type: Research Article

Abstract: BACKGROUND: Detecting volatile organic compounds (VOCs) could provide a rapid, noninvasive, and inexpensive screening tool for detecting cancer. OBJECTIVE: In this systematic review, we identified specific exhaled breath VOCs correlated with lung, colorectal, and breast cancer. METHODS: We identified relevant studies published in 2015 and 2016 by searching Pubmed and Web of Science. The protocol for this systematic review was registered in PROSPERO and the PRISMA guidelines were used in reporting. VOCs and performance data were extracted. RESULTS: Three hundred and thirty three records were identified and 43 papers were …included in the review, of which 20 were review articles themselves. We identified 17 studies that listed the VOCs with at least a subset of statistics on detection cutoff levels, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and gradient. CONCLUSIONS: Breath analysis for cancer screening and early detection shows promise, because samples can be collected easily, safely, and frequently. While gas chromatography-mass spectrometry is considered the gold standard for identifying specific VOCs, breath analysis has moved into analyzing patterns of VOCs using a variety of different multiple sensor techniques, such as eNoses and nanomaterials. Further development of VOCs for early cancer detection requires clinical trials with standardized breath sampling methods. Show more

Keywords: Exhaled breath, volatile organic compounds (VOCs), biomarkers, lung cancer, colorectal cancer, breast cancer

DOI: 10.3233/CBM-170177

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 29-39, 2018

Authors: Trojani, Alessandra | Pungolino, Ester | Rossi, Giuseppe | D’Adda, Mariella | Lodola, Milena | Camillo, Barbara Di | Perego, Alessandra | Turrini, Mauro | Orlandi, Ester | Borin, Lorenza | Iurlo, Alessandra | Malato, Simona | Spina, Francesco | Latargia, Maria Luisa | Lanza, Francesco | Artale, Salvatore | Anghilieri, Michela | Carraro, Maria Cristina | Canal, Gabriella De | Morra, Enrica | Cairoli, Roberto

Article Type: Research Article

Abstract: BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions.

DOI: 10.3233/CBM-170209

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 41-53, 2018

Authors: Bao, Xu | Duan, Junyao | Yan, Yongji | Ma, Xin | Zhang, Yu | Wang, Hanfeng | Ni, Dong | Wu, Shengpan | Peng, Cheng | Fan, Yang | Gao, Yu | Li, Xintao | Chen, Jianwen | Du, Qingshan | Zhang, Fan | Zhang, Xu

Article Type: Research Article

Abstract: BACKGROUND: Renal cell carcinoma (RCC) is one of the most malignant genitourinary diseases worldwide. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs in the human genome that are involved in RCC initiation and progression. OBJECTIVE: To investigate the expression of PVT1 in ccRCC and evaluate its correlation with clinicopathologic characteristics and patients’ survival. METHODS: Quantitative real-time PCR was performed to examine PVT1 expression in 129 ccRCC tissue samples and matched adjacent normal tissue samples. The relationship of PVT1 expression with clinicopathologic characteristics and clinical outcome was evaluated. RESULTS: …We identified the lncRNA PVT1, which was upregulated in clear cell renal cell carcinoma (ccRCC) tissues when compared with corresponding controls. Furthermore, PVT1 expression was positively associated with gender, tumor size, pT stage, TNM stage, and Fuhrman grade. Kaplan-Meier survival analysis showed that patients with high PVT1 expression had shorter disease-free survival (DFS) and overall-survival (OS) than those with low PVT1 expression, and multivariate analysis identified PVT1 as an independent prognostic factor in ccRCC. CONCLUSIONS: PVT1 may be an oncogene as well as may promote metastasis in ccRCC and could serve as a potential biomarker to predict the prognosis of ccRCC patients. Show more

Keywords: Long noncoding RNA, PVT1, clear cell renal cell carcinoma, prognosis

DOI: 10.3233/CBM-170251

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 55-63, 2018

Authors: Zhou, Rong-Miao | Li, Yan | Liu, Jiang-Hui | Wang, Na | Huang, Xi | Cao, Shi-Ru | Shan, Bao-En

Article Type: Research Article

Abstract: BACKGROUND: The most important anti-tumor immune response is mediated by T lymphocytes. The interaction of programmed death-1 ligand-1 (PD-L1) with its receptor provides an inhibitory signal in T lymphocytes activation and proliferation. OBJECTIVE: This study aimed to investigate whether polymorphisms of PD-L1 were associated with the risk and prognosis of esophageal squamous cell carcinoma (ESCC) in a high-incidence population from Northern China. METHODS: PD-L1 rs2890658 A/C and rs4143815 C/G single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method in 575 ESCC patients and 577 healthy controls. …RESULTS: There was no significant difference in the genotype frequencies of these two SNPs between the ESCC patients and the healthy controls. However, for rs2890658 A/C SNP, compared with the C/C genotype, the A/C genotype increased the risk of ESCC for the smokers (OR = 1.513, 95% CI = 1.006–2.287). Among the 575 ESCC patients, the survival information of 202 ESCC patients was collected. Neither the rs2890658 A/C SNP nor the rs4143815 C/G SNP was associated with the survival of ESCC patients. CONCLUSIONS: PD-L1 rs2890658 A/C SNP might be used as risk marker of the susceptibility to ESCC for the Han nationality in a high-incidence population from Northern China. Show more

Keywords: Esophageal squamous cell carcinoma, programmed death-1 ligand-1, polymorphism, prognosis, risk

DOI: 10.3233/CBM-170269

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 65-71, 2018

Authors: Zhu, Xiaoqin | Chen, Fang | Shao, Yongfu | Xu, Dingli | Guo, Junming

Article Type: Research Article

Abstract: BACKGROUND: Accumulating evidences have shown that long non-coding RNAs (lncRNAs), longer than 200 nucleotides in length, play a crucial role in cancer occurrence and development. However, the relationships between most lncRNAs and gastric carcinogenesis remain poorly understood. OBJECTIVE: To explore the diagnostic value of one typical lncRNA, long intergenic non-protein coding RNA 1006 (LINC01006), in gastric cancer. METHODS: First, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression levels of LINC01006 in various gastric tissues from gastric cancer patients, healthy controls, and gastric dysplasia. Next, the correlation between LINC01006 …expression levels and clinicopathological features of patients with gastric cancer was assessed. Finally, the relative levels of LINC01006 in gastric cancer cell lines comparing to normal gastric epithelial cell line were analyzed. RESULTS: LINC01006 levels in cancer tissues were significantly lower than those in adjacent normal tissues (P < 0.001) and healthy control tissues (P < 0.001). Its expression was associated with age (P = 0.013), tumor location (P = 0.022), tumor size (P = 0.030), and venous invasion (P = 0.018). Moreover, expression of LINC01006 was downregulated in two gastric cancer cell lines, MGC-803 (P < 0.05) and AGS (P < 0.001) compared to normal gastric epithelial cell line GES-1. CONCLUSIONS: All the data implied that LINC01006 may be a novel biomarker for gastric cancer. Show more

Keywords: Cancer diagnosis, gastric cancer, long non-coding RNA, LINC01006, tumor biomarker

DOI: 10.3233/CBM-170273

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 73-80, 2018

Authors: Guo, Xiaojing | Liu, Yujie | Huang, Xia | Wang, Yun | Qu, Jin | Lv, Yingpin

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Relaxin is a short circulating peptide hormone. The aim of this study was to understand the role of relaxin in progression of epithelial ovarian cancer (EOC) and to assess its diagnostic and prognostic significance. METHODS: A total of 124 patients with EOC, 46 patients with benign ovarian diseases, and 50 healthy controls were recruited. Serum levels of relaxin were determined by ELISA method. The relationship between serum relaxin level and each of the clinicopathological parameters was analyzed using the χ 2 test. Survival curves were plotted using the Kaplan-Meier …method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: The results showed that serum relaxin level was significantly higher in patients with EOC than those with benign ovarian diseases and healthy controls (p < 0.01). Serum relaxin level was associated with FIGO stage, lymph node metastasis, tumor resectability, survival of the patients, chemotherapy and tumor recurrence (p < 0.05). Analysis using the Kaplan-meier method indicated that patients with high serum relaxin had significantly shorter overall survival time than those with low relaxin (p < 0.01). In a multivariate analysis along with clinical prognostic parameters, serum relaxin was identified as an independent adverse prognostic variable for survival. CONCLUSIONS: These results indicated that serum relaxin may be a clinically useful indicator for diagnostic and prognostic evaluation in EOC patients. Show more

Keywords: Epithelial ovarian cancer, metastasis, prognosis, marker, relaxin

DOI: 10.3233/CBM-170278

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 81-87, 2018

Authors: Zhang, Yijun | Jin, Xintian | Wang, Zhe | Zhang, Xiaokai | Liu, Shen | Liu, Gang

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) exert important functions involved in tumorigenesis and cancer progression including esophageal squamous cell cancer (ESCC), however, the clinical role and underlying biological function of Small Nucleolar RNA Host Gene 1 (SNHG1) in ESCC is not well known. METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) was used to detect the SNHG1 expression levels in ESCC tissues and adjacent non-cancerous tissues. Chi-square test was used to evaluate the association between clinicopathological features and SNHG1 expression in ESCC patients, Kaplan-Meier curve and log rank test was performed to analyze the association between overall survival …and SNHG1 expression. Cell proliferation and invasion was assessed by MTT assay, colony formation, and transwell cell invasion assays. Western blot were also performed to examine protein expression levels of E-cadherin, Vimentin and N-cadherin, Notch 1 and Hes-1. RESULTS: We demonstrated that lncRNA SNHG1 was significantly up-regulated in ESCC tissues compared with adjacent non-cancerous tissues in ESCC patients. Meanwhile, increased lncRNA SNHG1 expression levels markedly correlated with lymph node metastasis, depth of invasion, TNM stage and reduced over survival time in ESCC patients. Furthermore, MTT assay, colony formation, transwell cell invasion, qRT-PCR and Western-blot assays demonstrated that knockdown of lncRNA SNHG1 could inhibit cell proliferation and cell invasion capacity and cell Epithelial-Mesenchymal Transition (EMT) phenomenon by up-regulation E-cadherin and down-regulating Vimentin and N-cadherin in ESCC cells. Besides, we demonstrated that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 and Hes-1 expression levels in ESCC cells. CONCLUSIONS: These results indicated that lncRNA SNHG1 may be a potential predictor of prognosis in ESCC patients and a novel target for ESCC treatment. Show more

Keywords: Long non-coding RNA, esophageal squamous cell cancer, SNHG1, cell invasion, cell proliferation

DOI: 10.3233/CBM-170286

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 89-96, 2018

Authors: Yuan, Linjing | Wan, Jianxin | Huang, Chumei | Liang, Jingjing | Liu, Min | Yue, Caifeng | Li, Laisheng

Article Type: Research Article

Abstract: BACKGROUND: Early detection and differentiation diagnosis of a pelvic mass (PM) is crucial in improving the prognosis of patients with epithelial ovarian cancer (EOC). C-C motif chemokine ligand 18 (CCL18) was reported as a chemokine-mediated tumor-related inflammation that can be detected in serum and may correlate with cancer patients’ prognosis. OBJECTIVE: We performed this study to investigate the relationship between CCL18 levels and clinical characteristics of EOC patients, and to explore their diagnostic and prognostic values. METHODS: CCL18 serum concentrations were detected by ELISA in 187 patients with EOC, 126 patients with benign …PMs, and 118 healthy controls. CCL18 serum levels were analyzed in the context of patients’ clinicopathological information, and ROC analyses were performed to determine the effect of CCL18 on distinguishing benign and malignant PMs. The ability of CCL18 to serve as an EOC biomarker was compared with CA125. Further survival analyses were carried out to assess the prognostic value of CCL18 in EOC patients. RESULTS: Mean serum CCL18 levels were elevated in benign PM patients and were even higher in EOC patients than in healthy controls; furthermore, high CCL18 expression was associated with worse International Federation of Gynecology and Obstetrics (FIGO) staging and predicted a poorer survival of the patient. When compared with CA125, although the sensitivity and negative predictive values (NPV) of serum CCL18 were lower, its specificity and positive predictive values (PPV) were higher. CONCLUSIONS: Serum CCL18 was elevated in patients with EOC and could serve as a new tumor biomarker, which also predicted a poor survival of the patient. Show more

Keywords: CCL18, ovarian cancer, prognosis, biomarker, CA125

DOI: 10.3233/CBM-170305

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 97-104, 2018

Authors: Yu, Liang | Chen, Jun | Liu, Yu | Zhang, Zengfeng | Duan, Shaobin

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

Keywords: miR-937, FOXL2, gastric cancer, proliferation, invasion

DOI: 10.3233/CBM-170310

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 105-116, 2018

Authors: Liu, Suoning | Suo, Jian | Wang, Chunxi | Sun, Xuan | Wang, Daguang | He, Liang | Zhang, Yang | Li, Wei

Article Type: Research Article

Abstract: Numerous studies have proved that microRNAs (miRNAs) play crucial roles in the tumorigenesis and progression of gastric cancer (GC). Our study was to investigate the correlation between miR-338-3p expression and clinical features as well as prognosis of GC. A total of 138 GC tissue specimens and adjacent non-cancerous tissues were collected for further analysis, then quantitative PCR method was used to detect the relative miR-338-3p expression. Our study showed that tissue miR-338-3p level was greatly decreased in cancer tissues compared with paired normal tissues. Furthermore, loss of tissue miR-338-3p was positively associated with aggressive clinical characteristics (advanced clinical stage, poorer …differentiation and lymph node invasion), shorter overall survival and recurrence free survival. Finally, tissue miR-338-3p expression was confirmed to be an independent prognostic factor for GC. Overall, our findings indicate that miR-338-3p acts as a tumor suppressor in GC and tissue miR-338-3p might serve as a novel prognostic biomarker of GC. Show more

Keywords: Gastric cancer, miR-338-3p, prognosis, biomarker

DOI: 10.3233/CBM-170339

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 117-122, 2018

Authors: Xie, Pengmu | Cao, Hongying | Li, Ying | Wang, Jianhua | Cui, Zhumei

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM-229010.

Keywords: LncRNA colon cancer-associated transcript 2 (CCAT2), endometrial cancer, miR-216b, Bcl-2, PTEN/PI3K/AKT and mTOR signaling pathways

DOI: 10.3233/CBM-170388

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 123-133, 2018

Authors: Li, Qi-Cai | Xu, Haiyan | Wang, Xiaohui | Wang, Ting | Wu, Jiang

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear. Recently, increasing evidence has suggested decreased expression of miR-34a is observed in a number of cancer types, including human osteosarcoma, and decreased miR-34a is involved in drug resistance. However, the underlying molecular mechanisms of decreased miR-34a on cisplatin chemoresistance in osteosarcoma has not been reported. METHODS: Osteosarcoma U2OS cells were transfected with miR-34a mimics for 48 h, then the cells were …treated with 3.0 μ m cisplatin for 24 h. Using siRNA targeting c-Myc and Bim to examine the relation between miR-34a, c-Myc and Bim expression exposure to cisplatin on cisplatin-induced apoptosis. RESULTS: Treatment of U2OS cells with cisplatin induced cell apoptosis by upregulation of c-Myc -dependent Bim expression; Osteosarcoma U2OS cells transfected with miR-34a mimics (miR-34a/U2OS) induced cell apoptosis and inhibited cell survival, and increased the sensitivity of U2OS cells to cisplatin. U2OS cells transfected with miR-34a mimics upregulated the protein expression of c-Myc and Bim. Targeting c-Myc downregulated the expression of Bim in the miR-34a/U2OS cells. In addition, Targeting Bim reversed the chemeresistance of miR-34a/U2OS cells to cisplatin. CONCLUSIONS: Our data indicated that miR-34a enhanced the sensitivity to cisplatin by upregulation of c-Myc and Bim pathway. Show more

Keywords: Osteosarcoma, chemotherapy, cisplatin, miR-34a, c-Myc, Bim

DOI: 10.3233/CBM-170452

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 135-144, 2018

Authors: Luo, Lan | Xu, Lina | Tang, Liang

Article Type: Research Article

Abstract: Endometrial carcinoma (EC) is a common malignant tumor in gynecology. Its incidence and development are closely associated with the levels of estrogenic and progesterone hormone. Extracellular signal-regulated kinase (ERK) signaling pathway abnormity is associated with a variety of tumors. This study detected estrogen receptor (ER), progesterone receptor (PR), ERK1, and ERK2 expression in EC and analyzed their correlations. A total of 40 EC patients in our hospital were selected as test group, while another 40 healthy volunteers were enrolled as control group. ER, PR, ERK1, and ERK2 expression in EC tissue, para-carcinoma tissue, and normal endometrial tissue were detected by …immunohistochemistry and Western blot. The positive rate of ER, PR, ERK1, and ERK2 in the test group was 50%, 40%, 60%, and 65%, respectively, which were significantly higher than those in the control (P < 0.05). ER, PR, ERK1, and ERK2 protein expressions in EC cell were significantly higher than those in the control (P < 0.05). ERK1 and ERK2 presented positive correlation with ER and PR (P < 0.05). In conclusion, EC patients presented higher expressions of ER, PR, which were correlated with higher levels of ERK1 and ERK2, suggesting they might be involved in the pathogenesis of EC. Show more

Keywords: Endometrial carcinoma, ER, PR, ERK1, ERK2

DOI: 10.3233/CBM-170457

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 145-149, 2018

Authors: Lian, Dongbo | Amin, Buhe | Du, Dexiao | Yan, Wei

Article Type: Research Article

Abstract: This paper aimed to probe into the expression of long non-coding RNA (lncRNA) SNHG16 in human gastric cancer (GC) and its potential tumor biological functions. The expression of lncRNA SNHG16 was detected in GC and adjacent tissues and GC cell lines using qRT-PCR. GC MGC-803 cells were transfected with siRNA of lncRNA SNHG16, as well as blank and negative control. A series of experiments including CCK-8, flow cytometry, transwell, and wound healing assay were adopted to evaluate the effects of lncRNA SNHG16 on cell growth and metastasis. Besides, the nude mouse xenograft tumor model was established to draw tumor growth …curve and measure tumor volume during treatments. TUNEL staining was used to determine the apoptosis rate of tissues. The expression of lncRNA SNHG16 in GC tissue, significantly associated with invasion depth, lymph node metastasis, TNM stage and histological differentiation (all P < 0.05), was upregulated compared with adjacent tissues. Transfected with siRNA of lncRNA SNHG16 inhibited GC MGC-803 cell proliferation, and arrested cells in the G0/G1 phase, and then promoted apoptosis rate with reduced cell invasion and shortened migration distance. Additionally, the nude mice xenograft presented lower tumor growth rate and weight loss alongside elevated apoptosis rate of tumor tissues. LncRNA SNHG16 is highly expressed in GC, while suppression of SNHG16 expression can inhibit proliferation, weaken invasion and migration of GC cells, and enhance apoptosis, to be a novel target for GC clinical treatment. Show more

Keywords: Long non-coding RNA SNHG16, gastric cancer, clinicopathological features, proliferation, migration, invasion, apoptosis, cell cycle

DOI: 10.3233/CBM-170462

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 151-160, 2018

Authors: Lu, Nanhang | Wang, Jinzeng | Zhu, Bijun | Zhang, Miaomiao | Qi, Fazhi | Wang, Xiangdong | Gu, Jianying

Article Type: Research Article

Abstract: BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease with a complex genetic etiology. Although three causative genes (PTCH1, PTCH2, SUFU) have been identified through linkage analysis and Sanger sequencing, the genetic background of NBCCS hasn’t been fully understood. METHODS: We performed a whole-exome sequencing (WES) in a Han Chinese NBCCS family and two unaffected volunteers to search for its causative gene. Bioinformatic analysis was used to select candidate genes and analyze the functional networks of each candidate gene. RESULTS: A total of 8 single-nucleotide variants (SNVs) were detected …in PTCH1, PTCH2 and SUFU in all the 5 subjects, however none of them was considered the pathogenic genetic mutation in this NBCCS family. The following filtering process identified 17 novel candidate genes (GBP3, AMPD1, ASPM, UNC5C, RBM46, HSPA1L, PNPLA1, GPR126, AP5Z1, ZFHX4, KIF24, C10orf128, COX15, GPRC5A, UGGT2, RHBDF1, RPUSD1). Among them ZFHX4 had been already identified as a new basal cell carcinoma susceptibility loci through a genome-wide association study (GWAS) and was considered the most likely pathogenic gene for this NBCCS family. The functional network analysis revealed that ZFHX4 may be involved in notch signaling pathway. CONCLUSIONS: Our study reported the identification of 17 novel candidate genes in a Han Chinese family through WES. ZFHX4 may be a susceptibility gene for NBCCS in Chinese population. Show more

Keywords: Gorlin syndrome, nevoid basal cell carcinoma syndrome, whole exome sequencing, Single-nucleotide variants, ZFHX4

DOI: 10.3233/CBM-170541

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 161-168, 2018

Authors: Zhao, Xiaoliang | Wen, Xiaohua | Wei, Wei | Su, Yanjun | You, Jian | Gong, Liqun | Zhang, Zhenfa | Wang, Meng | Xiao, Jianyu | Wei, Xiyin | Wang, Changli

Article Type: Research Article

Abstract: BACKGROUND: Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. OBJECTIVE: To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. METHODS: We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. RESULTS: Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p = 0.76), respectively. The clinical benefit …(CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. CONCLUSION: Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC. Show more

Keywords: RH-endostatin, non-small cell lung cancer, predictor, circulating endothelial progenitor cells, perfusion imaging

DOI: 10.3233/CBM-170565

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 169-177, 2018

Authors: Zhang, Suxia | Wang, Min | Li, Qirong | Zhu, Ping

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

Keywords: miR-101, PI3K/Akt/mTOR, apoptosis, invasion, proliferation, endometrial cancer

DOI: 10.3233/CBM-170620

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 179-186, 2018

Authors: Hou, Li | Hou, Xiaofei | Wang, Lijing | Li, Zenghui | Xin, Beibei | Chen, Jing | Gao, Xiaofei | Mu, Haixia

Article Type: Research Article

Abstract: BACKGROUND: The study was aimed at investigating the role of PD98059 on impairing the cisplatin-resistance of ovarian cancer cells and figuring out the potential mechanism. MATERIAL AND METHODS: Treated with low dose of cisplatin (DDP), DDP-resistant ovarian cancer cells were built and named as SKOV-3/DDP. The cell viabilities of ovarian cancer cell line SKOV-3 and SKOV-3/DDP were detected using MTT assay. Wound healing assay and flow cytometry were performed to detect the migratory ability and cell cycle variation of the two cells and assess the sensibility to DDP in the two cell lines. However, cotreated with DDP …and PD98059, cell viability, migration and cell cycle of SKOV-3/DDP were determined again. The DDP-resistance varied a lot and the potential mechanism was studied via western blot assay. RESULTS: Both treated with DDP, SKOV-3/DDP showed an intense resistance than SKOV-3 including stronger cell viability, larger migration area and less G1/G0 arrest, which confirmed the successfully established DDP-resistant cell line. The phosphorylation of ERK and the activation of epithelial mesenchymal transition (EMT) process contributes to the enhanced resistance. PD98059, a MEK inhibitor, suppresses the ERK pathway and the EMT process of SKOV-3/DDP. Co-treated by DDP and PD98059, cell proliferation and migratory area decreased, meantime more cell were arrested in G0/G1 phase compared to simple treatment of DDP or PD98059. CONCLUSION: PD98059 efficiently impairs the DDP-resistance of ovarian cancer cells via downregulating the ERK pathway and the EMT process. Show more

Keywords: Ovarian cancer, cisplatin resistance, epithelial mesenchymal transition, ERK pathway

DOI: 10.3233/CBM-170644

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 187-194, 2018

Authors: Hu, Xiao-Yan | Liu, Zhe | Zhang, Kai-Lin | Feng, Jing | Liu, Xiao-Fang | Wang, Ling-Yun | Wang, Zi-Wei

Article Type: Research Article

Abstract: N-myc downstream regulated gene 2 (NDRG2) is frequently down-regulated in various cancers and functions as a candidate tumor suppressor gene. NDRG2 has been shown to be SUMOylated on the lysine 333 residue, which promoted its ubiquitination and sequentially degradation by the SUMO-targeted ubiquitin E3 ligase RNF4. However, how to regulated NDRG2 deSUMOylation process remains largely unknown. Here, we report that Sentrin/SUMO specific protease (SENP2) was down-regulated in clinic gastric cancer samples and possessed a tumor-suppressive role in gastric cancer. At the molecular level, we found that SENP2 interacts with NDRG2 and mediates the de-SUMOylation process of NDRG2. Overexpression of SENP2 …stabilized NDRG2, whereas silencing SENP2 caused rapid NDRG2 SUMOylation and degradation, indicating SENP2 antagonizes NDRG2 ubiquitination and degradation, thereby promoting the stability and function of this protein. Thus, our study reveals that SENP2 acts as a tumor suppressor which is deregulated in gastric cancer and the specific de-SUMOylation activity of SENP2 for NDRG2 is critical for it stabilization as well as gastric cancer cells proliferation. Show more

Keywords: SENP2, NDRG2, gastric cancer, SUMOylation

DOI: 10.3233/CBM-170651

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 195-201, 2018

Authors: Sun, Jiachun | Wang, Dengkui | Li, Xiangming | Yan, Junqiang | Yuan, Xiaozhi | Wang, Wei

Article Type: Research Article

Abstract: OBJECTIVE: Glioma-associated oncogene homolog 1 (Gli1 ) in Hedgehog signal pathway regulates Cyclin D1 expression, cell cycle or proliferation modulation. Esophageal cancer patients had significantly elevated Gli1 expression, which is related with survival and prognosis. It has been demonstrated that the level of miR-150 was decreased in esophageal cancer patients compared to normal control. As a complementary relationship exists between miR-150 and 3’-UTR of Gli1 , this study investigated if miR-150 played a role in regulating Gli1 expression, and proliferation or cell cycle of esophageal cancer cells. PATIENTS AND METHODS: Esophageal squamous cell carcinoma (ESCC) …patients from our hospital were recruited to collect tumor and adjacent tissues for miR-150 and Gli1 expression. Esophageal carcinoma cell line EC9706 and normal esophageal epithelial cell line HEEC were compared for expression of miR-150, Gli1 and Cyclin D1 . Dual luciferase reporter gene assay examined the targeted relationship between miR-150 and 3’-UTR of Gli1 . In vitro cultured EC9706 cells were treated with miR-150 mimic, si-Gli1 or the combination of miR-150 mimic and si-Gli1, respectively, to check their gene expression, cell cycle and proliferation. RESULTS: ESCC tissues had significantly higher Gli1 expression and lower miR-150 expression. EC9706 cell also had higher Gli1 expression than that in HEEC, whilst miR-150 was down-regulated. Via targeting 3’-UTR of Gli1 gene, miR-150 inhibited its expression. Transfection of miR-150 mimic, si-Gli1 or the combination of miR-150 mimic and si-Gli1, respectively, remarkably decreased expression of Gli1 and Cyclin D1 expression in EC9706 cells, whose cell cycle arresting at G0/G1 phase was enhanced with weakened proliferation. CONCLUSIONS: MiR-150 can induce G0/G1 cell cycle arresting and weaken proliferation of esophageal carcinoma cells via targeted inhibition on Gli1 and downstream expression of Cyclin D1 . Show more

Keywords: MicroRNA-150, Gli1, Cyclin D1, cell proliferation, cell cycle, esophageal carcinoma

DOI: 10.3233/CBM-170658

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 203-210, 2018

Authors: Yang, Ching-Yao | Lin, Mong-Wei | Chang, Yih-Leong | Wu, Chen-Tu

Article Type: Research Article

Abstract: BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). METHODS: The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients …with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. RESULTS: Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. CONCLUSIONS: Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment. Show more

Keywords: Cancer vaccine, Globo H, immunotherapy, non-small cell lung cancer, tumor-associated carbohydrate antigen

DOI: 10.3233/CBM-170660

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 211-220, 2018

Authors: Huang, Tonghai | Wang, Guangsuo | Yang, Lin | Peng, Bin | Wen, Yuxin | Ding, Guanggui | Wang, Zheng

Article Type: Research Article

Abstract: BACKGROUND: Non-small cell lung cancer (NSCLC) is the main type of lung cancer. While miR-186 is significantly reduced in lung cancer tissues and cells, its role in NSCLC has not been completely elucidated. MATERIAL AND METHODS: We used qRT-PCR and western blot methods to investigate the levels of miR-186 and YY1 in 21 pairs of NSCLC tissues. Dual luciferase reporter gene assays were performed to detect whether miR-186 directly targets YY1 . Next, the roles of miR-186 and its target gene (YY1 ) in determining the proliferation, apoptosis and migration capabilities of selected cell lines (A549 and HCC827) …were investigated by using miR-186 mimics or YY1 siRNA. RESULTS: Our results showed that miR-186 was downregulated and YYI was upregulated in NSCLC tissue, and miR-186 expression was negatively associated with YY1. Similarly, miR-186 was also downregulated and YY1 expression also was upregulated in both A549 and HCC827 cells; furthermore, miR-186 was found to directly target YY1 . Cell proliferation, invasion, and migration, as well as apoptosis induction were more strongly inhibited by YY1 siRNA than by miR-186. CONCLUSION: Our results suggest that miR-186 and its target gene (YY1 ) could possibly serve as new prognostic biomarkers and therapeutic targets for treating NSCLC in humans. Show more

Keywords: miR-186, YY1, cell proliferation, apoptosis, migration and invasion, non-small cell lung cancer

DOI: 10.3233/CBM-170670

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 221-228, 2018

Authors: Feferman, Leo | Deaton, Ryan | Bhattacharyya, Sumit | Xie, Hui | Gann, Peter H. | Melamed, Jonathan | Tobacman, Joanne K.

Article Type: Research Article

Abstract: BACKGROUND: Arylsulfatase B (ARSB) removes the 4-sulfate group from chondroitin 4-sulfate (C4S) and dermatan sulfate and is required for their degradation. Prior work showed that ARSB immunohistochemical scores were lower in malignant prostate tissue, and were associated with higher Gleason scores and recurrence. OBJECTIVE: This study aims to confirm that ARSB immunostaining of prostate tissue obtained at the time of radical prostatectomy is prognostic for prostate cancer recurrence. METHODS: Intensity and distribution of ARSB immunostaining were digitally analyzed in a large, well-annotated, prostate cancer tissue microarray (TMA). Scores were calculated for stroma and epithelium and compared …for 191 cases, including 36 recurrences, defined as PSA > 0.2 ng/ml. RESULTS: Epithelial scores were significantly lower in the recurrences (p = 0.010), and among subgroups with age > 60, initial PSA > 6 ng/ml, or Gleason grade = 7. ARSB score did not improve the prediction of recurrence in multifactorial analysis. CONCLUSIONS: Study findings validate previous findings and provide further evidence that lower ARSB is associated with prostate cancer recurrence. Additional studies are required to assess if there are specific cutoff values that may help predict recurrence. Show more

Keywords: Sulfatase, chondroitin sulfate, versican, immunohistochemistry, glycosaminoglycans, N-acetylgalactosamine-4-sulfatase

DOI: 10.3233/CBM-170680

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 229-234, 2018

Authors: Bakhti, Seyedeh Zahra | Latifi-Navid, Saeid | Zahri, Saber | Bakhti, Fatemeh Sadat | Hajavi, Naser | Yazdanbod, Abbas

Article Type: Research Article

Abstract: BACKGROUND: Although the most extensive studies revealed the role of H. pylori VacA and CagA toxins in the development of gastric adenocarcinoma, the magnitude of this association and the correlations of vacA mosaicism and cagA status with cardia gastric adenocarcinoma (CGA) still remain controversial. OBJECTIVE: We aimed to examine the linkage of H. pylori highly cytotoxic genotypes to CGA in Iranian populations as a model. METHODS: A total of 601 Iranian patients were enrolled. Biopsies were cultured, genotyped, and anatomically and histologically classified. RESULTS: The vacA …c1 genotype, but not cagA status, showed a strong association with the risk of both CGA and non-cardia adenocarcinoma (NCGA), whether the controls were non-tumors, as those with either non-atrophic gastritis or peptic ulcerations, (the OR (95%CI) was 14.11 (4.91–40.52) and 9.59 (4.06–22.65), respectively) or those with NAG (the OR (95%CI) was 10.71 (3.49–32.82) and 8.11 (3.26–20.16), respectively). The vacA c1/cagA + genotype was significantly associated with an increased risk of NCGA, whether the controls were non-tumors or those with NAG; the adjusted risk was 4.706 (1.41–15.67) and 4.85 (1.42–16.51), respectively. CONCLUSIONS: The H. pylori vacA c1 genotype, but not cagA status, might be the first important bacterial biomarker for predicting the cardia adenocarcinoma risk in male patients aged ⩾ 55 in Iran. Show more

Keywords: Helicobacter pylori, vacA c, cagA, cardia gastric adenocarcinoma, diffuse-type gastric adenocarcinoma, intestinal-type gastric adenocarcinoma

DOI: 10.3233/CBM-170701

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 235-246, 2018

Authors: Sun, Yun-Peng | Wang, Xuan | Gao, Yong-Sheng | Zhao, Song | Bai, Yang

Article Type: Research Article

Abstract: In large autopsy series, the estimated frequency of primary tumors of the heart ranges from 0.0017% to 0.33%. Approximately 25% of primary cardiac tumors are malignant, and nearly 20% of these are sarcomas. To date, a completely feasible surgical resection remains the major treatment measure of cardiac sarcoma, especially for recurrent focal cardiac sarcoma and the recurrence of a restrictive metastasis. Although characteristically medical treatments are recommended, there is no consistent opinion for adjuvant radiotherapy and chemotherapy following an operation. Since these tumors usually undergo extensive spread by the time that the diagnosis is established, the prognosis of cardiac sarcoma remains poor. …In this report, we described a case who underwent initial cardiac tumor resection, and was confirmed to be a pleomorphic undifferentiated sarcoma based on pathological findings. However, the patient complicated with cerebral infarction and subsequent brain metastasis sarcoma after the initial surgery, which was confirmed by brain tissue pathology. During the course of therapy, the patient underwent three surgical operations and refused to accept any chemotherapy and radiotherapy intervention. To the best of our knowledge, this is the first case report describing a primary cardiac sarcoma complicated with cerebral infarction and brain metastasis. The management of primary cardiac sarcoma is also discussed. Show more

Keywords: Primary cardiac sarcoma, cerebral infarction, brain metastasis

DOI: 10.3233/CBM-170448

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 247-250, 2018