Cancer Biomarkers - Volume 22, issue 4

Authors: Zhou, Jian | Ge, Yuyuan | Hu, Yun | Rong, Dawei | Fu, Kai | Wang, Hanjin | Cao, Hongyong | Tang, Weiwei

Article Type: Other

Abstract: Circular RNAs (circRNAs), which were discovered as a special class of endogenous non-coding RNAs, have recently shown huge capabilities as gene regulators in different species in a wide variety of organisms including viruses, plants, archaea and animals. These circRNAs mainly arise from exons or introns in different combinations by special selective splicing and are enriched in cytoplasm. Apart from that, circRNAs usually display patterns of cell-type, tissue-type and developmental-stage specific expression in eukaryotic transcriptome. These findings hint at the vital function of circRNAs in development and diseases. Herein, we summarize the current understanding of the molecular characteristics of circRNAs and …discuss their proposed functions and mechanism-of-action in human diseases, animals as well as botanics. Show more

Keywords: Circular RNA, anti-cancer, diagnosis, botanics, animals

DOI: 10.3233/CBM-181296

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 597-610, 2018

Authors: Shakya, Manjul | Zhou, Aijun | Dai, Danian | Zhong, Qian | Zhou, Zhongguo | Zhang, Yaojun | Li, Xu | Bholee, Ashwin Kumar | Chen, Minshan

Article Type: Research Article

Abstract: BACKGROUND: Transforming acidic coiled-coil protein 2 (TACC2) is a member of TACC family proteins which is mainly involved in the stabilization of spindles and regulation of microtubule dynamics through interactions with molecules involved in centrosomes/microtubules. TACC2 is involved in tumorigenesis of variety of cancers but the clinical significance of TACC2 protein in hepatocellular carcinoma (HCC) is still unclear. OBJECTIVE: This study aims to investigate the expression of TACC2 in HCC and determine if clinical significance and prognostic relevance exists. METHODS: We performed quantitative PCR (qPCR) and western blot to examine TACC2 mRNA and …protein expression in paired HCC tissues and matched adjacent non-cancerous tissues. Immunohistochemistry was performed in 106 postoperative HCC samples. RESULTS: There was higher expression of TACC2 protein and mRNA in HCC tissue. Immunohistochemistry analysis showed high expression of TACC2 in HCC tissue and was significantly associated with the capsular extension, tumor recurrence and shortened overall and disease free survival. The Cox regression analysis suggested that a high expression of TACC2 was an independent prognostic factor for HCC patients. CONCLUSION: This finding suggests that TACC2 may be a useful tool as a candidate biomarker to predict the recurrence and prognosis of HCC. Show more

Keywords: Transforming acidic coiled-coil protein 2, hepatocellular carcinoma, prognosis, survival

DOI: 10.3233/CBM-170091

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 611-619, 2018

Authors: Liu, Hongqian | Cao, Bofeng | Zhao, Yuanyuan | Liang, Haijing | Liu, Xinfeng

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVES: MicroRNA (miR-221/222) is frequently overexpressed in many cancers and is associated with poor prognosis. However, the role of miR-221/222 in retinoblastoma (RB) remains unclear. This study aimed to detect the clinical significance of miR-221/222 in RB patients and explore its role in RB cells in vitro . METHODS: Expression of miR-221/222 was assessed in fresh RB tissue collected from 64 eyes and normal retinal tissues from 18 unrelated donor cadaver eyes by quantitative real time RT-PCR analysis (qRT-PCR), and correlated with the histopathological findings. Human RB Y79 cells were transfected with miR-221/222 precursors …or inhibitors to overexpress or downregulate miR-221/222 expression, respectively, using Lipofectamine 2000 reagent. The biological effects of miR-221/222 were then assessed by cell viability assays, colony formation assays, apoptosis detection assays, Matrigel ® invasion assays, and wound-healing assays. RESULTS: Higher miR-221/222 expression was detected in RB tissues compared to that of the normal retinal tissues (p < 0.001). Higher miR-221/222 expression was correlated with invasion in patients with RB. Targeting of miR-221/222 induced apoptosis and inhibited Y79 cell proliferation, migration, and invasion in vitro . However, overexpression of miR-221/222 promoted Y79 cell proliferation, migration, and invasion in vitro . CONCLUSIONS: Overexpression of miR-221/222 was associated with tumor invasiveness in patients with RB. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. Show more

Keywords: Retinoblastoma, miR-221/222, marker, invasion

DOI: 10.3233/CBM-170721

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 621-629, 2018

Authors: Wang, Shanshan | Cui, Shichang | Zhao, Wenming | Qian, Zhiling | Liu, Hui | Chen, Yuhan | Lv, Fudong | Ding, Hui-Guo

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNAs) play an important role in pathogenesis and development of hepatocellular carcinoma (HCC). However, circRNA expression profiles in hepatitis B Virus (HBV)-related HCC remain to be studied. METHODS: Total 13 HBV-related HCC patients were enrolled for study. Three HCC and 3 paired adjacent non-tumorous (NT) tissues from 3 patients were performed for microarray. Ten pairs of HCC tissues were used to verify the identified up-regulated and down-regulated circRNAs obtained from the microarray data by quantitative real-time reverse transcription PCR (qRT-PCR). Total RNA was isolated and treated with Rnase R to remove linear RNA, then hybridized to …the array to screen for circRNAs. Bioinformatics analyses including clustering, differential expression, annotation of circRNA/microRNA (miRNA) interactions, Go analysis and KEGG pathway analysis, were performed. RESULTS: Based on the microarray data, we found significantly up-regulation of 24 circRNAs and down-regulation of 23 circRNAs in the HCC samples compared to NT samples (fold change ⩾ 2.0 and P < 0.05). Of them, 6 candidate circRNAs (hsa_circRNA_102814, 100381, 103489, 101764, 100327, and 103361) were verified by qRT-PCR. Of them, hsa_circRNA 100381, 103489 up-regulation and 101764 down-regulation were found to be significantly different in the 10 validation HCC tissue. Clusters of circRNAs were aberrantly expressed in HCC compared with NT samples. CircRNA_101764 was the largest nodes in circRNA/microRNA co-expression network, especially co-expression with hsa-miR-181 family, which plays an important role in cell network. Annotation of circRNA/miRNA interactions indicated that the biological effects of circRNA may be achieved by binding of miRNAs. GO analysis revealed that numerous target genes were involved in the biological processes, cellular component and molecular function. There was nearly 30 target genes enrichment on KEGG pathways analysis, PI3K-Akt signaling pathway which the most number of genes involved. CONCLUSION: In this study, we comprehensively explored the expression of differentially expressed circRNAs in HBV-related HCC, and our results indicate that circRNA_101764 may play an important role in the development of HCC. Show more

Keywords: Hepatocellular carcinoma, HBV, circular RNA, microarray

DOI: 10.3233/CBM-170910

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 631-640, 2018

Authors: Gao, Jie | Shao, Zhongjun | Yan, Min | Fu, Ting | Zhang, Lei | Yan, Yongping

Article Type: Research Article

Abstract: STAT3 is an important molecule in Janus kinase (JAK) signal transducer and activator of transcription (STAT) signal pathway, and facilitates expression of various oncogenic genes such as Bcl-2, thus is correlated with tumor onset, progression and drug resistance. MiR-29a down-regulation is associated with the pathogenesis of nasopharyngeal carcinoma. Bioinformatics analysis demonstrated a complementary binding between miR-29a and 3’-UTR of STAT3. This study aims to investigate the role of miR-29a in regulating STAT3, as well as in Taxol resistance of nasopharyngeal carcinoma CNE-1 cells. Dual luciferase reporter gene assay showed a regulatory relationship between miR-29a and STAT3. Rhodamine 123 repository in …CNE-1 and CNE1/Taxol drug resistant cells was measured together with the expression of miR-29a, STAT3, and p-STAT3. Flow cytometry was used to measure cell apoptosis and PCNA expression under Taxol treatment. CNE-1/Taxol cells were treated with miR-29a mimic and or si-STAT3, followed by measuring the expression of miR-29a, STAT3, and p-STAT3 and cell apoptosis. CCK-8 assay was performed to evaluate cell proliferation. MiR-29a inhibited STAT3 expression. Significantly lower Rhodamine 123 repository, miR-29a expression and apoptosis and higher expression of STAT3, p-STAT3 and PCNA were observed in CNE-2/ Taxol cells than those in CNE-1 cells. Transfection of miR-29a mimic and/or si-STAT3 decreased STAT3, p-STAT3 and PCNA expression, inhibited proliferation and promoted cell apoptosis. MiR-29a down-regulation is correlated with drug resistance of nasopharyngeal carcinoma cell line CNE-1 and MiR-29a up-regulation decreases Taxol resistance of nasopharyngeal carcinoma CNE-1 cells possibly via inhibiting STAT3 and Bcl-2 expression. Show more

Keywords: MiR-29a, STAT3, taxol, nasopharyngeal carcinoma, drug resistance

DOI: 10.3233/CBM-170964

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 641-648, 2018

Authors: Liu, Chen-Guang | Cui, Xiao-Long | Wei, Zhi-Gang | Guo, Jian-Sheng

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer is one of the most common malignant tumours. Identifying novel genes that govern the development of gastric cancer will help to elucidate its molecular mechanisms and find novel biomarkers. METHODS: Expression of the ANKRD49 protein was assessed by immunohistochemical analysis of tissue microarrays containing 92 sets of human gastric cancer specimens with adjacent non-cancerous tissue. Associations between ANKRD49 levels and clinicopathological characteristics of the patient were investigated. The correlation between ANKRD49 expression and patient survival was analysed by the Kaplan-Meier method. RESULTS: The results revealed that the expression level of the …ANKRD49 protein in gastric cancer was significantly upregulated and correlated with the tumour size, tumour-node-metastasis (TNM) stage, histological grade, depth of invasion, vessel invasion, lymph node metastasis and distant metastasis. The mean survival time of patients with low expression levels of ANKRD49 was significantly longer than that of patients with high expression levels of ANKRD49. Multivariate Cox regression analysis demonstrated that the ANKRD49 protein expression level was an independent prognostic indicator for the survival rate of patients with gastric cancer. CONCLUSION: The results of the present study highlighted an important role of the ANKRD49 protein in the progression of gastric cancer. The ANKRD49 protein could act as a potential biomarker for prognosis evaluation of gastric cancer and may be used as a molecular target for gastric cancer treatment. Show more

Keywords: ANKRD49, gastric cancer, tissue microarray, immunohistochemistry, prognosis

DOI: 10.3233/CBM-171074

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 649-656, 2018

Authors: Mlak, Radosław | Powrózek, Tomasz | Brzozowska, Anna | Homa-Mlak, Iwona | Mazurek, Marcin | Małecka-Massalska, Teresa

Article Type: Research Article

Abstract: BACKGROUND: Intensified treatment of head and neck cancers (HNC): by radiotherapy (RTH) commonly combined with cytotoxic drugs is associated with oral mucositis (OM). Changes in the functioning of nucleotide synthesis pathway (RNR1, coded by RRM1 gene) can modulate the efficiency of cellular DNA repair mechanisms and influence the risk of occurrence and severity of OM in HNC patients after RTH. OBJECTIVE: The objective of this study was to evaluate the correlation between expression of RRM1 gene measured in free circulating RNA (cfRNA) and the risk of more severe OM and disease-free survival (DFS) and …overall survival (OS) in patients undergoing RTH for HNC. METHODS: The study included 60 patients treated with RTH for HNC. RRM1 gene expression was examined in circulating RNA isolated from peripheral blood plasma (before treatment). RESULTS: High RRM1 gene expression was significantly associated with higher risk of grade 3 OM after 5 (OR = 4.97), 6 (OR = 4.33) and 7 (OR = 3.50) weeks of RTH. Expression of RRM1 gene was not significantly related with risk of DFS and OS shortening (however well separated Kaplan-Meier curves might suggest its potential prognostic impact). CONCLUSIONS: The evaluation of RRM1 gene expression in cfRNA allows for estimation of the risk of severe OM in patients subjected to RTH. Show more

Keywords: cfRNA, DNA repair, head and neck cancer, liquid biopsy, oral mucositis, radiotherapy, RRM1, survival

DOI: 10.3233/CBM-171082

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 657-667, 2018

Authors: Shu, Jian | Yu, Hanjie | Du, Haoqi | Zhang, Jiaxu | Zhang, Kun | Li, Xiaojie | Xie, Hailong | Li, Zheng

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Gastric cancer (GC) is a common and fatal malignancy with a worldwide occurrence. There still lacks effective biomarkers for precisely evaluating GC. Saliva is a biological fluid with enormous diagnostic potentials which emerged many advantages. We aimed to discover the novel biomarkers for accurately distinguishing early GC based on saliva glycopatterns. METHODS: We used Aleuria Aurantia Lectin (AAL)-magnetic particle conjugates to isolate fucosylated glycoproteins in the pooled saliva of healthy volunteers (HV, n = 51) and patients with atrophic gastritis (AG, n = …51) or GC (n = 51), following to release the N - and O -linked glycans from the isolated proteins with PNGase F and NaClO, and further identified the released glycans by MALDI-TOF/TOF-MS, respectively. RESULTS: A total of 9/9, 8/11, and 9/9 fucosylated N -/O -linked glycans were annotated in the isolated salivary proteins from HV, AG, and GC, respectively. Among these, six fucosylated N -linked glycansand four O -linked glycans exhibited significantly increased expression levels in GC, while five fucosylated N -linked glycans and ten fucosylated O -linked glycans exhibited significantly decreased expression levels in GC. The proportion of fucosylated N -linked glycans was decreased in GC (41.66%) compared with AG (43.63%) and HV (52.57%), as well as the fucosylated O -linked glycans was apparently decreased in GC (19.58%) compared with AG (25.43%) and HV (55.54%). CONCLUSIONS: This study could provide pivotal information to distinguish among HV, AG, and GC, and facilitate the discovery of biomarkers for GC diagnosis based on precise alterations of N - and O -linked glycans in saliva. Show more

Keywords: Saliva, gastric cancer, MALDI-TOF/TOF-MS/MS, N- and O-Linked glycan

DOI: 10.3233/CBM-171087

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 669-681, 2018

Authors: Wang, Lijun | Wu, Qi | Zhu, Shan | Li, Zhiyu | Yuan, Jingping | Liu, Lin | Yu, Dehua | Xu, Zhiliang | Li, Juanjuan | Sun, Shengrong | Wang, Changhua

Article Type: Research Article

Abstract: DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The prognostic value of DNER in prostate cancer has not been evaluated. Here we showed that the up-regulation of DNER protein was observed in prostate cancer detected by immunohistochemistry (IHC) and quantum dot-based immunofluorescent imaging and quantitative analytical system (QD-IIQAS). However, a higher accuracy of measurements of DNER expression in prostate cancer was found by QD-IIQAS than by IHC (AUC = 0.817 and 0.617, respectively). DNER was significantly higher in patients undergoing bone metastasis (P = 0.045, RR …= 3.624). In addition, DNER overexpression was associated with poor overall survival (OS) (P = 0.028, adjusted HR = 8.564) and recurrence-free survival (RFS) (P = 0.042, adjusted HR = 3.474) in patients suffering prostate cancer. Thus, QD-IIQAS is an easy and accurate method for assessing DNER and the DNER expression was an independent prognostic factor in prostate cancer. Show more

Keywords: Quantum dot-based immunofluorescent imaging, DNER, prognostic value, prostate cancer

DOI: 10.3233/CBM-171107

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 683-691, 2018

Authors: Liu, Dengxiang | Wang, Na | Sun, Yawei | Guo, Ting | Zhu, Xiaoyan | Guo, Jun

Article Type: Research Article

Abstract: OBJECTIVE: To analysis the expression of VEGF in gastric carcinoma cell and tumor tissue, our study determined the relationship between the expression of VEGF and tumor incidence, metastasis and prognosis in human gastric carcinoma. METHODS: Treatment of ZD6474 at dose of 30 μ mol/L was performed in gastric carcinoma cell BGC823. qPCR and Western-blot were used to analysis the mRNA and protein expression of VEGF. MTT, wound healing and Transwell experiments were conducted to study the effect of VEGF on tumor incidence, metastasis and prognosis. Sixty patients with gastric cancer were selected as the gastric …cancer group, and 30 patients with gastric ulcer receiving main gastric resection were selected as control group. The survival curve of patients with gastric cancer in five years was recorded. The correlation between expression of VEGF to incidence, metastasis and prognosis of gastric cancer was evaluated by Cox multifactor regression. RESULTS: The mRNA and protein expression of VEGF in treatment group were significantly lower than that of control group (P < 0.01). The results of MTT, wound healing and Transwell experiments were showed that the cell proliferation, migration and invasion capacity in treatment group were significantly reduced compared to that of the control group (P < 0.01). The 5-year survival rate for patients with VEGF positive expression was significantly decreased compared to the patients with VEGF expression negative (P < 0.01). The tumor size, differentiation, lymph node metastasis and tumor stage were statistically related to VEGF level (P < 0.05). The results of Cox regression multifactor analysis showed that lymph node metastasis, tumor staging and the expression of VEGF were significantly associated to the prognosis of gastric cancer patients (P < 0.05). CONCLUSION: Our data demonstrated that the expression of VEGF was significantly related to the tumor incidence, metastasis and prognosis of patients with gastric cancer, which provides new leads to the diagnosis of gastric cancer. Show more

Keywords: Gastric carcinoma, VEGF, prognosis, metastasis

DOI: 10.3233/CBM-171163

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 693-700, 2018

Authors: Lyu, Yunxiao | Cheng, Yunxiao | Wang, Bin | Chen, Liang | Zhao, Sicong

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have shown that Sulfatase 1 (SULF1) plays a crucial role in the genesis, development, and progression of tumors. However, there have been few studies on the role of SULF1 in pancreatic cancer. OBJECTIVE: The present study examined the differences in SULF1 expression levels between pancreatic cancer and normal tissues, and their correlation with the clinicopathological features and prognosis. METHODS: A total of 65 pancreatic cancer samples were enrolled in this study. An immunohistochemical assay were used in this study. The relationship between SULF1 expression and clinicopathological features were tested using …χ 2 test or Fisher’s exact test. The Kaplan-Meier method was used to calculate the cumulative survival rates of the patients. RESULTS: The study showed that the SULF1 expression level was higher in pancreatic cancer tissues than in normal tissues. Analysis of the clinical and pathological data of patients revealed that high SULF1 expression was associated with later T, N, and TNM stages, higher CA19-9 levels, smaller tumor size, and poorer prognosis. CONCLUSIONS: These findings suggested that SULF1 could be an indicator of the clinicopathological features and prognosis of pancreatic cancer. Show more

Keywords: Sulfatase 1, pancreatic cancer, metastasis, prognosis

DOI: 10.3233/CBM-181210

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 701-707, 2018

Authors: Taniguchi-Ponciano, Keiko | Ribas-Aparicio, Rosa María | Marrero-Rodríguez, Daniel | Arreola-De la Cruz, Hugo | Huerta-Padilla, Víctor | Muñoz, Nancy | Gómez-Ortiz, Laura | Ponce-Navarrete, Gustavo | Rodríguez-Esquivel, Miriam | Mendoza-Rodríguez, Mónica | Gómez-Virgilio, Laura | Peralta, Raúl | Serna, Luis | Gómez, Guillermo | Ortiz, Jorge | Mantilla, Alejandra | Hernández, Daniel | Hernández, Ángeles | Bandala, Cindy | Salcedo, Mauricio

Article Type: Research Article

Abstract: BACKGROUND: Similarities between the pathologic progression of cancer and the physiologic process of placentation have been recognized for many years proposing that both present similar mechanisms and processes. Cervical cancer (CC) is one of the most frequent neoplasia among Mexican women turning it into an important health problem. OBJECTIVE: The aim of this study was to determine the degree of the involvement of pregnancy related genes and in cancer progression by in-silico analysis and validated in CC samples. RESULTS: The data mining analysis resulted in the identification of genes expressed in term …placenta, first trimester placenta and normal cervical tissues. Finally, we selected KISS1 for the involvement of pregnancy related gene and also in cancer process. In order to explore KISS1 in CC, we analyzed Copy Number Variation (CNV) and gene expression using microarray experiments. KISS1 showed 20% genomic gain in 1q32.1 on CC samples. Furthermore, microarray analysis showed KISS1 as up-regulated genes. Results were validated showing an overexpression of 85% of KISS1 in CC samples. CONCLUSIONS: Data suggest KISS1 as a great candidate for CC molecular markers or as a therapeutic target for CC. Also, HPV presence does not seem to alter the KISS1 expression in CC. Show more

Keywords: KISS1, cervical cancer, in-silico analysis, molecular marker

DOI: 10.3233/CBM-181215

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 709-719, 2018

Authors: Wang, Yaozong | Li, Jianjun | Dai, Lei | Zheng, Jueru | Yi, Zhanbo | Chen, Liangliang

Article Type: Research Article

Abstract: BACKGROUND: Recurrence following conventional therapies in patients with breast cancer is a major cause of morbidity and mortality. This study aimed to investigate potential predictive biomarkers for breast cancer recurrence especially microRNAs (miRNAs). METHODS: The primary breast cancer patients who were scheduled to undergo curative resection in our hospital from May 2007 to May 2012 were recruited in this study. Clinical and pathological characteristics were compared in patients with or without recurrence. The expressions of tissue miRNAs by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) were also analyzed in patients with recurrence or not. Multivariate Cox analysis …was fit to evaluate potential predicative factors for breast cancer recurrence. Kaplan-Meier plots was conducted to further evaluate the association between miR-17-5p expression and recurrence-free survival (RFS). RESULTS: A total of 133 consecutive patients were enrolled into the final analysis and 29 of them have suffered recurrence within 5 years after the operation. Our results revealed tissue miR-17-5p expression as an independent risk factor for breast cancer recurrence (HR: 4.45; 95% CI: 1.58–11.53, P = 0.015). Patients with a higher miR-17-5p expression was significantly associated with a worse 5-year RFS by log-rank test (p = 0.017). CONCLUSIONS: This study suggested that miR-17-5p might be a useful predictive factor for breast cancer recurrence. Show more

Keywords: Breast cancer, recurrence, microRNA, prediction

DOI: 10.3233/CBM-181228

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 721-726, 2018

Authors: Liu, Yang | Li, Lin | Liu, Zheng | Yuan, Qingling | Lu, Xiubo

Article Type: Research Article

Abstract: BACKGROUNDS: The purpose of this study was to investigate clinical role and functional effects of miR-431 expression in papillary thyroid carcinoma (PTC). METHODS: Expression of miR-431 in PTC patient tissue samples and plasma samples was examined by using qRT-PCR methods. Cell migration and invasion capacity were evaluated using transwell assays. Western blot analysis was performed to detect protein expression after miR-431 overexpression in PTC cells. RESULTS: We demonstrated that miR-431 expression was lower in PTC tissues and plasma samples compared to their corresponding controls. MiR-431 expression was particularly lower in PTC patients with …lymph node (LN) metastasis. In vitro , miR-431 overexpression significantly inhibited cell migration, invasion and EMT process by upregulating E-cadherin and downregulating Vimentin expression. Additionally, wedemonstrated that miR-431 overexpression suppressed Hedgehog (Hh) signaling pathway by downregulating Gli1 expression. CONCLUSION: Our results indicated that miR-431 could serve as a predictor for PTC patients with positive lymph node metastasis and a potential target of PTC treatment. Show more

Keywords: Papillary thyroid carcinoma, miR-431, lymph node metastasis, cell invasion

DOI: 10.3233/CBM-181253

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 727-732, 2018

Authors: Faghih, Zahra | Deihimi, Safoora | Talei, Abdolrasoul | Ghaderi, Abbas | Erfani, Nasrollah

Article Type: Research Article

Abstract: To find out if the T cell repertoire is efficiently and specifically provoked in patients with breast cancer, we have investigated the clonotypes of main T cell subsets (based on Vβ -Chain) in tumor draining lymph nodes. CD4+ helper, CD8+ cytotoxic and (CD4+CD127 dim CD25+) regulatory T cells, were negatively selected, and isolated, from lymph node mononuclear cells of 14 untreated patients with breast cancer. Four non-malignant patients, who underwent surgical operation, were also recruited as the control group. Based on sequences and new nomenclature of the T cell Receptor β Variables (TRBVs) …available in the international ImMunoGeneTics (IMGT) database, 28 TRBV specific forward primers and two TRB Constant region (TRBC) specific reverse primers were developed to amplify all functional alleles. Fluorescent-labeled PCR products were then run on an ABI PRISM 310 Genetic-Analyzer. The data was analyzed by GeneMapper software version 3.1. Clonotype analysis suggested that activated T cells are present in breast cancer. More TRBV usage were detected among CD4+ helper and regulatory subsets, with Gaussian-like pattern in the majority of functional TRBV families; whereas CD8+ cytotoxic T cells showed oligoclonality in almost all TRBV families with one or two dominant peaks in each family. Similar pattern in some of these TRBVs were also observed among controls. Having no expression or polyclonality in the controls, the oligoclonal pattern observed in the TRBV18, however, appears to be specific to breast cancer patients. This phenomenon may reflect the existence of new antigenic stimulation(s) in BC patients, preferentially activating those clones of T cells that express TRBV18. Show more

Keywords: Breast cancer, TCR clonotype, Tregs, cytotoxic T cells, helper T cells

DOI: 10.3233/CBM-181295

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 733-745, 2018

Authors: Velmurugan, Bharath Kumar | Chang, Wei-Hsiang | Chung, Chia-Min | Yeh, Chung-Min | Lee, Chien-Hsun | Yeh, Kun-Tu | Lin, Shu-Hui

Article Type: Research Article

Abstract: BACKGROUND: Discoidin domain receptors (DDRs), a collagen receptor tyrosine kinase, play a major role in cancer progression. DDR2 has been suggested as a prognostic marker in several cancer types; however, the correlation between DDR2 expression and clinical outcome of oral cancer patients in Taiwan population has not been investigated. MATERIALS AND METHODS: In the present study we sought to determine the clinical significance of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2) expression in oral squamous cell carcinoma (OSCC) patients. We examined DDR2 expression in OSCC specimens by immunohistochemistry and then we analyzed the association of DDR2 …expression with clinicopathological factors in OSCC. RESULTS: We divided 254 OSCC cases into two groups based on DDR2 expression levels and compared with several clinicopathological factors and their overall survival. The group with high DDR2 expression had significantly higher frequencies of lymph node metastasis (P = 0.0094) and AJCC stage (P = 0.0058) compared to the group with low DDR2 expression. Furthermore, the lymph node metastasis oral cancer patients with high DDR2 expression had low survival rate than low DDR2 group (P = 0.0458). CONCLUSIONS: Our data indicate that DDR2 is a potent biomarker that can be used as an effective therapeutic target for treating OSCC patients with lymph node metastasis. Show more

Keywords: DDR2, lymph node metastasis, IHC, OSCC, biomarker

DOI: 10.3233/CBM-181302

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 747-753, 2018

Authors: Yoshida, Tetsuya | Kageyama, Susumu | Isono, Takahiro | Yuasa, Takeshi | Kushima, Ryoji | Kawauchi, Akihiro | Chano, Tokuhiro

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Renal cell carcinoma (RCC) is the urological malignancy with the highest mortality rate and is increasing in incidence. The prognostic and predictive biomarkers are highly desired. This study aims to investigate the significance of superoxide dismutase 2 (SOD2) as a clinical biomarker in patients with renal cell carcinomas. METHODS: A cohort of 97 patients with RCC was analyzed retrospectively using various clinical parameters and SOD2 expression by immunohistochemistry. RESULTS: Cases with stronger SOD2 positivity of the tumor in comparison to the adjacent normal renal tubule by immunohistochemistry were categorized as high SOD2 …and were associated with worse overall survivals (p = 0.005). In particular, in cases with metastatic RCC, high SOD2 expression in the tumors was significantly associated with a worse overall survival (p = 0.001), and the maximum critical risk. Treatment with current molecular targeting therapies did not improve the prognoses of cases with metastatic or recurrent RCC. CONCLUSIONS: High SOD2 expression can be predictive of a poor clinical outcome and be clinically useful in the follow-up of metastatic RCC. Therapeutics for metastatic RCCs require further improvement, such as supplementary administration of agents targeting mitochondrial SOD2. Show more

Keywords: Metastasis, molecular targeting therapy, renal cell carcinoma, superoxide dismutase 2

DOI: 10.3233/CBM-181308

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 755-761, 2018

Authors: Li, Xiao | Hu, Wei-Wei | Wang, Li | Yang, Xiang-Hui

Article Type: Research Article

Abstract: BACKGROUND: Oral squamous cell carcinoma is a malignant tumor which is particularly common in the developing world, mostly in older males. OBJECTIVE: Although gene expression analyses had been performed previously, to our best knowledge, systemic co-expression analysis for this disease is still lacking to date. METHODS: In this study, we built the co-expression modules with the help of Weighted Correlation Network Analysis (WGCNA) and investigated the function enrichment of co-expression genes from important modules by bioinformatics analysis. RESULTS: A total of 10 co-expression modules were conducted for 4500 genes from 167 oral squamous …cell carcinoma samples. Number of genes for each module ranged from 52 to 1112, with the mean of 450. Interaction relationships of hub-genes between pairwise modules showed great differences, suggesting the high confidence of modules. Functional enrichments of the co-expression modules exhibited great differences. Furthermore, genes in the module ME blue and module ME magenta significantly enriched in hsa05332 (Graft-versus-host disease) and hsa05330 (Allograft rejection), and the two pathways were associated with the oral squamous cell carcinoma. CONCLUSION: Together, our findings provided the framework of co-expression gene modules of oral squamous cell carcinoma and further understanding of these modules at functional aspect. Show more

Keywords: Oral squamous cell carcinoma, WGCNA, co-expression modules, function enrichment

DOI: 10.3233/CBM-181314

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 763-771, 2018

Authors: Feng, Runhua | Lu, Sheng | Sah, Birendra K. | Beeharry, Maneesh K. | Zhang, Huan | Yan, Min | Liu, Bingya | Li, Chen | Zhu, Zhenggang

Article Type: Research Article

Abstract: BACKGROUND: Predicting lymph node metastasis (LNM) accurately is vital to design optimal treatment strategies preoperatively for gastric cancer (GC) patients. However, conventional tumor biomarkers and imaging techniques are not sufficient to predict LNM before surgery. miR-126 has been reported to play important roles in tumor metastasis which may represent a novel tumor biomarker. OBJECTIVE: To assess the utility of the combination of serum miR-126 and multi-detector computed tomography (MDCT) in predicting LNM preoperatively in GC. METHODS: Quantitative real-time polymerase chain reaction was performed to examine the serum miR-126 expression levels in 338 GC patients. MDCT was …also performed. The cut-off value of preoperative serum miR-126 level for LNM was determined by receiver characteristic curve (ROC) analysis. Logistic regression analysis was used to determine independent predictors for LNM. RESULTS: The serum miR-126 levels of GC patients with LNM were significantly lower compared with those without LNM (p < 0.05). In addition, the later the N stage was, the lower the serum miR-126 level was in GC patients (p < 0.05). With a cut-off value of 63.4, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of serum miR-126 for predicating LNM were 83.2%, 79.0%, 81.9%, 90.4% and 66.4%, respectively. The combination of serum miR-126 level and MDCT increased the accuracy of MDCT prediction for LNM from 69.2% to 86.7%. Serum miR-126 was an independent predictor for LNM. CONCLUSIONS: These results indicate for the first time that the combination of serum miR-126 and MDCT is useful for the prediction of LNM in GC. Show more

Keywords: Gastric cancer, miR-126, serum, computed tomography, lymph node metastasis

DOI: 10.3233/CBM-181324

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 773-780, 2018

Authors: Tian, Yu | Feng, Yun

Article Type: Research Article

Abstract: BACKGROUND: Long noncoding RNA ultraconserved element 338 (uc.338) is a long non-coding RNA reported to function as a promoter in non-small cell lung cancer (NSCLC). However, the function and potential mechanism of uc.338 in NSCLC is still unclear. OBJECTIVE: The aim of the present study was to assess the effect of uc.338 on the prognosis of patients with NSCLC. METHODS: The expression levels of uc.338 in NSCLC tissues and matched normal lung tissues were examined by real-time quantitative PCR. Then the association between uc.338 levels with clinical variables as well as survival time was …investigated. RESULTS: We found that uc.338 expression levels were significantly upregulated in NSCLC compared with the matched noncancerous lung tissues (P < 0.01). In addition, increased uc.338 expression was significantly associated with TNM stage (P < 0.003), lymph node metastasis (P < 0.006) and distant metastasis (P < 0.002). More importantly, Kaplan-Meier survival analysis demonstrated that higher uc.338 expression levels were associated with a shorter overall survival (P < 0.0016) and disease-free survival (p < 0.0001) in NSCLC patients. Finally, univariate and multivariate Cox regression analyses revealed that uc.338 was an independent risk factor for overall survival and disease-free survival. CONCLUSIONS: Our results show that uc.338 may play an important role in tumorigenesis and progression and could serve as a potential independent prognostic biomarker for patients with NSCLC. Show more

Keywords: Long noncoding RNA, ultraconserved element 338, prognosis

DOI: 10.3233/CBM-181331

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 781-785, 2018

Authors: Zhong, Hua | Yang, Jun | Zhang, Bin | Wang, Xiaofang | Pei, Lihong | Zhang, Lei | Lin, Zhiqiang | Wang, Yanan | Wang, Chengbin

Article Type: Research Article

Abstract: Breast cancer is the most common malignancy in women which increases gradually all over the world. LncRNA GACAT3 has been found to be increased in gastric cancer and associated with tumor malignancy. However, whether GACAT3 plays a role in the regulation of breast cancer is not known. In the present study, we found that GACAT3 expression was increased in breast cancer tissues and cells compared with adjacent normal tissues and normal cells. High GACAT3 expression was correlated with the poor prognosis of breast cancer patients. GACAT3 and cyclin D2 (CCND2) contained a binding site of miR-497. miR-497 was decreased in …breast cancer tissues and cells compared with adjacent normal tissues and normal cells. Low miR-497 expression was correlated with the poor prognosis of breast cancer patients. In breast cancer tissues, the expression of miR-497 was negatively correlated with GACAT3. Downregulation of GACAT3 increased miR-497 expression. miR-497 mimic reduced the luciferase of GACAT3 and CCND2. Anti-miR-497 reversed the effects of GACAT3 downregulation. We also found that GACAT3 may act as a ceRNA for miR-497, enhancing the expression of CCND2. In conclusion, GACAT3 promotes breast cancer malignancy by sponging miR-497, leading to the enhancement of its endogenous target CCND2. These results suggest that GACAT3/miR-497/CCND2 is a potential therapeutic target and biomarker for breast cancer. Show more

Keywords: Breast cancer, CCND2, lncRNA GACAT3, malignancy, miR-497

DOI: 10.3233/CBM-181354

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 787-797, 2018

Authors: Huang, Yiqun | Zou, Yong | Lin, Luhui | Ma, Xudong | Chen, Hongpu

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-34a (miR-34a), as a tumor-suppressive miRNA, has been found to induce cell apoptosis in acute myeloid leukemia (AML). However, the diagnostic and prognostic significance of miR-34a in AML remains largely unknown. OBJECTIVE: We aimed to explore its associations with clinical characteristics and prognosis of AML patients. METHODS: This study detected serum miR-34a level in 117 diagnosed AML patients and 60 control subjects by using qRT-PCR, and results were compared to clinical features and patient outcome. Since cytogenetically-normal AML (CN-AML) has a good uniformity of cytogenetics and provides a perfect platform for detection of AML biomarkers, we …further analyzed miR-34a expression in 56 CN-AML subjects. RESULTS: We found that miR-34a was significantly downregulated in AML and CN-AML patients. MiR-34a underexpression was commonly observed in AML patients with intermediate/poor risk cytogenetic, and M5 subtype. ROC analysis demonstrated that serum miR-34a could well identify AML/CN-AML patients from healthy individuals. More importantly, miR-34a expression was found negatively correlated with aggressive clinical variable, and served as an independent prognostic indicator. In addition, AML/CN-AML patients with low miR-34a expression displayed shorter overall and recurrence free survival. CONCLUSIONS: Altogether, miR-34a might have an application as a diagnostic and prognostic indicator for AML patients. Show more

Keywords: miR-34a, biomarker, acute myeloid leukemia, diagnosis, prognosis

DOI: 10.3233/CBM-181381

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 799-805, 2018

Authors: Jia, Tao | Zhang, Run | Zhu, Hua-Yuan | Liang, Jin-Hua | Wang, Li | Wu, Wei | Cao, Lei | Li, Jian-Yong | Xu, Wei

Article Type: Research Article

Abstract: BACKGROUND: Peripheral blood absolute monocyte count (AMC) and lymphocyte to monocyte ratio (LMR) have strong prognostic value in various forms of lymphomas. It was found that higher AMC and lower LMR were associated with poor prognosis in B cell lymphoma. However, their prognostic significance in systemic anaplastic large cell lymphoma (sALCL) remained to be determined. OBJECTIVE: This study was aimed at investigating the prognostic significance of AMC and LMR in sALCL. METHODS: A total of 29 newly diagnosed patients with sALCL were retrospectively included in study, prognostic significance of AMC, LMR, performance status …(PS), international prognostic index (IPI), prognostic index for T-cell lymphomas (PIT) and other indicators were analyzed. RESULTS: Univariate analysis showed high AMC, LMR < 2.5, PS ⩾ 2, extranodal involvement, no response to treatment and B symptoms predicted inferior PFS; LMR < 2.5, no response to treatment, elevated LDH, IPI ⩾ 3, PIT ⩾ 2 and PS ⩾ 2 predicted inferior OS. High AMC, PS ⩾ 2 were independent prognostic factors for PFS; PS ⩾ 2, no response to treatment and elevated LDH were independent prognostic factors for OS. CONCLUSIONS: AMC was an independent prognostic factor for PFS in sALCL, and LMR < 2.5 also indicated poor prognosis. Show more

Keywords: Anaplastic large cell lymphoma, absolute monocyte count, absolute lymphocyte count, lymphocyte to monocyte ratio, prognosis

DOI: 10.3233/CBM-181505

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 807-813, 2018