Cancer Biomarkers - Volume 21, issue 2

Authors: Xu, Xiaohui | Cao, Lei | Zhang, Ye | Lian, Hongjian | Sun, Zhiwei | Cui, Yushang

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Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''.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/CBM229007.

Keywords: microRNA-1246, lung cancer, cell invasion, epithelial mesenchymal transition, CXCR4

DOI: 10.3233/CBM-170317

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 251-260, 2018

Authors: He, H.W. | Wang, N.N. | Yi, X.M. | Tang, C.P. | Wang, D.

Article Type: Research Article

Abstract: BACKGROUND: colorectal cancer (CRC) is the second leading cause of cancer and cancer-related death in the world. Noninvasive biomarkers for early diagnosis of CRC are highly demanded. OBJECTIVE: The up-regulation of specific microRNAs (miRNAs) in serum has been considered a promising biomarker of CRC and miR-24-2 may be a potential biomarker in the diagnosis the progression of CRC. METHODS: Sixty-eighty healthy subjects and 228 CRC patients were divided into six groups: control group, CRC 0, CRC I, CRC II, CRC III, CRC IV and CRC V. Serum level of miR-24-2 was measured by …real-time qPCR. Serum lipid profiles and oxidative-related molecules were also measured. RESULTS: Serum levels of miR-24-2 in CRC patients were significantly higher than healthy subjects (p < 0.05). In addition, the expression level of the miR-24-2 was decreased with the progression of CRC and reached the lowest level in CRC V. Spearman Rank Correlation analysis showed that miR-24-2 level was negatively related to the levels of superoxide dismutase (SOD) and reduced glutathione (GSH), aspartate transaminase (AST), alanine transaminase (ALT), cholesterol and triglyceride (p < 0.05). CONCLUSIONS: Serum miR-24-2 is a potential negative biomarker in the diagnosis of the progression of CRC patients and associated with biochemical indices. Show more

Keywords: miR-24-2, colorectal cancer, diagnostic biomarker, qRT-PCR

DOI: 10.3233/CBM-170321

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 261-267, 2018

Authors: Hong, Ze | Zhang, Rongrong | Qi, Haixiao

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-195 acts as a tumor suppressor in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) remains largely undefined. OBJECTIVE: To investigate the diagnostic and prognostic relevance of miR-195 in this malignancy. METHODS: Expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and normal controls were detected by real-time quantitative PCR. Then, receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression analysis were performed to evaluate the diagnostic and prognostic relevance of serum miR-195 in pediatric AML. …RESULTS: Compared to normal controls, the expression levels of miR-195 in both bone marrow and patients’ sera were significantly decreased (both P < 0.001). In addition, serum miR-195 had an optimal diagnostic cut-off point (2.09) for pediatric AML with sensitivity of 68.87% and specificity of 96.23%. The area under the ROC curve (AUC) based on serum miR-195 was 0.910. Moreover, patients with low serum miR-195 level more often had French-American-British classification subtype M7 (P = 0.02), unfavorable karyotypes (P = 0.01), and shorter relapse-free and overall survivals (both P = 0.001) than those with high serum miR-195 level. Furthermore, the multivariate analysis identified serum miR-195 level as an independent prognostic factor for both relapse-free and overall survivals. CONCLUSION: The findings of this study suggest that the aberrant expression of miR-195 may play crucial roles in the development and progression of pediatric AML patients. Serum miR-195 may serve as a promising marker for monitoring the occurrence of this disease and predicting the clinical outcome of patients. Show more

Keywords: Pediatric acute myeloid leukemia, microRNA-195, serum, real-time quantitative PCR, prognosis

DOI: 10.3233/CBM-170327

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 269-275, 2018

Authors: Liao, Xinhui | Chen, Jieqing | Liu, Yuchen | He, Anbang | Wu, Jianting | Cheng, Jianli | Zhang, Xintao | Lv, Zhaojie | Wang, Feng | Mei, Hongbing

Article Type: Research Article

Abstract: OBJECTIVES: To study the expression pattern of long non-coding RNA FGFR3 antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer. METHODS: The differential expression levels of FGFR3-AS1 and FGFR3 in tumor tissues and paired normal tissues were determined using Real-Time qPCR in a total of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson’s coefficient correlation was used for expression correlation assay. Expression differences of FGFR3-AS1 were analyzed according to grading and staging. FGFR3 protein was detected by western blot assay. Human bladder cancer T24 and …5637 cell lines were transiently transfected with FGFR3-AS1-specific siRNA or negative control siRNA. The cell proliferation changes of transfected bladder cancer cells were determined using CCK-8 assay. Apoptosis caused by knockdown of FGFR3-AS1 was evaluated using ELISA assay. Motility changes induced by knockdown of FGFR3-AS1 were measured using wound healing assay and transwell assay. RESULTS: Both FGFR3-AS1 and FGFR3 were overexpressed in bladder cancer tissues compared to matched normal tissues. They were also positively expressed in bladder cancer. FGFR3-AS1 expression levels were higher in high grade tumors than those in low grade tumors. FGFR3-AS1 expression levels were higher in invasive tumors than those in non-invasive tumors. Cell proliferation inhibition, increased apoptosis, and decreased motility were observed in FGFR3-AS1 siRNA-transfected T24 and 5637 cell lines. CONCLUSIONS: FGFR3-AS1 plays an oncogenic role in human bladder cancer. Knockdown of FGFR3-AS1 may provide a potential new therapeutic approach to this disease. Show more

Keywords: lncRNA, FGFR3-AS1, bladder cancer

DOI: 10.3233/CBM-170354

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 277-285, 2018

Authors: Tan, Dan | Sheng, Li | Yi, Qing-Hua

Article Type: Research Article

Abstract: OBJECTIVE: To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. METHODS: A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. RESULTS: PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk …for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1 /PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. CONCLUSION: PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer. Show more

Keywords: Ovarian cancer, PD-1, PD-L1, polymorphism, clinicopathologic features, prognosis

DOI: 10.3233/CBM-170357

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 287-297, 2018

Authors: Sun, Handong | Tang, Weiwei | Rong, Dawei | Jin, Hui | Fu, Kai | Zhang, Wenling | Liu, Zhaojing | Cao, Hongyong | Cao, Xiufeng

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNAs) have been found playing important roles in regulating cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we are aimed to investigate the relationship between a new circular RNA named hsa_circ_0000520 and gastric cancer development. METHODS: The hsa_circ_0000520 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue, cell and plasma levels, respectively. Then, the association between the expression level of hsa_circ_0000520 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of …hsa_circ_0000520-miRNA-mRNA interactions was predicated. RESULTS: In this study, hsa_circ_0000520 was first found to be significantly down-regulated in gastric cancer tissues, plasma and gastric cancer cell lines compared with control cases. Clinicopathological features showed that hsa_circ_0000520 level in GC tissues was negatively associated with TNM stage and in GC plasma linked with CEA expression. Finally, a total of 9 miRNAs and 9 candidate mRNA were predicted to have an interaction with hsa_circ_0000520. CONCLUSIONS: We first identified that hsa_circ_0000520 was significantly down-regulated in gastric cancer. Our study indicated hsa_circ_0000520 might serve as a novel biomarker for gastric cancer and is involved in gastric carcinoma development. Show more

Keywords: Gastric cancer, hsa_circ_00000520, diagnosis, miRNA, mRNA

DOI: 10.3233/CBM-170379

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 299-306, 2018

Authors: Ji, Juanli | Zhen, Weiguo | Si, Yuan | Ma, Wenjing | Zheng, Lanlan | Li, Chen | Zhang, Yonghong | Qin, Shanshan | Zhang, Te | Liu, Pengfei | Zheng, Xin | Liu, Ying

Article Type: Research Article

Abstract: BACKGROUND: The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which involves in the progression of several human malignancies. Development of cisplatin (DDP) resistance is the obstacle to an effective control of gastric cancer (GC) clinically. OBJECTIVE: We thus assessed whether CIP2A expression is associated with sensitivity of GC to DDP. METHODS: Real-time quantitative PCR, immunohistochemical analysis, or western blotting was performed to detect CIP2A expression in GC patients’ tissues. SGC7901/DDP cells were transfected with CIP2A siRNA. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used …to measure cell apoptosis. RESULTS: CIP2A has higher expression in DDP-resistant GC patients. DDP-resistant GC patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. CIP2A knockdown in DDP-resistant GC cells resulted in attenuated proliferative abilities and increased apoptosis level. CIP2A depletion sensitizes DDP-resistant cells to DDP and CIP2A overexpression antagonizes DDP-sensitive cells to DDP. CIP2A influences the expression of multidrug resistance-related proteins in GC cells. CONCLUSIONS: Our results suggested that CIP2A oncoprotein plays an important role in DDP resistance of GC and could serve as a novel therapeutic target for the treatment of GC patients with DDP resistance. Show more

Keywords: CIP2A, gastric cancer, DDP, chemoresistance, apoptosis

DOI: 10.3233/CBM-170416

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 307-316, 2018

Authors: Fu, Shuang | Niu, Ye | Zhang, Xin | Zhang, Ji-Rong | Liu, Zhi-Ping | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Squamous cell cervical carcinoma is the most common gynecological malignant disorder worldwide. Early detection of squamous cell cervical carcinoma is needed for proper clinical management. Squamous cell carcinoma antigen (SCCA) is commonly used as a tumor marker for squamous cell cervical carcinoma. Platelet distribution width (PDW) is an indicator of platelet activation. Prealbumin is a negative acute-phase protein. OBJECTIVE: The aim of this study was to investigate the ability of SCCA, PDW, and prealbumin individually or in combination, to distinguish between cervical carcinoma and control subjects. MEHTODS: Two hundred and twenty patients …with squamous cell cervical carcinoma and 211 control subjects were included in the study. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. RESULTS: Our results showed that SCCA and PDW were higher, and prealbumin was lower in cervical carcinoma patients than in control subjects. Single biomarker had AUC value ranging from 0.753 for SCCA to 0.845 for PDW. The combination of SCCA and PDW increased the AUC to 0.900 (p < 0.0001). In addition, the combination of SCCA, PDW and prealbumin exhibited a significantly larger AUC of 0.917 (0.887–0.942), significantly higher than those of any single marker. CONCLUSIONS: The combined use of SCCA, PDW and prealbumin can accurately distinguish squamous cell cervical carcinoma from control subjects. This promising approach could be helpful in early detection of squamous cell cervical carcinoma. Show more

Keywords: Cervical carcinoma, platelet distribution width, prealbumin, squamous cell carcinoma antigen

DOI: 10.3233/CBM-170442

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 317-321, 2018

Authors: Masetti, Michele | Acquaviva, Giorgia | Visani, Michela | Tallini, Giovanni | Fornelli, Adele | Ragazzi, Moira | Vasuri, Francesco | Grifoni, Daniela | Di Giacomo, Simone | Fiorino, Sirio | Lombardi, Raffaele | Tuminati, David | Ravaioli, Matteo | Fabbri, Carlo | Bacchi-Reggiani, Maria Letizia | Pession, Annalisa | Jovine, Elio | de Biase, Dario

Article Type: Research Article

Abstract: BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS , TP53 , SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery (“LS”) were analyzed for KRAS , TP53 , IDH1 , NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 …was tested using immunohistochemistry. MGMT promoter methylation was investigated. RESULTS: Tumors from “LS” have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. CONCLUSIONS: Our data indicate that absence of KRAS , TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome. Show more

Keywords: Pancreatic adenocarcinoma, KRAS, TP53, SMAD4, mutation

DOI: 10.3233/CBM-170464

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 323-334, 2018

Authors: Feng, Runhua | Sah, Birendra K. | Beeharry, Maneesh K. | Yuan, Fei | Su, Liping | Jin, Xiaolong | Yan, Min | Liu, Bingya | Li, Chen | Zhu, Zhenggang

Article Type: Research Article

Abstract: BACKGROUND: miR-126 functions as a tumor suppressor in gastric cancer (GC) by negatively regulating Crk protein expression post-transcriptionally. OBJECTIVE: The aim of this study was to investigate the associations of miR-126 and Crk protein expression levels, alone or in combination, with the clinicopathological characteristics and prognosis of GC patients. METHODS: The expression levels of miR-126 and Crk protein in 338 GC patients were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. The relationship of miR-126 and Crk protein expression with clinicopathologic characteristics and clinical outcome was evaluated. RESULTS: …Compared with matched adjacent non-tumor tissues, miR-126 was significantly down-regulated while Crk protein was significantly up-regulated in tumor tissues. A reduced miR-126 expression and an elevated Crk protein expression, alone or in combination, statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Multivariate analysis showed that combined miR-126-low/Crk protein-high expression was an independent unfavorable prognostic factor of GC. CONCLUSIONS: These results indicate for the first time that miR-126 down-regulation and Crk protein up-regulation may be synergistically associated with tumor progression in GC and may predict unfavorable prognosis of GC. Show more

Keywords: Gastric cancer, microRNA, miR-126, Crk, prognosis

DOI: 10.3233/CBM-170472

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 335-343, 2018

Authors: Benlahfid, Mohammed | Traboulsi, Wael | Sergent, Frederic | Benharouga, Mohamed | Elhattabi, Khalid | Erguibi, Driss | Karkouri, Mehdi | Elattar, Hicham | Fadil, Abdelaziz | Fahmi, Yassine | Aboussaouira, Touria | Alfaidy, Nadia

Article Type: Research Article

Abstract: BACKGROUND: The highest risk factor for mortality among malignant tumors is metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor which biological activity is mediated via two G protein-coupled receptors, prokineticin receptor1 (PROKR1) and PROKR2. Recent studies suggested that EG-VEGF expression is deregulated in multiple cancers including colorectal cancer (CRC). METHODS: Using distinctive CRC and peritoneal carcinomatosis (PC) cohorts and a corresponding control cohort, we determined the circulating levels of EG-VEGF and its in situ expression, and that of its related receptors. RESULTS: Circulating EG-VEGF levels were significantly increased …in patients with metastatic PC compared to CRC and control patients (p < 0.05). Furthermore, according to clinicopathologic examinations, local EG-VEGF expression correlated with higher tumor and nodal stages (p < 0.001) of CRC. EG-VEGF and PROKR2 were highly expressed in colorectal primary lesions compared to positive controls. PROKR1 expression was lower and did not change in tumor specimens. Also, EG-VEGF and its receptor PROKR2 were differentially expressed in the colorectal primary lesions and in the control groups. CONCLUSION: Altogether these findings suggest that EG-VEGF/receptors system might be an important actor in the CRC progression into PC and might be involved in the ability of tumor cells to invade other organs. Circulating EG-VEGF could be proposed as a prognostic marker in human CRC and its progression into PC. Show more

Keywords: Prokineticin, colorectal cancer, peritoneal carcinomatosis, EG-VEGF

DOI: 10.3233/CBM-170499

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 345-354, 2018

Authors: Wu, Dong-Ming | Shi, Jiao | Liu, Teng | Deng, Shi-Hua | Han, Rong | Xu, Ying

Article Type: Research Article

Abstract: Cervical cancer is the fourth most common malignancy among women worldwide, and continued research to discover biomarkers or therapeutic targets will aid early diagnosis and treatment of this cancer. Here, we investigated novel cervical cancer biomarkers using integrated analysis of high-throughput sequencing data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We have identified nine genes of interest that appear to be involved in cervical cancer development: SPARCL1 , SYCP2 , KIF4A , PRC1 , TOP2A , LAMP3 , KIF20A , MCM2 , and APOBEC3B . Furthermore, gene ontology (GO) and co-expression analysis of these …differentially expressed genes indicated that SPARCL1 may play a core role in cervical cancer development. Further, we analyzed the expression of these nine genes during the progression of cervical cancer, and found that SPARCL1 is also related to precancerous lesions and migration processes during cervical cancer pathogenesis. Finally, we validated these observations by investigating SPARCL1 expression in cervical cancer tissue and serum samples. The diagnostic specificity of serum SPARCL1 in cervical cancer occurrence was also compared with other high incidence diseases. All of these data indicate that SPARCL1 may be a novel cancer predictive marker and a potential therapeutic target for tumor development and progression in cervical cancer. Show more

Keywords: Cervical cancer, SPARCL1, marker

DOI: 10.3233/CBM-170501

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 355-365, 2018

Authors: Wang, Dong | Ji, Zhi-Gang | Li, Han-Zhong | Zhang, Yu-Shi

Article Type: Research Article

Abstract: OBJECTIVE: To assess whether adrenalectomy may improve biochemical and metabolic impairment for patients with subclinical Cushing syndrome (SCS) due to adrenal incidentaloma (AI) compared with conservative management. METHODS: A total of 87 patients with SCS due to AI in Peking Union Medical College Hospital between September 2011 and January 2016 have been treated. Forty-eight patients underwent laparoscopic adrenalectomy (operative group), whereas 39 were managed conservatively (control group). RESULTS: The duration of follow-up was 32.5 ± 10.6 months in operative group, and 30.1 ± 13.1 months in control group, respectively. In …the operative group, laboratory corticosteroid parameters normalized in all patients but not in the control group. In the operative group, BP of hypertensive patients improved or normalized (22 of 48); to the contrary, in the control group, cure or improvement was never achieved among the patients with hypertension, whereas a worsening was observed in 5 patients (P = 0.004). No significant difference was found in glycemic control and blood lipid change between the two groups. However, a decrease in triglyceridaemia and HBA1c was found in operative group compared with the control group (P = 0.011 and P = 0.017, respectively). Substitutive corticosteroid treatment was administered in 3 patients due to postoperative adrenal insufficiency during hospital stay, and the duration of treatment was 9 weeks, 10 weeks and 12 weeks, respectively. CONCLUSIONS: Laparoscopic adrenalectomy should be performed for patients with SCS due to AI. Show more

Keywords: Subclinical Cushing’s syndrome, adrenal incidentaloma, adrenalectomy

DOI: 10.3233/CBM-170531

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 367-372, 2018

Authors: Fang, Enhao | Zhang, Xiuqing

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is the second most common cause of death from cancer in women in the United States. As the molecular mechanism of BC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing molecular mechanism of breast cancer initiation and progression. OBJECTIVE: This study aimed to identify potential biomarkers and survival analysis of hub genes for BC treatment. METHODS: The differentially expressed genes (DEGs) between breast cancer and normal cells were screened using microarray data obtained from the Gene Expression Omnibus (GEO) database. …Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS) analysis of hub genes was performed by the Kaplan-Meier plotter online tool. Finally, the potential molecular agents were identified with Connectivity Map (cMap) database. RESULTS: A total of 585 DEGs were obtained, which were significantly enriched in the terms related to positive regulation of cell migration, regulation of cell proliferation and focal adhesion. KEGG pathway analysis showed that the significant pathways included Focal adhesion, Pathways in cancer, ECM-receptor interaction, Ribosome, Transcriptional misregulation in cancer and other signaling pathways about cancer. The PPI network was established with 576 nodes and 1943 edges. A significant module was found from the PPI network, the enriched functions and pathways included ECM-receptor interaction and Focal adhesion. CONCLUSIONS: Fifteen genes were selected as hub genes because of high degrees, among which, low expression of four genes was associated with worse OS of patients with BC, including RPS9 , RPL11 , RPS14 and RPL10A . Additionally, the small molecular agent emetine may be a potential drug for BC. Show more

Keywords: Breast cancer, bioinformatics analysis, differently expressed genes, hub genes, therapeutic agent, survival analysis

DOI: 10.3233/CBM-170550

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 373-381, 2018

Authors: Zuo, Jiangcheng | Yu, Yalan | Zhu, Man | Jing, Wei | Yu, Mingxia | Chai, Hongyan | Liang, Chunzi | Tu, Jiancheng

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS: The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore …whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS: In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS: Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer. Show more

Keywords: miR-155, breast cancer, cancer stem cell, MDA-MB-231, Doxorubicinol

DOI: 10.3233/CBM-170642

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 383-392, 2018

Authors: Hussain, Lal | Ahmed, Adeel | Saeed, Sharjil | Rathore, Saima | Awan, Imtiaz Ahmed | Shah, Saeed Arif | Majid, Abdul | Idris, Adnan | Awan, Anees Ahmed

Article Type: Research Article

Abstract: Prostate is a second leading causes of cancer deaths among men. Early detection of cancer can effectively reduce the rate of mortality caused by Prostate cancer. Due to high and multiresolution of MRIs from prostate cancer require a proper diagnostic systems and tools. In the past researchers developed Computer aided diagnosis (CAD) systems that help the radiologist to detect the abnormalities. In this research paper, we have employed novel Machine learning techniques such as Bayesian approach, Support vector machine (SVM) kernels: polynomial, radial base function (RBF) and Gaussian and Decision Tree for detecting prostate cancer. Moreover, different features extracting strategies …are proposed to improve the detection performance. The features extracting strategies are based on texture, morphological, scale invariant feature transform (SIFT), and elliptic Fourier descriptors (EFDs) features. The performance was evaluated based on single as well as combination of features using Machine Learning Classification techniques. The Cross validation (Jack-knife k-fold) was performed and performance was evaluated in term of receiver operating curve (ROC) and specificity, sensitivity, Positive predictive value (PPV), negative predictive value (NPV), false positive rate (FPR). Based on single features extracting strategies, SVM Gaussian Kernel gives the highest accuracy of 98.34% with AUC of 0.999. While, using combination of features extracting strategies, SVM Gaussian kernel with texture + morphological, and EFDs + morphological features give the highest accuracy of 99.71% and AUC of 1.00. Show more

Keywords: Prostate cancer, support vector machine (SVM), decision tree, Bayesian approach, morphological, scale invariant feature transform (SIFT), texture, and elliptic fourier descriptors (EFDs)

DOI: 10.3233/CBM-170643

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 393-413, 2018

Authors: Ruan, Libo | Chen, Jun | Ruan, Litao | Yang, Tianrui | Wang, Ping

Article Type: Research Article

Abstract: MicroRNAs are a class of small non-coding RNA molecules that play crucial roles in the initiation and progression of lung cancer. This study was undertaken to investigate the expression and roles of miR-186 in lung cancer. Ectopic expression experiments demonstrated that miR-186 functions as a tumor suppressor. Bioinformatic predictions, a luciferase reporter assay, and protein expression analysis suggested that miR-186 could inhibit the protein levels of SIRT6, a purported tumor suppressor gene. Collectively, our results indicated that miR-186 could inhibit lung cancer progression through targeting SIRT6 and that miR-186 may be a therapeutic target for lung cancer.

Keywords: Lung cancer, microRNA, miR-186, SIRT6, apoptosis

DOI: 10.3233/CBM-170650

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 415-423, 2018

Authors: Zuo, Li | Ying, Jiang-Shan | Zhang, Feng-Chun | Xu, Ying-Chun

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the correlation of katanin P60 expression with clinicopathological grade and overall survival (OS) in patients with breast cancer (BC). METHODS: Three hundred and four operative BC patients were retrospectively reviewed in this cohort study. Tumor tissue sample was acquired from each patient during surgery. Immunofluorescent staining was used to assess katanin P60 expression. RESULTS: There were 265 BC patients with katanin P60 negative expression and 75 patients with katanin P60 positive expression. Higher N stage (p < 0.001) and TNM stage (p < …0.001) were observed in katanin P60 positive expression group compared to katanin P60 negative expression group. Kaplan-Meier (K-M) curves showed association of katanin P60 positive expression status with shorter OS. Multivariate Cox analysis illustrated katanin P60 positive expression (p < 0.001) could independently predict worse OS. Subgroups analysis indicated that katanin P60 positive expression correlated with worse OS in patients of TNM stage II (p = 0.001) and stage III (p =0.001), while no correlation was found between katanin P60 expression and OS in BC patients with stage I (p = 0.538). According to molecular subtypes, katanin P60 positive expression was correlated with shorter OS in patients with HER2 + HR + (p < 0.001), HER2 + HR - (p < 0.001) and HER2 - HR - (p = 0.001) status compared to katanin P60 negative expression, while no correlation between katanin P60 expression and OS was observed in patients with HER2 - HR + (p = 0.073). CONCLUSION: Katanin P60 positive expression was correlated with higher lymph node metastasis and worse OS, and it could be regarded as a novel and convincing biomarker to independently predict the prognosis of BC patients. Show more

Keywords: Tumor tissue, katanin P60, breast cancer, prognosis

DOI: 10.3233/CBM-170666

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 425-432, 2018

Authors: Rodríguez-Molinero, Alejandro | Hercbergs, Aleck | Sarrias, Manuel | Yuste, Antonio

Article Type: Research Article

Abstract: Preclinical studies have attributed 3,3’,5-triiodo-L-thyronine (T3) a direct negative effect on tumor progression, as well as chemosensitizing, differentiating and immunomodulatory properties. On the other hand, L-thyroxine (T4), via a thyroid hormone receptor on plasma membrane integrin α vβ 3, promotes solid tumor growth and neoangiogenesis, therefore lowering endogenous T4 reduces tumor growth rate. We present the case of two patients with metastatic triple negative breast cancer and metastatic pancreatic cancer respectively, who benefit of the sole treatment with antithyroid drugs and exogenous administration of T3 (liothyronine). In these cases tumor growth was accompanied by T3 depletion …in plasma, which may represent a novel marker for progression. Show more

Keywords: Neoplasm metastasis, pancreatic neoplasms, thyroid hormones, triiodothyronine, triple negative breast neoplasms

DOI: 10.3233/CBM-170668

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 433-438, 2018

Authors: Wang, Yang-Kun | Wang, Su-Nan | Li, Ying-Ying | Wang, Gong-Ping | Yun, Tian | Zhu, Chao-Ya | Yang, Bin-Feng | Li, Cong-Yang | Jiang, Bo | Zhu, Mei-Ling

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma. RESULTS: The expression rate of HER2 protein was 39.3% (53/135). Among these positive cases, patients with HER2 protein (3+) accounted for 9.6% (13/135), patients with HER2 protein (2+) accounted for …13.3% (18/135), and patients with HER2 protein (1+) accounted for 16.3% (22/135). The amplification rate of the HER2 gene was 35.8% (19/53). In the detection of the mRNA expression of ERCC1, TUBB3 and TYMS, 45 patients had low and moderate single gene expression, 50 patients had low and moderate double gene expression, 22 patients had low and moderate mRNA expression for ERCC1, TUBB3 and TYMS, and 18 patients had no low and moderate expression. Among the 53 patients with HER2 protein expression and 22 patients with low and moderate mRNA expression of ERCC1, TUBB3 and TYMS, 12 patients received chemotherapy and trastuzumab. Follow-up results revealed that HER2 gene status was positively correlated with the therapeutic effect of the combined treatment in patients with low mRNA expression of ERCC1, TUBB3 and TYMS. Among these patients, five patients with extensive HER2 (3+), HER2 cluster-specific amplification, and low mRNA expression of ERCC1, TUBB3 and TYMS had a total survival of up to 19.1 months. CONCLUSIONS: The detection of HER2 in gastric cancer is highly heterogeneity, and the combined detection of HER2 protein expression, HER2 gene amplification and chemosensitivity can provide important reference markers for the benefit of antitumor drugs. Show more

Keywords: Stomach neoplasms, HER2 gene, HER2 protein, FISH, IHC, fluorescence RT-PCR

DOI: 10.3233/CBM-170671

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 439-447, 2018

Authors: Cong, Chunlei | Wang, Wenbo | Tian, Jun | Gao, Tianqi | Zheng, Weizhuo | Zhou, Changlin

Article Type: Research Article

Abstract: BACKGROUND: It has been demonstrated that microRNAs (miRNAs) play an important role in the carcinogenesis of osteosarcoma. OBJECTIVE: The aim of the present study was to determine the diagnostic and prognostic value of serum miR-124 in osteosarcoma. METHODS: The serum miR-124 expression levels in 114 osteosarcoma patients, 40 periostitis patients and 50 normal controls were detected using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of serum miR-124 was remarkably decreased in osteosarcoma patients when compared to periostitis patients and healthy controls (both p < …0.05). The serum miR-124 levels in osteosarcoma patients were significantly elevated after receiving surgical treatment (p < 0.01). Furthermore, the area under the receiver-operating characteristic (ROC) curve (AUC) for serum miR-124 was 0.846, combining with 79.8% sensitivity and 86.00% specificity. A significant correlation was detected between serum miR-124 expression and distant metastasis (p = 0.0256) as well as clinical stage (p = 0.0006). Similarly, serum miR-124 levels in patients with advanced clinical stage or positive distant metastasis were significantly decreased. Moreover, the Kaplan-Meier method with log-rank test showed that osteosarcoma patients with lower serum miR-124 levels had unfavorable 5 year overall survival and disease free survival rates. Finally, multivariate analysis revealed that serum miR-124 was an independent prognostic indicator for osteosarcoma. CONCLUSIONS: These findings suggested that serum miR-124 might be a promising biomarker with diagnostic and prognostic value for osteosarcoma. Show more

Keywords: Serum miR-124, osteosarcoma, prognosis, diagnosis

DOI: 10.3233/CBM-170672

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 449-454, 2018

Authors: Fan, Limei | Liu, Zongyu | Zhang, Yong | Zhu, He | Yu, Huimei | Yang, Fan | Yang, Ruiqi | Wu, Fei

Article Type: Research Article

Abstract: OBJECTIVE: Cervical squamous cell carcinoma seriously threats to patient’s life and health. MiRNAs have role of regulating cell growth, proliferation, and death. MiRNAs can promote or inhibit cell growth and proliferation. This study discussed the role of miRNA373 in regulating cervical squamous cell carcinoma growth, proliferation, and apoptosis. PATIENTS AND METHODS: MiRNA373 and scramble miRNA were synthetized and transfected to cervical squamous cell carcinoma SiHa cells by lipofectamine. IAPs plasmid and miRNA373 were sequentially transfected to SiHa cells. MTT assay, caspase-3 activity, and flow cytometry were applied to test miRNA373 and IAPs impacts on cell growth, …proliferation, and apoptosis. Western blot was adopted to determine IAPs expression. RESULTS: MiRNA373 transfection obviously reduced SiHa cell growth, induced phosphatidylserine eversion and caspase-3 activation, and declined IAPs expression. IAPs interference significantly enhanced miRNA373 induced SiHa cell apoptosis. IAPs overexpression markedly restrained miRNA373 induced SiHa cell apoptosis. CONCLUSIONS: MiRNA373 transfection suppressed SiHa cell growth and proliferation. MiRNA373 induced SiHa cell apoptosis possibly through downregulating IAPs, suggesting that IAPs might be a target for cervical squamous cell carcinoma treatment. Show more

Keywords: miRNA373, IAPs, SiHa cell, apoptosis

DOI: 10.3233/CBM-170692

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 455-460, 2018

Authors: Luo, Xianyuan | Hou, Nan | Chen, Xiaohua | Xu, Zhiping | Xu, Juqing | Wang, Lin | Yang, Shu | Liu, Suyao | Xu, Li | Chen, Yan | Xiong, Lin | Wang, Jun | Fan, Weifei | Xu, Jiaren

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines …and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p < 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p = 0.038), N (p = 0.020) and TNM stage (p = 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p = 0.002) and T (p = 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis. Show more

Keywords: NDRG3, NSCLC, prognosis

DOI: 10.3233/CBM-170711

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 461-469, 2018

Authors: Xu, Xin-Ran | Wang, Xin | Zhang, Hong | Liu, Ming-Yan | Chen, Qi

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the clinical significance of serum Smac, HE4 and CA125 alone or combined for detecting endometriosis-associated ovarian cancer (EAOC). METHODS: The level of serum Smac, HE4 and CA125 in 40 healthy controls, 40 cases of benign endometriosis ovarian tumor, and 60 cases of EAOC were detected by ELISA and electrochemical immune method. RESULTS: Serum Smac expression level was significantly lower in the EAOC group than in the control group and benign ovarian tumor group (P < 0.05), while HE4 and CA125 expression levels were significantly higher …in the EAOC group than the other two groups. The sensitivity of Smac single detection was up to 91.67%, and the specificity of HE4 was up to 98.75%. Furthermore, the sensitivity of Smac + HE4 + CA125 combined was the highest, which reached up to 98.33%; but the specificity was low, which reached up to 75%. The serum expression level differences before and after surgery were statistically significant. As the number of chemotherapies increases, the Smac level increased, and HE4 and CA125 levels gradually decreased. Furthermore, Smac increased to normal at the end of the 2 nd period of chemotherapy, while HE4 and CA125 decreased to normal in 2 nd and 3 rd period of chemotherapy, respectively. CONCLUSION: Serum Smac, HE4 and CA125 may play an important role in predicting EAOC and in monitoring the prognosis of postoperative EAOC. Show more

Keywords: Smac, HE4, CA125, endometriosis-associated ovarian cancer, chemotherapy

DOI: 10.3233/CBM-170720

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 471-477, 2018

Authors: Świtlik, Weronika | Karbownik, Michał Seweryn | Suwalski, Michał | Kozak, Józef | Szemraj, Janusz

Article Type: Research Article

Abstract: BACKGROUND: Although an immense effort has been made to develop novel diagnostic methods and treatment strategies for non-small cell lung cancer (NSCLC), the survival rate of this disease has remained virtually unchanged. Small non-coding RNAs called microRNAs (miRNAs) have appeared to be very promising biomarkers of cancer including NSCLC. OBJECTIVE: We investigated the expression level of six miRNAs, and subsequently we evaluated their diagnostic ability and their clinical significance. METHODS: We performed an analysis in 50 paired cancer and non-cancerous lung tissue samples collected from NSCLC patients. The RT-qPCR technique was used to …investigate the expression profile. RESULTS: Obtained results indicate that miR-30a-5p, miR-126-3p and miR-486-5p are downregulated, while miR-205-5p and miR-210-3p are upregulated in NSCLC tissue. Moreover, performed stepwise discriminant analysis determined the model including miR-30a-5p and miR-210-3p which tested on the test set (n = 30) revealed an AUC of 0.969 and provided 100% sensitivity and 80% specificity in discriminating NSCLC tissue from non-cancerous lung tissue. CONCLUSIONS: The present preliminary study demonstrated that five tested miRNAs were deregulated in cancer tissue. Moreover, miR-30a-5p together with miR-210-3p with excellent sensitivity and acceptable specificity may distinguish cancer tissue form non-cancerous tissue and thus may become a potential diagnostic biomarker for NSCLC. Show more

Keywords: Non-small cell lung cancer, microRNA, miR-30a-5p, miR-210-3p, biomarker, diagnosis

DOI: 10.3233/CBM-170767

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 479-488, 2018

Authors: Lin, Pingping | Pang, Qingsong | Wang, Ping | Lv, Xiying | Liu, Lanfang | Li, Aike

Article Type: Research Article

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

Keywords: MicroRNA-361, Gli1, Snail, EMT, esophageal cancer, invasion

DOI: 10.3233/CBM-170802

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 489-498, 2018