Cancer Biomarkers - Volume 26, issue 2

Authors: Zhu, Pengfeng | Tan, Qingqing | Jiang, Wen | Ou, Yangjun | Xu, Peizhen | Yuan, Lei

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to detect the expression of eukaryotic translation initiation factor 3B (EIF3B) and investigate its correlation with tumor features and survival in cervical cancer patients. METHODS: This study retrospectively reviewed 187 cervical cancer (squamous cell carcinoma) patients underwent tumor resection. Immunohistochemistry was performed to determine the expression of EIF3B in tissue samples. Besides, disease free survival (DFS) and overall survival (OS) were calculated. The median follow-up duration was 69 months, and the last follow-up date was 2017/12/31. RESULTS: EIF3B expression was higher in tumor tissue compared to paired adjacent tissue …(45.5% vs. 32.1%, P = 0.015). Besides, EIF3B high expression was associated with higher Federation of Gynecology and Obstetrics (FIGO) Stage (P = 0.001) and presence of lymph node metastasis (P = 0.002). As to survival profiles, Kaplan-Meier curves disclosed that DFS (P < 0.001) and OS (P < 0.001) were both shorter in EIF3B high expression group compared to EIF3B low expression group. Multivariate Cox’s regression analysis disclosed that EIF3B high expression, pathological grade III (vs I/II) and FIGO Stage III/IV (vs I/II) were independent predictive factors for unfavorable DFS as well as OS in cervical cancer patients (all P value < 0.05). CONCLUSION: EIF3B is overexpressed, and its high expression correlates with higher FIGO Stage, lymph node metastasis and unfavorable survival profiles in cervical cancer patients. Show more

Keywords: Eukaryotic translation initiation factor 3B (EIF3B), cervical cancer, survival, prognosis

DOI: 10.3233/CBM-182114

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 123-130, 2019

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

Article Type: Research Article

Abstract: BACKGROUND: The signaling adapter protein CrkL plays vital roles in multiple cancers. However, the expression pattern of CrkL protein and its clinical significance have not been well characterized in human gastric cancer (GC) so far. OBJECTIVE: To investigate the association of tissue-based CrkL protein expression level with the clinicopathological characteristics and prognosis of GC patients. METHODS: The expression level of CrkL protein in 380 GC patients was analyzed by immunohistochemistry. The associations of CrkL protein expression level with clinicopathologicalal characteristics and clinical outcome were evaluated. RESULTS: Compared with the matched …adjacent non-tumor tissues, CrkL protein expression level was significantly up-regulated in tumor tissues. In addition, there was a positive correlation between CrkL and Ki67 expression levels in GC patients. An elevated CrkL level statistically correlated with aggressive clinicopathologicalal characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Notably, multivariate analysis identified tissue-based CrkL level as an independent predictor for the unfavorable prognosis of GC. CONCLUSIONS: These results indicate that CrkL protein may serve as a novel prognostic biomarker in GC. Show more

Keywords: Gastric cancer, CrkL, tumorigenesis, immunohistochemistry, prognosis

DOI: 10.3233/CBM-192435

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 131-138, 2019

Authors: Ren, Xiaolu | Zhang, Yixun | Lyu, Yi | Jin, Baoli | Guo, Hongxia | Wu, Jing | Li, Xiaomin | Liu, Xuejun

Article Type: Research Article

Abstract: BACKGROUND: No tumor biomarker (TM) is available for de novo metastatic lung adenocarcinoma. OBJECTIVE: To examine the serum levels of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen (CA) 19-9, CA125, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), and lactate dehydrogenase (LDH) to predict de novo metastatic lung adenocarcinoma. METHODS: This was a retrospective study of geriatric (⩾ 60 years of age) patients with lung cancer diagnosed at Shanxi Cancer Hospital from 02/2012 to 12/2017. CEA, CYFRA21-1, CA199, NSE, CA125, TPA, and TPS were detected …by ELISA and LDH was detected by LDH kit. Their predictive value was assessed using receiver operating characteristic (ROC) curves and multivariable logistic regression. RESULTS: The positive rates of LDH and TMs were higher in the metastatic group (all P < 0.05). The best single TMs were CYFRA21-1 (70.5% sensitivity) and CA199 (92.0% specificity). When using any two, the best were CYFRA21-1+ TPA (77.1% sensitivity) and CA199+ TPA or NSE (both 84.1% specificity). High LDH and CA125 statuses were each independently associated with brain, bone, liver, and lung metastases (all P < 0.05). CONCLUSIONS: Abnormal level of LDH and TMs, alone or in combination, had predictive value for metastasis in geriatric patients with lung adenocarcinoma; these indicators were also associated with the metastatic site. Show more

Keywords: Lung adenocarcinoma, lactate dehydrogenase, tumor marker, metastasis, elderly

DOI: 10.3233/CBM-190201

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 139-150, 2019

Authors: Chen, Yan | Ye, Xiabin | Xia, Xuemei | Lin, Xuefang

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to explore the correlation of circular RNA ABCB10 (circ-ABCB10) expression with clinicopathological features and survival, as well as its impact on regulating cell proliferation and apoptosis in epithelial ovarian cancer (EOC). METHODS: A total of 103 EOC patients were consecutively recruited, then their tumor tissues were obtained for circ-ABCB10 detection using qRT-PCR. Additionally, 53 EOC adjacent tissues were collected as control. Patients’ clinicopathological and survival data were recorded. In vitro , circ-ABCB10 expression was detected in OVCAR3, UWB1.289, SKOV3, CAOV3 and IOSE80 cell lines by RT-qPCR, and the effect of circ-ABCB10 on …cell proliferation and apoptosis was detected through circ-ABCB10 overexpression and silencing by plasmids transfection into SKOV3 cells. RESULTS: Circ-ABCB10 was upregulated in tumor tissues compared with adjacent tissues, and presented with good value in distinguishing tumor tissues from adjacent tissues (AUC = 0.766, 95% CI: 0.690–0.842). Circ-ABCB10 high expression was correlated with poor differentiation, large tumor size and advanced International Federation of Gynecology and Obstetrics (FIGO) stage in EOC patients. As for survival, circ-ABCB10 was correlated with worse OS. In vitro experiments revealed that circ-ABCB10 was upregulated and promoted cell proliferation but reduced cell apoptosis, and negatively regulated miR-1271, miR-1252 and miR-203 in EOC cells. CONCLUSIONS: Circ-ABCB10 correlates with advanced clinicopathological features and unfavorable survival, and promotes proliferation, reduces apoptosis and negatively regulated miR-1271, miR-1252 and miR-203 in EOC. Show more

Keywords: Circ-ABCB10, EOC, disease risk, OS, cell proliferation and apoptosis

DOI: 10.3233/CBM-190064

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 151-161, 2019

Authors: Asanuma, Kunihiro | Nakamura, Tomoki | Asanuma, Yumiko | Kakimoto, Takuya | Yada, Yuki | Hagi, Tomohito | Kita, Kouji | Matsumine, Akihiko | Sudo, Akihiro

Article Type: Research Article

Abstract: BACKGROUND: Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin. OBJECTIVES: To clarify the correlation between serum TM levels and clinicopathological parameters. METHODS: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test …and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival. RESULTS: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p = 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p = 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1–3 (p = 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p = 0.0147; OS: HR 3.60, p = 0.0557) in grades 1–3. CONCLUSIONS: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy. Show more

Keywords: Thrombomodulin, soft tissue tumor, soft tissue sarcoma, metastasis, prognosis

DOI: 10.3233/CBM-182075

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 163-170, 2019

Authors: Wang, Xiaoqiong | Jin, Qiaozhi | Wang, Xue | Chen, Wubing | Cai, Zhiyi

Article Type: Research Article

Abstract: BACKGROUND: Increasing evidence shows that long non-coding RNAs (lncRNAs) play a key role in the development of various cancers. Zinc finger antisense 1 (ZFAS1 ) is a novel lncRNA with previously demonstrated associations with several types of cancer. Here we examined the expression and potential function of the ZFAS1 in nasopharyngeal carcinoma (NPC). METHODS: We detected ZFAS1 expression in GSE12452, a human microarray dataset, and NPC cell lines. Small interfering RNA against ZFAS1 was used to elucidate the cellular functions of ZFAS1 using MTT, colony formation, cell cycle, cell apoptosis, transwell …invasion and migration and western blot assays. An activator of the PI3K/AKT signaling pathway (740Y-P) was used to determine the contribution of PI3K/AKT. RESULTS: ZFAS1 was significantly upregulated in NPC tissues and cell lines. Silencing ZFAS1 significantly inhibited cell proliferation and invasion, arrested cell cycle progression and promoted cell apoptosis, as well as reduced epithelial–mesenchymal transition. Moreover, 740Y-P could rescue the effects of ZFAS1 knockdown on proliferation, apoptosis and invasion in 5-8F cells. CONCLUSIONS: ZFAS1 might play an oncogenic role in NPC and facilitate cell proliferation and invasion via the PI3K/AKT signaling pathway in NPC cells. Show more

Keywords: ZFAS1, nasopharyngeal carcinoma, EMT, apoptosis, p-AKT

DOI: 10.3233/CBM-182080

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 171-182, 2019

Authors: Jin, Wei | Han, Haiming | Liu, Dandan

Article Type: Research Article

Abstract: BACKGROUND: miR-539 functions as a tumor suppressor in many types of cancer. However, the role of miR-539 in gastric cancer remains unclear. The aim of this study is to investigate the clinical significance and functional role of miR-539 in gastric cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-539 in gastric cancer patients tissues and cells. We analyzed the association between miR-539 expression levels and clinicopathological features, as well as overall survival information with Kaplan-Meier survival curves and Cox regression analysis. The functional role of miR-935 on the …proliferation, migration, and invasion was also investigated by using miR-539 mimic or miR-539 inhibitor through CCK-8 assay, Transwell migration and invasion assays. The relationship between miR-539 and RUNX2 was verified by a dual luciferase assay. RESULTS: The expression of miR-539 was decreased in gastric cancer tissues and cell lines. Downregulation of miR-539 was closely associated with differentiation, lymph node metastasis, TNM stage, and poor survival outcome of gastric cancer patients. Furthermore, overexpression of miR-539 inhibited cell proliferation, migration, and invasion of gastric cancer cells. In addition, RUNX2 was a direct target of miR-539. CONCLUSION: Taken together, miR-539 may serve as a tumor suppressor for inhibiting cell proliferation, migration, and invasion by targeting RUNX2. Reduced expression of miR-539 is an independent prognostic factor in gastric cancer and may be a potential prognostic biomarker and miR-539/RUNX2 axis may serve as a potential therapeutic target for the treatment of gastric cancer. Show more

Keywords: miR-539, gastric cancer, prognosis, proliferation, migration, invasion

DOI: 10.3233/CBM-190384

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 183-191, 2019

Authors: Zheng, Chenghao | Guo, Kai | Chen, Binshen | Wen, Yong | Xu, Yawen

Article Type: Research Article

Abstract: OBJECTIVES: In men, human prostate cancer (PCa) has become the second most common cancer. miRNAs are short non-coding RNAs that can inhibit target gene mRNAs. Studies have showed that the alternation of miRNAs expression in cancer is relevant to pathogenesis of tumor. In present study, we aimed to investigate functions of miR-214-5p in PCa. MATERIALS AND METHODS: 10 paired human prostate tumor tissues and homologous para-tumor tissues were recruited, and the levels of miR-214-5p and CRMP5 were respectively determined by qRT-PCR assay. Luciferase activity analysis was performed to explore the regulation of CRMP5 mRNA 3’UTR by …miR-214-5p. Then, cell experiments, including cell proliferation, apoptosis, cell cycle, migration and colony formation ability, were performed after proper plasmids or RNAs transfection. RESULTS: In PCa tissues and cell lines, expression of miR-214-5p was decreased compared with para-tumor tissues or normal prostate epithelial cell lines. Luciferase activity assay showed a direct combination of miR-214-5p and CRMP5 mRNA 3’UTR, and indicated that the absence of miR-214-5p in PCa cells may contributes to a high level of CRMP5. Cell experiments showed that miR-214-5p can induce inhibition of tumor cell growth, migration and colony forming efficiency, promotion of apoptosis and G1-phase arrest, on the other hand, co-expression of CRMP5 somewhat counteracted these phenotype induced by miR-214-5p. CONCLUSION: Taken together, miR-214-5p shows tumor suppression effects in PCa cells. Loss expression of miR-214-5p in PCa increase levels of CRMP5 through regulating CRMP5 3’UTR, which could be a potential therapy target for PCa. Show more

Keywords: Human prostate cancer, miR-214-5p, CRMP5, cell proliferation, apoptosis, migration

DOI: 10.3233/CBM-190128

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 193-202, 2019

Authors: Jiao, Xuelong | Lu, Jie | Huang, Yichuan | Zhang, Jinna | Zhang, Hongmei | Zhang, Kejun

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the diagnostic and prognostic values of long non-coding RNA H19 (H19) in patients with papillary thyroid carcinoma (PTC). METHODS: This retrospective, nonrandomised study included 410 patients with PTC and 89 patients with benign thyroid nodes (BTN)who underwent standard total thyroidectomy. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect H19 expression in these tissues. The relationship between H19 expression and the patients’ clinicopathological factors, including histopathological characteristics of the tumour, diagnosis and prognosis was explored. RESULTS: Expression of H19 was lower in the PTC tissues (1.259 ± …1.15) compared to the BNT tissues (2.8347 ± 2.176) (p = 0.001). Low expression of H19 was associated with patient’s age, tumor size, extrathyroid extension, pathological lateral node metastasis (pN1b), histological aggressive type and poorer disease-free survival (p < 0.0001). The sensitivity for distinguishing PTC from benign was 81.3%. H19 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis. CONCLUSIONS: H19 may serve as a potential predictor of poor prognoses in patients with PTC. Show more

Keywords: Papillary thyroid carcinoma, diagnosis, prognosis, long non-coding RNA H19

DOI: 10.3233/CBM-190273

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 203-207, 2019

Authors: Gong, Zhitao | Hu, Guohua

Article Type: Research Article

Abstract: BACKGROUND: Downregulation of PCDH20 is frequently involved in tumorigenesis of many cancers, but the role of PCDH20 protein in hypopharyngeal squamous cell carcinoma (HSCC) is still unknown. OBJECTIVE: The aim of this study was to investigate the role of PCDH20 in hypopharyngeal squamous cell carcinoma (HSCC). METHODS: Immunohistochemistry (IHC) and qRT-PCR was carried out to estimate the expressions of PCDH20 protein and mRNA in HSCC tissues and adjacent non-tumor tissues. Correlation between the PCDH20 expression and clinicopathological characteristics was evaluated using chi-square test. Meanwhile, Kaplan-Meier method and log-rank test were applied to analyze …the overall survival. After transfection of PCDH20, the CCK8 assay, Cell migration assay and invasion assay were used to investigate the changes in the viability, migration and invasion of Fuda cells. The mechanisms by which reduced PCDH20 promote migration and invasion of Fuda cells were examined using western blotting. RESULTS: PCDH20 protein showed in tumor tissue low expression rates of 67.5% (54/80). The mRNA of PCDH20 indicated the consistent trend (80%, 8/10). Reduced PCDH20 expression was positively related to T stage and lymph node metastasis (P < 0.05). Patients with low levels of PCDH20 had worse overall survival compared with those with high PCDH20 levels (P < 0.001). The univariate Cox regression analysis described that lymph node metastasis (P = 0.043) and down-regulated PCDH20 expression (P = 0.045) were significantly prognostic factors.Multivariate analysis suggested that low PCDH20 expression (P = 0.015) were significantly independent prognostic factors for overall survival. PCDH20 in Fadu cells significantly inhibited cell viability, migration and invasion. Meanwhile, PCDH20 was involved in the disruption of HSCC progression through antagonizing its downstream Wnt/β -catenin signalling pathway. CONCLUSION: Our data highlight that the downregulated PCDH20 may serve as reliable diagnostic biomarker in HSCC. Show more

Keywords: PCDH20, hypopharyngeal squamous cell carcinoma, clinicopathological features, lymph node metastasis, prognostic

DOI: 10.3233/CBM-190442

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 209-217, 2019

Authors: Gupta, Chhavi | Su, Jian | Zhan, Min | Stass, Sanford A. | Jiang, Feng

Article Type: Research Article

Abstract: BACKGROUND: Analysis of molecular changes in sputum may help diagnose lung cancer. Long non-coding RNAs (lncRNAs) play vital roles in various biological processes, and their dysregulations contribute to the development and progression of lung tumorigenesis. Herein, we determine whether aberrant lncRNAs could be used as potential sputum biomarkers for lung cancer. METHODS: Using reverse transcription PCR, we measure expressions of lung cancer-associated lncRNAs in sputum of a discovery cohort of 67 lung cancer patients and 65 cancer-free smokers with benign diseases and a validation cohort of 59 lung cancer patients and 60 cancer-free smokers with …benign diseases . RESULTS: In the discovery cohort, four of the lncRNAs displayed a significantly different level in sputum of lung cancer patients vs. cancer-free smokers with benign diseases (all P < 0.001). From the four lncRNAs, three lncRNAs (SNHG1, H19, and HOTAIR) are identified as a biomarker panel, producing 82.09% sensitivity and 89.23% specificity for diagnosis of lung cancer. Furthermore, the biomarker panel has a higher sensitivity (82.09% vs. 52.24%, P = 0.02) and a similar specificity compared with sputum cytology (89.23% vs. 90.77%, P = 0.45). In addition, the lncRNA biomarker panel had a higher sensitivity (87.50% vs. 70.07%, p = 0.03) for diagnosis of squamous cell carcinoma compared with adenocarcinoma of the lung, while maintaining the same specificity (89.23%). The potential of the sputum lncRNA biomarkers for lung cancer detection is confirmed in the validation cohort. CONCLUSION: We have for the first time shown that the analysis of lncRNAs in sputum might be a noninvasive approach for diagnosis of lung cancer. Show more

Keywords: Diagnosis, lung cancer, sputum, lncRNA, biomarkers

DOI: 10.3233/CBM-190161

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 219-227, 2019

Authors: Huang, Ying | Xiao, Wenfeng | Jiang, Xiuli | Li, Honglei

Article Type: Research Article

Abstract: Colorectal cancer (CRC) is a common cause of cancer-related deaths worldwide. MicroRNA-935 (miR-935) has been reported to be involved in several cancers. In the present study, we aimed to investigate the role of miR-935 in the progression of CRC. The expression levels of miR-935 in CRC tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The prognostic significance of miR-935 was identified using Kaplan-Meier survival analysis and Cox regression assay. Cell proliferation capacity was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion capacities were determined by Transwell assay in CRC cells. Bioinformatics analysis and …luciferase reporter assays were used to confirm the direct target of miR-935. The expression of miR-935 was increased in CRC tissues and cells. Overexpression of miR-935 was significantly associated with lymph node metastasis and TNM stage. Overexpression of miR-935 in patients predicted shorter overall survival compared to low miR-935 expression. The expression of miR-935 was indicated to be an independent prognostic factor for CRC patients. In addition, overexpression of miR-935 in CRC cells promoted cell proliferation, migration, and invasion, whereas inhibition of miR-935 suppressed cell proliferation, migration, and invasion. Bioinformatics and luciferase assays revealed that INPP4A is a direct target of miR-935. Our findings suggest that miR-935 functions as an oncogene and promotes CRC progression. INPP4A is a potential target of miR-935. And miR-935 may represent a prognostic biomarker and potential therapeutic strategy for CRC treatment. Show more

Keywords: Colorectal cancer, microRNA-935, prognosis, proliferation, migration, invasion

DOI: 10.3233/CBM-190183

Citation: Cancer Biomarkers, vol. 26, no. 2, pp. 229-237, 2019