Cancer Biomarkers - Volume 25, issue 2

Authors: An, Jia-Xiang | Ma, Zhao-Sheng | Ma, Ming-Hui | Shao, Shuai | Cao, Fei-Lin | Dai, Dong-Qiu

Article Type: Research Article

Abstract: BACKGROUND: The microRNA plays an important role in tumor progression. MiR-1236-3p acts as a tumor suppressor in various malignancies. OBJECTIVE: The aim of present study was to explore the expression of miR-1236-3p in gastric cancer (GC) and its correlation with clinicopathological features, and evaluate the feasibility of using it as a prognostic biomarker in GC. METHODS: Seventy-six pairs of tissue specimens were collected from GC patients. MiR-1236-3p expression level was detected by using qRT-PCR. The diagnostic value of miR-1236-3p was evaluated by receiver operating characteristic curve, and Kaplan-Meier method was used to analyze …the overall survival. Prognosis analysis was performed using multivariate cox proportional hazards regression analysis. RESULTS: The expression of miR-1236-3p was significantly reduced in tumor tissues (P < 0.001). In addition, miR-1236-3p expression was correlated with TNM stage (P = 0.001), lymph node metastasis (P = 0.005) and differentiated degree (P = 0.001). The area under the curve was 0.7016, and its specificity and sensitivity were 60.53% and 73.68%. Kaplan-Meier survival curves showed that patients with high miR-1236-3p expression had better overall survival than those with low expression (P = 0.0190). Multivariate Cox regression analysis showed that the miR-1236-3p expression (P = 0.033) was an independent prognostic factor for overall survival of GC prognosis. CONCLUSIONS: The study showed that miR-1236-3p is downregulated in GC tissues, and low expression of miR-1236-3p is associated with a poor prognosis in GC. It may be a new diagnostic and prognostic biomarker for GC. Show more

Keywords: miR-1236-3p, biomarker, gastric cancer, diagnosis, prognosis

DOI: 10.3233/CBM-171026

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 127-132, 2019

Authors: Zou, Ting | Wang, Ping Ling | Gao, Yan | Liang, Wen Tong

Article Type: Research Article

Abstract: Long noncoding RNAs (LncRNAs) are involved in the occurrence and progression of human tumors including ovarian cancer (OC). Long noncoding RNA HOTTIP has been found to be involved in several human tumors development. However, the role of HOTTIP in OC remains large unknown. In the present study, our results observed that lncRNA HOTTIP expression levels were notably higher in ovarian cancer tissue samples compared to adjacent normal tissue samples. Increased lncRNA HOTTIP expression levels were significantly associated with advanced FIGO stage and lymph node metastasis of ovarian cancer patients. Survival plots analysis results showed high lncRNA HOTTIP expression levels in …ovarian cancer patients showed a poor prognosis compared to patients with low lncRNA HOTTIP expression levels. Function assays showed that lncRNA HOTTIP knockdown in ovarian cancer cells decreased cell proliferation and cell invasion capacities. Furthermore, we demonstrated that inhibition of lncRNA HOTTIP suppressed Wnt/β -catenin signaling by downregulating β -catenin expression. Thus, these results suggest that aberrant HOTTIP expression level could serve as a promising biomarker for monitoring ovarian cancer and potential target of ovarian cancer treatment. Show more

Keywords: Ovarian cancer, long noncoding RNA, HOTTIP, prognosis, cell proliferation

DOI: 10.3233/CBM-181727

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 133-139, 2019

Authors: Giotakis, Aris I. | Lazaris, Andreas C. | Kataki, Agapi | Kontos, Christos K. | Giotakis, Evangelos I.

Article Type: Research Article

Abstract: BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) constitutes the third most frequent head and neck cancer. Several tissue biomarkers have been studied for their prognostic significance in LSCC. OBJECTIVE: To investigate the prognostic significance of BCL2L12 , a new member of the BCL2 family, in primary LSCC along with well-examined biomarkers such as BCL2 and BAX . METHODS: Cancerous tissue specimens of patients with primary LSCC were collected during 2005 and 2012 as pretreatment tissue biopsy. The specimens were immunohistochemically evaluated for the protein expression of BCL2L12 , BCL2 and BAX …. Kaplan-Meier survival curves and Cox proportional hazard regression models were performed to evaluate prognosis. RESULTS: In the study cohort of 78 patients with primary LSCC, Kaplan-Meier survival curves demonstrated that advanced-stage LSCC patients with BCL2L12 -positive tumors had significantly higher OS time in comparison with advanced-stage LSCC patients with BCL2L12 -negative tumors (p = 0.014). Also, advanced-stage LSCC patients with BCL2L12 -positive tumors had significantly lower risk of death from LSCC compared to advanced-stage LSCC patients with BCL2L12 -negative tumors (HR = 0.228, 95%CI = 0.063–0.833, p = 0.025). CONCLUSIONS: BCL2L12 protein expression could be used as a favorable prognostic tissue biomarker in patients with primary advanced-stage LSCC. On the contrary, BCL2 and BAX did not correlate with prognosis in patients with primary LSCC. Show more

Keywords: Laryngeal neoplasms, BCL2L12, biomarkers, prognosis, survival

DOI: 10.3233/CBM-181772

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 141-149, 2019

Authors: Huang, Yong | Cen, Junjie | Wei, Jinhuan | Chen, Zhenhua | Fang, Yong | Feng, Zihao | Lu, Jun | Liang, Yanping | Luo, Junhang | Mo, Chengqiang | Chen, Wei

Article Type: Research Article

Abstract: BACKGROUND: Amplified in breast cancer 1 (AIB1) is a candidate oncogene in human breast cancer, which has been identified to be amplified and overexpressed in several types of other human cancers. Abnormalities of AIB1 and its clinical/prognostic significance, however, in upper tract urothelial carcinoma (UTUC) remain unclear. OBJECTIVE: To explore what role AIB1 plays in upper tract urothelial carcinoma. METHODS: The expression of AIB1 was analyzed using immunohistochemical staining in 133 UTUC patients. Overall, cancer specific and recurrence-free survival rates (OS, CSS, and RFS) were estimated using the Kaplan-Meier method. Multivariable COX regression …models containing relevant clinicopathological variables addressed the prediction of postoperative outcome. RESULTS: High AIB1 expression was observed to be associated with increased hazard ratios for 5-year CSS (80.6% vs. 55.8%, p = 0.008) and OS (78.1% vs. 54.8%, p = 0.006). Multivariable analysis revealed that elevated AIB1 expression was an independent prognostic predictor of OS, CSS and RFS. Additionally, pT, pN and hydronephrosis were independently associated with oncologic outcome of UTUC. Three proposed nomograms were proposed to provide an individualized risk estimate of postoperative outcome in patients with UTUC. CONCLUSIONS: AIB1 can be used as an independent molecular marker for the prognosis of clinical outcomes of UTUC. Show more

Keywords: AIB1, immunohistochemistry, prognosis, upper tract urothelial carcinoma

DOI: 10.3233/CBM-182020

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 151-160, 2019

Authors: Wu, Zhun | Huang, Wei | Chen, Yuedong | Chen, Bin | Liu, Rongfu | Bai, Peide | Xing, Jinchun

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/CBM239001.

Keywords: Prostate carcinoma, LINC01638 lncRNA, notch1

DOI: 10.3233/CBM-182137

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 161-168, 2019

Authors: Zhu, Linwen | Li, Tianwen | Shen, Yijing | Yu, Xiuchong | Xiao, Bingxiu | Guo, Junming

Article Type: Research Article

Abstract: BACKGROUND: tRNA halves (tiRNAs) are produced from mature tRNAs. They have important roles both with in normal cells and cancer cells. However, the diagnostic value of tiRNAs in cancers have not yet been elucidated. OBJECTIVE: To explore the diagnostic value of tiRNA-5034-GluTTC-2 in gastric cancer. PATIENTS AND METHODS: Quantitative reverse transcription-polymerase chain reaction was used to detect the expression levels of tiRNA-5034-GluTTC-2 in paired gastric cancer tissues and adjacent normal tissues, plasmas from patients with gastric cancer and healthy people, and gastric cancer cell lines. Then, the relationship between its levels and clinicopathological …factors of patients with gastric cancer was analyzed. A receiver operating characteristic (ROC) curve was established to predict the diagnostic value. RESULTS: tiRNA-5034-GluTTC-2 was first found to be down-regulated in gastric cancer tissues and plasmas. Its levels were significantly associated with tumor size. The area under the ROC curve (AUC) was 0.779 and 0.835 in tissue and plasma, respectively. The sensitivity, specificity and AUC were 84.7%, 92.8%, and 0.915 when tissues and plasmas were used in combination, respectively. The overall survival rate of patients with a lower expression of tiRNA-5034-GluTTC-2 was significantly lower than those with a higher expression. CONCLUSIONS: These results indicated that tiRNA-5034-GluTTC-2 may be a novel biomarker for the diagnosis of gastric cancer. Show more

Keywords: tRNA halves, tiRNA-5034-GluTTC-2, biomarker, gastric cancer, diagnosis

DOI: 10.3233/CBM-182184

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 169-176, 2019

Authors: Serilmez, Murat | Özgür, Emre | Karaman, Sule | Gezer, Ugur | Duranyıldız, Derya

Article Type: Research Article

Abstract: BACKGROUND: Reseptor tyrosine kinases (cMET and EGFR) are important in lung cancer targeted therapy. We believe if we can use them as markers for clinicians to help decide the diagnosis of lung cancer. This parameter will be important in serum samples of patients with lung cancer diagnosis and treatment. The aim of this study is aimed to evaluate the clinical utility of serum protein and circulating mRNA of cMET and HGF in lung cancer patients. We also analyzed the correlation of mRNA expression with clinicopathologic parameters. METHODS: We performed enzyme-linked immunosorbent assay (ELISA) to measure and …compare serum protein and circulating mRNA of cMET and HGF levels in peripheral blood from 60 lung cancer patients and 40 healthy control group. RESULTS: We found that both protein and gene expression levels of serum c-MET, HGF and EGFR were significantly higher in patients with lung cancer than control group. There was no association between HGF, cMET, EGF, EGFR (both protein and gene) expression levels with age, gender, smoking habit, COPD, pathological types or tumor size, stage, metastatic-non metastatic adenocarcinoma-squamous carcinoma, SCLC-NSCLC. As a result of ROC analysis, serum cMET (AUC: 0.892) and HGF protein (AUC: 0.784) were diagnosed in lung cancer patients (Fig. 1 ). The AUC values of serum EGF and EGFR proteins were calculated to be 0.631 and 0.692, respectively. CONCLUSION: To our knowledge this is the first study comparing the levels of protein and mRNA in the serum material of HGF, c-MET, EGF and EGFR parameters in lung cancer patients’ blood samples. Further prospective studies with more participants for better understanding of mechanism and effect for HGF and c-MET inhibitors in lung cancer will help us to identify of these biomarkers role for guiding us to sellect individualized itargeted therapies. Show more

Keywords: Reseptor tyrosine kinases, growth factors, lung cancer

DOI: 10.3233/CBM-182231

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 177-184, 2019

Authors: Li, Yi | Su, Xiaomei | Pan, Haixia

Article Type: Research Article

Abstract: BACKGROUND: The PANDAR, a novel identified long non-coding RNA, is previously reported to function as oncogene in various cancers including breast cancer. the study aims to explore the role of lncRNA PANDAR for cell proliferation and invasion of breast cancer, and its underlying mechanism. METHODS: The expression of lncRNA PANDAR in 65 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) assay. The association between lncRNA PANDAR expression and clinical factors of breast cancer was analyzed. Cell proliferation, cell colony formation and cell invasion assays were performed …to detect the effects of lncRNA PANDAR expression tumor proliferation and invasion abilities. The western blot analysis was also performed to detected the EMT related makers expression of E-cadherin, Vimentin, MMP2 and MMP9. RESULTS: We demonstrated that lncRNA PANDAR expression was higher in breast cancer tissues and cells compared with adjacent normal tissues and the normal mammary epithelial cell line, respectively. Higher lncRNA PANDAR expression positively associated with lymph node metastasis and advanced clinical stage in patients. In vitro, we demonstrated that knockdown of lncRNA PANDAR significantly suppressed cell proliferation, cell colony formation and cell invasion ability in breast cells. Furthermore, we verified that knockdown of lncRNA PANDAR dramatically inhibited cell epithelial-mesenchymal transition (EMT) pathway by downregulating Vimentin, MMP2 and MMP9 expression, but upregulating E-cadherin expression in breast cancer. CONCLUSIONS: Our results proved that PANDAR may serve as potential target of breast cancer treatment. Show more

Keywords: Long non-coding RNA, PANDAR, cell proliferation, cell invasion, epithelial-mesenchymal transition

DOI: 10.3233/CBM-182251

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 185-192, 2019

Authors: Xu, Jin-huan | Wang, Yan | Xu, Dong

Article Type: Research Article

Abstract: Circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but its functional effects in breast cancer (BC) remains largely unclear. In this study, we aimed to explore the expressing pattern, clinical significance and potential function of a newly identified circRNA, hsa_circ_001569, in BC. RT-PCR was performed to detect the expression of hsa_circ_001569 in both BC tissues and cell lines. The associations between hsa_circ_001569 expression and clinicopathological features and prognosis in BC patients were statistically analyzed. Next, we investigated the effects of hsa_circ_001569 on the proliferation, apoptosis, migration and invasion in BC cells lines. The effects of abnormal hsa_circ_001569 …expression on EMT pathway and PI3K/AKT pathway were determined using Western blot. We found that hsa_circ_001569 expression was significantly up-regulated in both BC tissues and cell lines. Overexpression of hsa_circ_001569 was associated with Lymph node metastasis, advanced clinical stage and shorter overall survival. Multivariate assay confirmed that hsa_circ_001569 expression was an independent prognostic factor for 5-year overall survival. Furthermore, functional investigations revealed that knockdown of hsa_circ_001569 significantly suppressed the growth and metastatic potentials of BC cells. Besides, molecular mechanistic study revealed that depression of hsa_circ_001569 impeded the activation of PI3K-AKT signaling in BC cells. Our results indicated that hsa_circ_001569 upregulation was associated with BC lymph-node metastasis, clinical stage, and poor prognosis. Hsa_circ_001569 might contribute to progression of BC by modulating PI3K-AKT pathway. Show more

Keywords: Circular RNAs, hsa_circ_001569, breast cancer, metastasis, prognosis, PI3K/AKT pathway

DOI: 10.3233/CBM-182293

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 193-201, 2019

Authors: Kuang, Shihang | Li, Huafu | Feng, Jianhua | Xu, Sijun | Le, Youwei

Article Type: Research Article

Abstract: BACKGROUND: This study aimed to investigate the correlation of BRCA2 gene mutation and prognosis as well as variant genes in patients with invasive urothelial carcinoma of the bladder. It predicted and explored the possible mechanism and clinical value of BRCA2 in the occurrence and development of tumors. METHODS: Data sets of patients with bladder cancer were collected from the Cancer Genome Atlas (TCGA) database. Also the gene expression profile data and clinical information of the BRCA2 mutation group and non-BRCA2 mutation group were downloaded. RESULTS: The prognosis of the BRCA2 mutation group was …better than that of the non-mutant group. Among the down-regulated genes, the following genes showed significant differences between the two groups: CCL22, CYP2B6, CYP2E1, CYP4F2, HTR1E, HTR1F, KLRC1, NAPSA, SELL, SFTPA1, SFTPA2, SFTPB, SFTPC and STRA8, while the following genes among the up-regulated genes showed significant differences between the two groups: ELAVL3, NOTUM, TRH and VIP. Meanwhile, the following gene sets were highly enriched in BRCA2: cell cycle, DNA replication, homologous recombination, oocyte meiosis, ubiquitin-mediated proteolysis, base excision repair, progestin mediated oocyte maturation, basal transcription factor, biosynthesis of N polysaccharide, mismatch repair, sliceosome, purine metabolism as well as P53 and neurotrophic factor signaling pathway, etc. CONCLUSION: These findings suggested that the BRCA2 gene mutation is a good prognostic factor and can be used as a gene to predict the prognosis in the bladder cancer patients. Show more

Keywords: BRCA2 gene mutation, invasive urothelial carcinoma, bladder cancer

DOI: 10.3233/CBM-182379

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 203-212, 2019

Authors: Lampropoulou, Dimitra-Ioanna | Aravantinos, Gerasimos | Katifelis, Hector | Lazaris, Foivos | Laschos, Konstantinos | Theodosopoulos, Theodosios | Papadimitriou, Christos | Gazouli, Maria

Article Type: Research Article

Abstract: BACKGROUND : Colorectal cancer is the fourth cause of cancer related death. Drug resistance and toxicity remain major clinical issues. HOTAIR and MALAT1 are long non-coding RNAS that affect cellular proliferation, apoptosis and drug resistance; their up-regulation has been linked with a poor prognosis. OBJECTIVE: Investigation of the association between rs4759314 HOTAIR and rs3200401 MALAT1 polymorphisms and irinotecan-based chemotherapy in terms of drug efficacy and toxicity. METHODS: Samples from 98 patients receiving different regimens of irinotecan-based therapy were included. Efficacy and toxicity were evaluated. KRAS mutation, rs3200401 HOTAIR …and rs4759314 MALAT1 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR. RESULTS: Neither rs3200401 MALAT1 nor rs4759314 HOTAIR polymorphism are associated with response to treatment regimens. Rs4759314 was also not associated with increased toxicity in patients receiving irinotecan-based regimens. CT genotype of rs3200401 was associated with significantly reduced overall survival. An association between KRAS mutation and AG/GG genotypes in the rs4759314 was detected. CONCLUSIONS: CT genotype of rs3200401 MALAT1 polymorphism could serve as a toxicity biomarker. Carriers of the G allele of the rs4759314 HOTAIR are more likely to be carriers of KRAS mutations too. However, further studies in larger patient populations are required. Show more

Keywords: CRC, lncRNA, HOTAIR, MALAT1, rs3200401, rs4759314 irinotecan, drug resistance, toxicity

DOI: 10.3233/CBM-182383

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 213-221, 2019

Authors: Gondkar, Kirti | Patel, Krishna | Krishnappa, Shobha | Patil, Akkamahadevi | Nair, Bipin | Sundaram, Gopinath Meenakshi | Zea, Tan Tuan | Kumar, Prashant

Article Type: Research Article

Abstract: BACKGROUND: Transcription factors are commonly deregulated in various cancers. Here, we evaluated role of ELF3 in pathogenesis of bladder carcinoma (BCa). MATERIALS AND METHODS: We confirmed ELF3 expression pattern in BCa cell lines using western blot; and in different grades of tumors using Immunohistochemistry. Cell invasion assay was employed to demonstrate potential role of ELF3 in EMT. RESULTS AND CONCLUSION: ELF3 showed selective expression in low-grade cell lines and tumor tissues. Overexpression of ELF3 in mesenchymal cell line UMUC3 resulted in reduced invasion and decreased expression of mesenchymal markers. We observed association of …low ELF3 expression with increased risk and overall poor survival using publicly available data. ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer. Show more

Keywords: EMT, bladder cancer, ETS transcription factor

DOI: 10.3233/CBM-190013

Citation: Cancer Biomarkers, vol. 25, no. 2, pp. 223-232, 2019