Cancer Biomarkers - Volume 27, issue 2

Authors: Wei, Juan | Wei, Wei | Xu, Hanfeng | Wang, Zhaojing | Gao, Wen | Wang, Tianjun | Zheng, Qin | Shu, Yongqian | De, Wei

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNA) play key regulatory roles in cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we found circRNA102958 was up-regulated in gastric cancer tissues and cell lines. METHODS: The hsa_circRNA_102958 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue and cell. Then, the association between the expression level of hsa_circRNA_102958 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of hsa_circRNA_102958-miRNA-mRNA interactions was predicated. RESULTS: In this study, we …analyzed 30 patients and found that hsa_circRNA_102958 was significantly overexpressed in gastric cancer tissues compared with paired adjacent normal tissues. Clinicopathological features showed that hsa_circRNA_102958 level in GC tissues was positively associated with TNM stage (p = 0.032). The area under the ROC curve was 0.74. Finally, a total of 5 miRNAs were predicted to have an interaction with hsa_circRNA_102958. CONCLUSIONS: hsa_circRNA_102958 may be a potential novel and stable biomarker for the diagnosis of gastric carcinoma. Show more

Keywords: Gastric cancer, hsa_circRNA_102958, diagnosis, miRNA, mRNA

DOI: 10.3233/CBM-182029

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 139-145, 2020

Authors: Fu, Yongxing | Li, Yuanyuan | Wang, Xiaoyan | Li, Feng | Lu, Yugang

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-425-5p (miR-425-5p) has been investigated in some human cancers, but the understanding of its clinical and functional roles in non-small cell lung cancer (NSCLC) remains poor. OBJECTIVE: This study sought to measure the expression of miR-425-5p in NSCLC samples, assess its prognostic significance in cancer patients, and explore its functional role during tumor progression. METHODS: Expression of miR-425-5p was examined using quantitative Real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox analysis were conducted to evaluate the prognostic value of miR-425-5p. The effects of miR-425-5p on NSCLC cell proliferation, migration and …invasion were assessed using cell experiments. RESULTS: Expression of miR-425-5p was upregulated in NSCLC tissues and cells compared with the normal controls (all P < 0.05). The increased miR-425-5p expression was associated with positive lymph node metastasis and TNM advanced stage of the patients (all P < 0.05). The survival curves and Cox analysis indicated that high miR-425-5p was correlated with poor overall survival and acted as an independent prognostic factor in NSCLC patients. Cell experiments suggested that miR-425-5p overexpression could enhance, whereas its reduction could suppress NSCLC cell proliferation, migration and invasion (all P < 0.05). Forhead box J3 (FOXJ3) was proved to be a direct target of miR-425-5p in NSCLC. CONCLUSIONS: Overexpression of miR-425-5p predicts poor prognosis of NSCLC and promotes cancer cell proliferation, migration and invasion by targeting FOXJ3. Show more

Keywords: MiR-425-5p, prognosis, tumor progression, non-small cell lung cancer

DOI: 10.3233/CBM-190782

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 147-156, 2020

Authors: Aref, Salah | El Agdar, Mohammed | Salama, Osama | Zeid, Tarek Abouzeid | Sabry, Mohamed

Article Type: Research Article

Abstract: BACKGROUND: This study aimed to determine the prevalence and clinical impact of neurogenic locus notch homolog protein 1 (NOTCH1) mutations among patients with T cell acute lymphoblastic leukemia (T-ALL). PATIENT AND METHODS: A cohort of 60 T-ALL cases was included in this study. Sanger sequencing were done for NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline, glutamic acid, serine, threonine (PEST) domains in all studied T ALL patients at diagnosis. RESULTS: NOTCH1 mutations was detected …in 40 out of 60 T-ALL patients (66%). Mutations in T-ALL patients are deletions (22 mutations) and point mutation (10 mutations). NOTCH1 mutations was found to have no significant impact on clinical outcome and prognosis in T-ALL including overall survival, progression free survival, relapse and mortality (P > 0.05 for all). CONCLUSION: NOTCH1 mutations were frequently detected in T All patients; however, these mutations did not affect the T ALL patient’s outcome. The high prevalence of NOTCH1 mutations at diagnosis could be used for detection of minimal residual disease in T ALL. Show more

Keywords: NOTCH1, mutations, T-ALL, prognosis

DOI: 10.3233/CBM-190967

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 157-162, 2020

Authors: Chang, Liang-Che | Fan, Chung-Wei | Tseng, Wen-Ko | Hua, Chung-Ching

Article Type: Research Article

Abstract: BACKGROUND: Both mitochondria and the Nrf2/Keap1 pathway are targets of cancer therapy. Reactive oxygen species released from mitochondria can activate Nrf2, and the Nrf2/Keap1 pathway affects glycolysis, oxidative phosphorylation, mitochondrial biogenesis and mitophagy. OBJECTIVE: This study investigates the associations between the expressions of proteins in the Nrf2/Keap1 pathway and those related to mitochondrial function and glycolysis in colorectal cancer (CRC) with or without metastasis. METHODS: The protein levels of HO1, Nrf2, Keap1, Bach1, p21, p62, NRF1, LC3, ATP5B, HSP60 and GAPDH in the normal and tumor tissues of 60 CRC subjects were determined …by Western blot. RESULTS: The Keap1 protein levels, the ATP5B/HSP60 ratio and the BEC index were higher in the tumor than in the normal tissues of CRC with or without metastasis. The following clusters were found in the dendrogram: Nrf2 and p21 with ATP5B and GADPH in all the tissues and with NRF1 in all except the tumor tissues with metastasis; Bach1 with ATP5B and GAPDH in the tumor tissues; Keap1 with p62 in all the tissues, with LC3 in the tumor tissues and with NRF1 and HO1 in the tumor tissues with metastasis. CONCLUSIONS: Nrf2, Keap1, Bach1 and p21 have the association with the proteins related to mitochondrial functions different among the tissues of CRC with or without metastasis. Show more

Keywords: Colorectal cancer, metastasis, mitochondria, Nrf2/Keap1 pathway

DOI: 10.3233/CBM-190828

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 163-171, 2020

Authors: Gao, Ruixiang | Wang, Zhen | Liu, Qiang | Yang, Chunmei

Article Type: Research Article

Abstract: BACKGROUND: Esophageal cancer is a common tumor with high mortality worldwide. In the present study, we aimed to investigate the prognostic significance and regulatory effects of miR-105 on cellular functions of esophageal cancer cells. METHODS: The expression level of miR-105 was analyzed in esophageal cancer tissues and cell lines by qRT-PCR. Survival analysis was carried out using the Kaplan-Meier and the prognostic significance of miR-105 was analyzed with Cox regression analysis. The effects of miR-105 on cell proliferation, migration, and invasion abilities were detected with cellular experiments. RESULTS: We found that miR-105 was …significantly upregulated in esophageal cancer tissues and cell lines, compared with the control group, respectively. Moreover, overexpression of miR-105 was significantly associated with positive lymph node metastasis, advanced TNM stage, and poor overall survival. In addition, overexpression of miR-105 promoted cell proliferation, migration, and invasion in esophageal cancer cells, while downregulation of miR-105 suppressed these cellular behaviors. CONCLUSION: Our findings indicate that a higher level of miR-105 predicts poorer prognosis in esophageal cancer patients, and miR-105 can promote esophageal cancer cell proliferation, migration, and invasion. Show more

Keywords: MicroRNA-105, esophageal cancer, prognosis, proliferation, migration, invasion

DOI: 10.3233/CBM-190736

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 173-180, 2020

Authors: Petrozza, Vincenzo | Costantini, Manuela | Tito, Claudia | Giammusso, Laura Maria | Sorrentino, Veronica | Cacciotti, Jessica | Porta, Natale | Iaiza, Alessia | Pastore, Antonio Luigi | Di Carlo, Angelina | Simone, Giuseppe | Carbone, Antonio | Gallucci, Michele | Fazi, Francesco

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management. OBJECTIVE: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment. METHODS: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up …of 21 ccRCC patients by RTqPCR. RESULTS: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy. CONCLUSIONS: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up. Show more

Keywords: microRNA, miRNA, ccRCC, Cancer biomarkers, Liquid biopsy, metastasis, m miR-210

DOI: 10.3233/CBM-190242

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 181-188, 2020

Authors: Ye, Shuang | Liu, Shuai | Zhou, Shuling | Xiang, Libing | Wu, Xiaohua | Yang, Huijuan

Article Type: Research Article

Abstract: BACKGROUND: Ovarian clear cell carcinoma (CCC) is enriched in genes associated with glucose metabolism. OBJECTIVE: To evaluate the 18 F-FDG PET/CT-based metabolic variables and the correlations with clinicopathologic features in OCCC patients. METHODS: We measured quantitative parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). RESULTS: A total of 22 patients were included. PET/CT-based metabolic parameters were calculated for 20 patients because two had low glucose-uptake tumor. The median SUVmax was 7.25 (range 2.50–14.80). Spearman’s correlation test revealed that the …level of pre-operative serum cancer antigen 125 (CA 125) correlated significantly with MTV (P = 0.020) and TLG (P = 0.023). Interestingly, platinum-sensitive patients tended to have higher MTV/TLG though significance not achieved. On univariate analysis, the following four variables (stage, residual disease, platinum sensitivity and MTV50) were significant for both progression-free survival and overall survival. Besides, four metabolic parameters (MTV40, TLG40, TLG50 and TLG60) were significantly associated with patients’ overall survival. Out of expectation, ovarian CCC patients with higher level of MTV/TLG tended to have better survival. CONCLUSIONS: 18 F-FDG PET/CT-based metabolic volumetric parameters might be predicators for survival in ovarian CCC patients. Cautions should be taken when interpreting the results due to the small sample size. Show more

Keywords: Ovarian clear cell carcinoma, 18F-FDG PET/CT, metabolic tumor volume, total lesion glycolysis, prognosis

DOI: 10.3233/CBM-190904

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 189-194, 2020

Authors: Hu, Ying | Guo, Geyang | Li, Junjun | Chen, Jie | Tan, Pingqing

Article Type: Research Article

Abstract: BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer around the world. The aim of this study was to seek the long non-coding RNAs (lncRNAs) acting as diagnostic and prognostic biomarker of HNSCC. METHODS: Base on TCGA dataset, the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified between HNSCC and normal tissue. The machine learning and survival analysis were performed to estimate the potential diagnostic and prognostic value of lncRNAs for HNSCC. We also build the co-expression network and functional annotation. The expression of selected candidate mRNAs and …lncRNAs were validated by Quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 3363 DEmRNAs (1822 down-regulated and 1541 up-regulated mRNAs) and 32 DElncRNAs (13 down-regulated and 19 up-regulated lncRNAs) between HNSCC and normal tissue were obtained. A total of 13 lncRNAs (IL12A.AS1, RP11.159F24.6, RP11.863P13.3, LINC00941, FOXCUT, RNF144A.AS1, RP11.218E20.3, HCG22, HAGLROS, LINC01615, RP11.351J23.1, AC024592.9 and MIR9.3HG) were defined as optimal diagnostic lncRNAs biomarkers for HNSCC. The area under curve (AUC) of the support vector machine (SVM) model, decision tree model and random forests model and were 0.983, 0.842 and 0.983, and the specificity and sensitivity of the three model were 95.5% and 96.2%, 77.3% and 97.6% and 93.2% and 97.8%, respectively. Among them, AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also related to survival time. The focal adhesion, ECM-receptor interaction, pathways in cancer and cytokine-cytokine receptor interaction were four significantly enriched pathways in DEmRNAs co-expressed with the identified optimal diagnostic lncRNAs. But for most of the selected DEmRNAs and DElncRNAs, the expression was consistent with our integrated analysis results, including LINC00941, LINC01615, FOXCUT, TGA6 and MMP13. CONCLUSION: AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also were a prognostic lncRNAs biomarkers. Show more

Keywords: Head and neck squamous cell carcinoma, diagnostic, prognostic, machine learning

DOI: 10.3233/CBM-190694

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 195-206, 2020

Authors: Pagaza-Straffon, Cecilia | Marchat, Laurence A. | Herrera, Luis | Díaz-Chávez, José | Avante, Mauricio González | Rodríguez, Yadira Palacios | Arreola, Mauricio Castañón | López-Camarillo, César

Article Type: Brief Report

Abstract: BACKGROUND: Recent studies indicate that serum from cancer patients contains auto-antibodies against oncoproteins so called tumor-associated antigens (TAAs), which represent promising diagnostic and prognostic biomarkers. OBJECTIVES: In this study we searched for breast cancer-associated auto-antibodies against individual TAAs. Also we evaluated if a panel of multiple TTAs would improve the detection of auto-antibodies. We screened CEA, CCBN1, c-Myc, p53, Ki-67, Nm23, PRDX6, eIF5A, PARK7, GLIO-1, Hsp27 and Hsp70 proteins, previously detected as up-regulated in breast tumors of Mexican patients. METHODS: Enzyme-linked immunosorbent assays (ELISA) were performed to detect auto-antibodies in sera from a …cohort of 104 breast cancer patients and 50 sera from healthy individuals. RESULTS: Our data showed that antibodies frequency to any individual TAA was low and ranged from 0.96% to 4.8%. However, the successive addition of multiple TAAs represented by panels of three-to-five TAAs resulted in increased ELISA positive reactions. The first panel of three combined TAAs (p53/PRDX6/CEA) had a sensitivity of 19%, while a second set of four TAAs (p53/PRDX6/c-Myc/Hsp70) reached 28% sensitivity. Likewise, a third panel of five antigens (p53/PRDX6/c-Myc/Hsp70/Nm23) showed 34% sensitivity. CONCLUSIONS: Our data showed that detection of individual autoantibodies against TAAs in the cohort of patients analyzed here was low, which was enhanced by adding multiple TAAs. Data support the notion that frequencies of autoantibodies could be impacted by geographical and heterogeneous genetic factors of breast cancer patients. Show more

Keywords: Breast cancer, tumor-associated antigens, autoantibodies, immunodiagnosis

DOI: 10.3233/CBM-190708

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 207-211, 2020

Authors: Liu, Jinhui | Li, Siyue | Lin, Lijuan | Jiang, Yi | Wan, Yicong | Zhou, Shulin | Cheng, Wenjun

Article Type: Research Article

Abstract: Cervical cancer (CC) is one kind of female cancer. With the development of bioinformatics, targeted specific biomarkers therapy has become much more valuable. GSE26511 was obtained from gene expression omnibus (GEO). We utilized a package called “WGCNA” to build co-expression network and choose the hub module. Search Tool for the Retrieval of Interacting Genes Database (STRING) was used to analyze protein-protein interaction (PPI) information of those genes in the hub module. A Plug-in called MCODE was utilized to choose hub clusters of PPI network, which was visualized in Cytoscape. Clusterprofiler was used to do functional analysis. Univariate and multivariate cox …proportional hazards regression analysis were both conducted to predict the risk score of CC patients. Kaplan-Meier curve analysis was done to show the overall survival. Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the predictive value of the patient outcome. Validation of the hub gene in databases, Gene set enrichment analysis (GSEA) and GEPIA were completed. We built co-expression network based on GSE26511 and one CC-related module was identified. Functional analysis of this module showed that extracellular space and Signaling pathways regulating pluripotency of stem cells were most related pathways. PPI network screened GNG11 as the most valuable protein. Cox analysis showed that ACKR1 was negatively correlated with CC progression, which was validated in Gene Expression Profiling Interactive Analysis (GEPIA) and datasets. Survival analysis was performed and showed the consistent result. GSEA set enrichment analysis was also completed. This study showed hub functional terms and gene participated in CC and then speculated that ACKR1 might be tumor suppressor for CC. Show more

Keywords: Bioinformatics analysis, lymph node metastasis, atypical chemokine receptor 1 (ACKR1), cervical cancer

DOI: 10.3233/CBM-190533

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 213-223, 2020