Cancer Biomarkers - Volume 17, issue 2

Authors: Wu, Jia-Zhu | Tian, Tian | Huang, Ying | Liang, Jin-Hua | Miao, Yi | Wang, Li | Xu, Ji | Qu, Xiao-Yan | Fan, Lei | Li, Jian-Yong | Xu, Wei

Article Type: Research Article

Abstract: BACKGROUND: Carbohydrate antigen 125 (CA-125) is one of the most common used tumor biomarkers in clinical practice. Previous studies showed an association of increased CA-125 levels with advanced characteristics and inferior outcome in non-Hodgkin lymphoma. OBJECTIVE: To identify the clinical significance of CA-125 in diffuse large B-cell lymphoma (DLBCL). METHODS: We retrospectively analyzed 181 patients with DLBCL with measured serum CA-125 concentration at diagnosis and follow-ups during the courses. Clinical significance of CA-125 was evaluated by assessing the association between CA-125 levels and clinical characteristics. RESULTS: CA-125 levels on admission …were positively correlated with serum lactate dehydrogenase, β2-microglobulin (β2-MG), serum ferritin (SF) and cavity effusion, while negatively correlated with serum albumen (ALB). During the courses, CA-125 levels were positively correlated with β 2-MG, SF and effusion, and negatively correlated with ALB. A better correlation between effusion and CA-125 levels was observed. Using a cut-off value > 50.39 U/ml gave a sensitivity of 73.8% and a specificity of 92.1% for the indication of effusion at diagnosis, while during the courses the sensitivity was much lower. On the prognostic role of CA-125, we found prognostic relevance on progression-free survival (PFS) but not on overall survival (OS). CONCLUSIONS: Our study revealed limited usefulness of CA-125 concentration at diagnosis and follow-ups in DLBCL. Show more

Keywords: CA-125, diffuse large B-cell lymphoma, serosal effusion, prognosis

DOI: 10.3233/CBM-160632

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 205-212, 2016

Authors: Meshkat, Mahboobeh | Tanha, Hamzeh Mesrian | Naeini, Marjan Mojtabavi | Ghaedi, Kamran | Sanati, Mohammad H. | Meshkat, Marzieh | Bagheri, Fatemeh

Article Type: Research Article

Abstract: In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR. Allelic and genotypic association and Armitage's trend tests were run to investigate the correlation between the alleles and genotypes and expressed phenotypes of BC. Bioinformatics analyses introduce regulatory …function of miR-146a-5p in numerous signaling pathways and impact of allele substitution upon mir-146a stem-loop stability. Logistic regression data represented the C allele of rs2910164 (OR = 4.00, p= 0.0037) as the risk allele and associated with Her2-positive phenotype. In a similar vein, data revealed the correlation of the C allele and cancer death less than two years in BC patients (OR = 2.65, p= 0.0217). Ultimately, unconditional logistical regression models suggested log-additive model for inheritance manner of rs2910164 in either Her2 status or BC survival (OR = 5.64, p= 0.0025 and OR = 3.13, p= 0.019, respectively). Using bioinformatics connected association of Her2 status to altered function of miR-146a-5p in regulation of focal adhesion and Ras pathway. Furthermore, computations inferred the association between death phenotype and studied SNP upon specific target genes of miR-146a-5p involved in focal adhesion, EGF receptor, Ras, ErbB, interleukin, Toll-like receptor, NGF, angiogenesis, and p53 feedback loops 2 signaling pathways. These verdicts may enhance our perceptions of how mir-146a rs2910164 affect expressed phenotypes in BC, and might have potential implications to develop BC treatment in future. Show more

Keywords: Breast cancer, cancer death, Her2, mir-146a, functional SNP

DOI: 10.3233/CBM-160633

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 213-222, 2016

Authors: Yang, Bing | Liu, Zheng | Ning, Hao | Zhang, Kai | Pan, Dongliang | Ding, Kejia | Huang, Wei | Kang, Xin-Li | Wang, Yang | Chen, Xiang

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the effects of microRNA-21 (miR-21) in peripheral blood mononuclear cells (PBMC) in the diagnosis and prognosis of prostate cancer (PCa). METHODS: Proved by pathologic biopsy, 92 patients diagnosed with PCa and also underwent resection operation and 85 patients with benign prostatic hyperplasia (BPH) were selected in this study, as well as 97 healthy volunteers were chosen as the control group. PBMC were extracted to examine the relative expression of miR-21 by real time reverse transcriptase-polymerase chain reaction (RT-PCR). The relative operating characteristic (ROC) curves were drew to analyze the diagnosis value of PCa. …The survival function curves were made by Kaplan-Meier method to show the miR-21 expression levels of PCa patients. The Log-rank test was adopted to compare the differences among the different groups. The Cox proportional hazard risk regression analysis was used to screen the independent factors affected the PCa patients. RESULTS: The expression levels of miR-21 in PCa group were increased compared to BPH and control group (P < 0.05). The expression of miR-21 was significantly correlated with the Gleason score, clinical stages, bone metastasis and tumor recurrence (all P < 0.05). ROC curves demonstrated that the area under the curve of PCa and BPH distinguished by the miR-21 were 0.974 and 95% confidence intervals (95% CI) were 0.956∼ 0.993. The sensitivity and specificity were 93.5% and 92.9%. ROC curves demonstrated that the area under the curve of PCa and control group distinguished by the miR-21 were 0.984 and 95% CI were 0.972∼ 0.997. The sensitivity and specificity were 94.6% and 92.8%. The results of Kaplan-Meier Method demonstrated that the miR-21 expression levels were related to the prognosis of PCa (all P < 0.05). The results of the COX analysis suggested that the miR-21 expression level, tumor recurrence and bone metastasis could be the independent factors affected the prognosis of PCa patients (all P < 0.05). CONCLUSION: miR-21 is highly expressed in the PCa patients, which could be the molecule biomarker of diagnosis and prognosis of PCa. Show more

Keywords: Prostate cancer, MicroRNA-21, peripheral blood mononuclear cells, benign prostatic hyperplasia, gleason scores, bone metastasis, tumor recurrences, specific antigen

DOI: 10.3233/CBM-160634

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 223-230, 2016

Authors: He, Anbang | Chen, Zhicong | Mei, Hongbing | Liu, Yuchen

Article Type: Research Article

Abstract: OBJECTIVE: In this study, we examined the relationships between the expression level of long non-coding RNA MIR31HG in bladder cancer and the clinical characteristics. METHODS: A total of 55 tissue samples from patients with bladder cancer were collected, and the lncRNA MIR31HG levels in cancer, paired non-cancer tissues and BC cell lines were detected by real-time quantitative RT-PCR (qRT-PCR). The relationships between MIR31HG level and the clinical characteristics were evaluated. RESULTS: MIR31HG expression was remarkably decreased in bladder cancer tissues compared with adjacent noncancerous tissues (P < 0.05). MIR31HG expression was also significantly …down-regulated in four bladder cancer cell lines (P < 0.001). Clinicopathologic analysis revealed that MIR31HG expression was negatively associated with TNM stage (P = 0.010), but not with other clinicopathological characteristics. CONCLUSIONS: These findings revealed that MIR31HG may function as a cancer-suppressor gene to participate in the bladder cancer carcinogenesis and development. Show more

Keywords: MIR31HG, LOC554202, bladder cancer, LncRNAs

DOI: 10.3233/CBM-160635

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 231-236, 2016

Authors: Yang, Jing | Wang, Rong | Li, Hongjiang | Lv, Qing | Meng, Wentong | Yang, Xiaoqin

Article Type: Research Article

Abstract: BACKGROUND: Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), a glycoprotein enriched on the plasma membrane of tumor cells, promotes proliferation, invasion, metastasis, and survival of malignant tumor cells. In this study, we sought to examine the expression of EMMPRIN in breast tumors, and to identify the potential roles of EMMPRIN on breast cancer cells. METHODS: EMMPRIN expression in breast cancer tissues was assessed by immunohistochemistry. We used a lentivirus vector-based RNA interference (RNAi) approach expressing short hairpin RNA (shRNA) to knockdown EMMPRIN gene in breast cancer cell lines MDA-MB-231 and …MCF-7. In vitro , Cell proliferative, invasive potential were determined by Cell Counting Kit (CCK-8), cell cycle analysis and matrigel invasion assay, respectively. In vivo , tumorigenicity was monitored by inoculating tumor cells into breast fat pad of female nude mice. RESULTS: EMMPRIN was over-expressed in breast tumors and breast cancer cell lines. Down-regulation of EMMPRIN by lentivirus vector-based RNAi led to decreased cell proliferative, decreased matrigel invasion in vitro , and attenuated tumor formation in vivo . CONCLUSION: High expression of EMMPRIN plays a crucial role in breast cancer cell proliferation, matrigel invasion and tumor formation. Show more

Keywords: EMMPRIN, MMP-9, breast cancer, RNA interference (RNAi), short hairpin RNA (shRNA), lentivirus

DOI: 10.3233/CBM-160636

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 237-247, 2016

Authors: Shi, Zuo-Wei | Wang, Jing-Lu | Zhao, Ning | Guan, Ying | He, Wen

Article Type: Research Article

Abstract: OBJECTIVE: To study the correlation between single nucleotide polymorphism (SNP) of hsa-miR-124a and risk and prognosis of osteosarcoma (OS). METHODS: OS patients (n = 174) hospitalized at The Second Affiliated Hospital of Harbin Medical University from January 2010 to March 2012 were selected as case group by inclusion and exclusion criteria, and healthy people (n = 150) receiving physical examination at the same duration were recruited as control group. Polymerase chain reaction-ligase detection reaction (PCR-LDR) was performed for genotyping of hsa-miR-124a rs531564. RESULTS: There were significant differences in the frequency …distribution of genotypes and alleles of hsa-miR-124a rs531564 in the case and control group (all P < 0.05); the individuals carrying with CG + GG genotype showed significantly decreased risk for OS. The clinical pathological characteristics were significantly different in the patients with CC genotype and CG + GG genotype, including tumor size, tumor differentiation grading, Enneking staging, operation manner, time of chemotherapy and metastasis (all P < 0.05). The 5-year survival rate of the cases with CC genotype was significantly lower than that of the ones with CG + GG genotype (P < 0.05). CG + GG genotype, Enneking staging and operation manner were independent risk factors for prognosis of OS (all P < 0.05). CONCLUSIONS: CG +$ GG genotype of hsa-miR-124a rs531564 had decreased risk for OS and affected prognosis of OS. Show more

Keywords: Osteosarcoma, single nucleotide polymorphism, hsa-miR-124a, rs531564, polymerase chain reaction ligase detection reaction, chemotherapy, risk, prognosis

DOI: 10.3233/CBM-160637

Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 249-257, 2016