Qiu Xiaonan, Zhu Haixia, Liu Sang, Tao Guoquan, Jin Jing, Chu Haiyan, Wang Meilin, Tong Na, Gong Weida, Zhao Qinghong, Qiang Fulin, Zhang Zhengdong
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
J Gastroenterol Hepatol. 2017 Apr;32(4):819-827. doi: 10.1111/jgh.13533.
In our previous study, we demonstrated that four microRNAs (miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non-invasive diagnostic biomarkers for gastric cancer (GC).
We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan-Meier curves and log-rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis.
The median of miRNA expression in paraffin-embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down-regulation of miR-26a and miR-148a was significantly associated with shorter OS of GC patients either in the test set (miR-26a: P = 0.009; miR-148a: P = 0.005) or the validation set (miR-26a: P = 0.011; miR-148a: P = 0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR-26a and miR-148a were independent prognostic factors for predicting OS of patients with GC (miR-26a: HR = 0.76, 95% CI = 0.61-0.94; miR-148a: HR = 0.73, 95% CI = 0.58-0.91). Furthermore, elevated expression of miR-26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC-803 cells compared with negative control groups (P < 0.05).
These findings supported miR-26a and miR-148a could serve as potential prognostic biomarkers for GC.
在我们之前的研究中,我们证实血浆和肿瘤组织中均下调的四种微小RNA(miRNA)(miR-26a、miR-142-3p、miR-148a和miR-195)是有前景的胃癌(GC)非侵入性诊断生物标志物。
我们使用定量逆转录聚合酶链反应来评估GC患者石蜡包埋手术标本中这四种miRNA的表达水平。应用Kaplan-Meier曲线和对数秩检验来预测miRNA与GC患者累积总生存期(OS)之间的相关性。此外,我们进行了体外实验,包括细胞增殖、迁移、侵袭、集落形成和凋亡实验。
以石蜡包埋组织中miRNA表达的中位数作为截断值,将患者分为高表达组或低表达组。在测试组(miR-26a:P = 0.009;miR-148a:P = 0.005)或验证组(miR-26a:P = 0.011;miR-148a:P = 0.024)中,miR-26a和miR-148a的下调均与GC患者较短的OS显著相关。当两组合并时,Cox回归分析表明miR-26a和miR-148a均为预测GC患者OS的独立预后因素(miR-26a:HR = 0.76,95%CI = 0.61 - 0.94;miR-148a:HR = 0.73,95%CI = 0.58 - 0.91)。此外,与阴性对照组相比,miR-26表达升高显著抑制MGC-803细胞的增殖、迁移、侵袭和集落形成,并诱导其凋亡(P < 0.05)。
这些发现支持miR-26a和miR-148a可作为GC潜在的预后生物标志物。