Peng Qiliang, Cheng Ming, Li Ting, Chen Xiangying, Shen Yi, Zhu Yaqun, Xu Bo
1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
Cancer Cell Int. 2020 Feb 18;20:56. doi: 10.1186/s12935-020-1142-1. eCollection 2020.
Accumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial.
We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC.
Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01-1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein‑protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.
Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
越来越多的证据表明，微小RNA-200（miR-200a、miR-200b和miR-200c）可作为癌症预后有前景的分子生物标志物。然而，miR-200表达与结直肠癌（CRC）预后之间的关联仍存在争议。
我们应用荟萃分析和生物信息学分析相结合的两种主流方法，以回答miR-200是否与CRC患者的预后相关，以及miR-200为何可作为CRC的预后生物标志物。
因此，miR-200低表达与CRC患者不良总生存期（OS）相关（风险比：1.09；95%置信区间1.01 - 1.17；P = 0.025）。根据亚组分析，miR-200的预后作用在组织样本、大样本、美国患者和miR-200a亚组中更为显著。然后预测miR-200的靶基因并进行功能富集分析。结果表明，miR-200的靶基因主要富集到一些重要的本体主题，如调控能力、关键细胞结构和结合功能。此外，还鉴定出一系列重要的信号通路，它们与CRC的发生和进展显著相关。另外，构建了miR-200靶标的蛋白质-蛋白质相互作用（PPI）网络以筛选枢纽基因和模块。所鉴定的枢纽基因和模块被证实高度参与CRC的发生和发展。
目前的证据表明，miR-200可能是CRC预后有前景的生物标志物。然而，在miR-200应用于临床之前，这些发现仍需要更多大规模的前瞻性研究和生物学实验进行验证。
