Peng Qiliang, Feng Zhengyang, Shen Yi, Zhu Jiahao, Zou Li, Shen Yuntian, Zhu Yaqun
1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China.
2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
Cancer Cell Int. 2019 Jul 15;19:181. doi: 10.1186/s12935-019-0907-x. eCollection 2019.
Emerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood.
We performed a comprehensive meta-analysis to evaluate the biomarker performance of individual miR-29 and the related miRNA combination biomarkers. Meanwhile, we conducted an integrative bioinformatics analysis to unfold the underlying biological function of miR-29 and their relationship with CRC.
Using miR-29 expression to diagnose CRC produced 0.82 area under the curve, 70% sensitivity and 81% specificity while the combination biomarkers based on miR-29 enhanced the diagnostic power with an AUC of 0.86, a sensitivity of 78% and a specificity of 91%. For the prognosis evaluation, patients with higher expression of miR-29 had better survival outcome (pooled HR 0.78; 95% CI 0.56-1.07). In addition, miR-29 has also been identified as potential biomarker for predicting recurrence and metastasis in CRC. Then the genes regulated by the miR-29 family were retrieved and found closely associated with the molecular pathogenesis of CRC according to the gene ontology and pathway analysis. Furthermore, hub nodes and significant modules were identified from the protein-protein interaction network constructed with miR-29 family targets, which were also confirmed highly involved in the establishment and development of CRC.
Current evidences suggest miR-29 family may become promising biomarkers for risk, recurrence, metastasis and survival outcome of CRC. Meanwhile our data highlight the potential clinical use of miRNA combination biomarkers. Nevertheless, further prospective studies are warranted before the application of the useful biomarkers in the clinical.
新出现的证据表明，miR-29家族有望成为结直肠癌（CRC）的生物标志物，但其生物标志物潜力和分子机制仍知之甚少。
我们进行了一项全面的荟萃分析，以评估单个miR-29及相关miRNA组合生物标志物的生物标志物性能。同时，我们进行了综合生物信息学分析，以揭示miR-29的潜在生物学功能及其与CRC的关系。
使用miR-29表达诊断CRC时，曲线下面积为0.82，灵敏度为70%，特异性为81%，而基于miR-29的组合生物标志物提高了诊断能力，AUC为0.86，灵敏度为78%，特异性为91%。对于预后评估，miR-29表达较高的患者生存结果较好（合并风险比0.78；95%置信区间0.56 - 1.07）。此外，miR-29也被确定为预测CRC复发和转移的潜在生物标志物。然后检索了受miR-29家族调控的基因，根据基因本体论和通路分析发现它们与CRC的分子发病机制密切相关。此外，从用miR-29家族靶点构建的蛋白质-蛋白质相互作用网络中鉴定出枢纽节点和重要模块，它们也被证实高度参与CRC的发生和发展。
目前的证据表明，miR-29家族可能成为CRC风险、复发、转移和生存结果的有前景的生物标志物。同时，我们的数据突出了miRNA组合生物标志物的潜在临床应用价值。然而，在将这些有用的生物标志物应用于临床之前，仍需要进一步的前瞻性研究。
