Key laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, China.
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
EBioMedicine. 2018 Sep;35:189-197. doi: 10.1016/j.ebiom.2018.08.042. Epub 2018 Aug 27.
Approximately 60% of patients with colorectal cancer (CRC) undergo either local recurrence or distant metastases after surgery. Current prognostic biomarkers are insufficient to predict recurrence of CRC and provide little forecast information about what patients are likely to receive benefit from the adjuvant chemotherapy. As microRNAs (miRNAs) constantly exist in human serum and being used to predict the prognosis of a various cancers, this study was designed to identify miRNA-based circulating biomarkers to predict clinical outcomes of CRC.
A serum-focused miRNA expression was used to investigate if miRNA expression profiles could predict the clinical outcomes of patients with CRC. We created miRNA signature profiles associated in the training set (n = 40), and further validated its prediction in two independent testing cohorts.
Using Cox regression and risk-score analysis, we identified a four-miRNA signature (miR-652-3p, miR-342-3p, miR-501-3p and miR-328-3p) for the prediction of tumor relapse and the overall survival(OS) of patients with CRC in the training set (n = 40). This miRNA signature was further validated in a testing set (n = 226) and another independent cohort (n = 56). A high-risk signature score was significantly associated with CRC tumor recurrence and poor treatment outcome. Multivariable Cox regression models indicated that the risk score, based on the four-miRNA signature, was an independent prognostic classifier for patients with CRC.
The serum miRNA signature may serve as a minimally invasive predictor for tumor relapse and treatment outcome in patients with CRC and provide a useful reference for treatment selection.
约 60%的结直肠癌（CRC）患者在手术后会出现局部复发或远处转移。目前的预后生物标志物不足以预测 CRC 的复发，并为患者可能从辅助化疗中获益提供很少的预测信息。由于 microRNAs（miRNAs）在人类血清中持续存在，并被用于预测各种癌症的预后，因此本研究旨在确定基于 miRNA 的循环生物标志物，以预测 CRC 的临床结果。
使用血清聚焦 miRNA 表达来研究 miRNA 表达谱是否可以预测 CRC 患者的临床结局。我们在训练集中创建了与 miRNA 特征相关的签名谱（n=40），并进一步在两个独立的测试队列中验证了其预测。
使用 Cox 回归和风险评分分析，我们在训练集中（n=40）确定了一个由四个 miRNA 组成的特征（miR-652-3p、miR-342-3p、miR-501-3p 和 miR-328-3p），用于预测 CRC 患者的肿瘤复发和总体生存（OS）。该 miRNA 特征在测试集（n=226）和另一个独立队列（n=56）中得到了进一步验证。高风险特征评分与 CRC 肿瘤复发和不良治疗结局显著相关。多变量 Cox 回归模型表明，基于四个 miRNA 特征的风险评分是 CRC 患者独立的预后分类器。
血清 miRNA 特征可作为 CRC 患者肿瘤复发和治疗结局的微创预测指标，并为治疗选择提供有用的参考。
