Zhao Bochao, Wang Weiqiang, Ye Haikun, Wang Jingchao, Meng Kewei, Yang Tao
Department of Gastrointestinal Surgery, Tianjin First Central Hospital, Tianjin, China.
Chem Biol Drug Des. 2023 Nov;102(5):1024-1033. doi: 10.1111/cbdd.14301. Epub 2023 Aug 2.
It is great significance of identifying valuable biomarkers for early diagnosis and prognostic prediction of colorectal cancer (CRC) patients. This study aimed at developing and validating a miRNAs-based signature as prognostic tool for CRC patients. The miRNA expression profile of 624 CRC samples (613 tumor tissues and 11 normal tissues) was analyzed, and 523 differentially expressed miRNAs (DEmiRNAs) were identified, in which 191 were downregulated and 332 were upregulated. All patients were randomly divided into a training cohort (N = 308) and an internal validation cohort (N = 200). Using the least absolute shrinkage and selection operator (LASSO) and Cox regression model, a prognostic signature of 10 miRNAs (hsa-miR-149-5p, hsa-miR-193b-5p, hsa-miR-193a-3p, hsa-miR-3677-3p, hsa-miR-29a-3p, hsa-miR-200c-5p, hsa-miR-200a-5p, hsa-miR-6854-5p, hsa-miR-216a-5p and hsa-miR-891a-5p) was developed in the training cohort. The risk score was calculated by the product of the expression level and the coefficients of each miRNA. The prognostic value of 10 miRNAs-based signature for CRC patients was tested and validated. Survival analysis indicated that high-risk patients (> 1.10) had a worse overall survival (OS) than low-risk (≤ 1.10) patients (5-year OS rate for training cohort: 59.3% vs. 78.9%, p < .001; validation cohort: 48.3% vs. 69.3%, p = .011). The miRNA-based signature was an independent prognostic factor for CRC patients (HR for training cohort:2.476, 95% CI:1.202-5.098, p = .014; HR for validation cohort:2.050, 95% CI:1.087-3.869, p = .027). The AUC values for 3-year and 5-year OS prediction were 0.718 and 0.784 in the training cohort, 0.659 and 0.614 in the validation cohort, respectively. The 10 miRNAs-based signature provided a proper prognostic stratification for CRC patients, and it might be a promising tool for survival prediction.
识别有价值的生物标志物对于结直肠癌（CRC）患者的早期诊断和预后预测具有重要意义。本研究旨在开发并验证一种基于miRNAs的特征作为CRC患者的预后工具。分析了624例CRC样本（613例肿瘤组织和11例正常组织）的miRNA表达谱，鉴定出523个差异表达的miRNA（DEmiRNAs），其中191个下调，332个上调。所有患者被随机分为训练队列（N = 308）和内部验证队列（N = 200）。使用最小绝对收缩和选择算子（LASSO）和Cox回归模型，在训练队列中开发了一个由10个miRNA组成的预后特征（hsa-miR-149-5p、hsa-miR-193b-5p、hsa-miR-193a-3p、hsa-miR-3677-3p、hsa-miR-29a-3p、hsa-miR-200c-5p、hsa-miR-200a-5p、hsa-miR-6854-5p、hsa-miR-216a-5p和hsa-miR-891a-5p）。风险评分通过每个miRNA的表达水平与系数的乘积来计算。对基于10个miRNA的特征对CRC患者的预后价值进行了测试和验证。生存分析表明，高危患者（>1.10）的总生存期（OS）比低危患者（≤1.10）更差（训练队列的5年OS率：59.3%对78.9%，p<0.001；验证队列：48.3%对69.3%，p = 0.011）。基于miRNA的特征是CRC患者的独立预后因素（训练队列的HR：2.476，95%CI：1.202 - 5.098，p = 0.014；验证队列的HR：2.050，95%CI：1.087 - 3.869，p = 0.027）。训练队列中3年和5年OS预测的AUC值分别为0.718和0.784，验证队列中分别为0.659和0.614。基于10个miRNA的特征为CRC患者提供了合适的预后分层，可能是一种有前景的生存预测工具。
