Wu Jun, Lou Yuqing, Ma Yi-Min, Xu Jun, Shi Tieliu
Center for Bioinformatics and Computational Biology, And the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Front Genet. 2021 Nov 12;12:741112. doi: 10.3389/fgene.2021.741112. eCollection 2021.
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with heterogeneous outcomes and diverse therapeutic responses. To classify patients into different groups and facilitate the suitable therapeutic strategy, we first selected eight microRNA (miRNA) signatures in The Cancer Genome Atlas (TCGA)-LUAD cohort based on multi-strategy combination, including differential expression analysis, regulatory relationship, univariate survival analysis, importance clustering, and multivariate combinations analysis. Using the eight miRNA signatures, we further built novel risk scores based on the predefined cutoff and beta coefficients and divided the patients into high-risk and low-risk groups with significantly different overall survival time (-value < 2 e-16). The risk-score model was confirmed with an independent dataset (-value = 4.71 e-4). We also observed that the risk scores of early-stage patients were significantly lower than those of late-stage patients. Moreover, our model can also provide new insights into the current clinical staging system and can be regarded as an alternative system for patient stratification. This model unified the variable value as the beta coefficient facilitating the integration of biomarkers obtained from different omics data.
肺腺癌（LUAD）是肺癌最常见的亚型，其预后异质性强，治疗反应多样。为了将患者分为不同组并制定合适的治疗策略，我们首先基于多策略组合，在癌症基因组图谱（TCGA）-LUAD队列中选择了八个微小RNA（miRNA）特征，包括差异表达分析、调控关系、单变量生存分析、重要性聚类和多变量组合分析。利用这八个miRNA特征，我们进一步基于预定义的截断值和β系数构建了新的风险评分，并将患者分为总生存时间显著不同的高风险组和低风险组（P值<2×10⁻¹⁶）。该风险评分模型在一个独立数据集上得到了验证（P值=4.71×10⁻⁴）。我们还观察到，早期患者的风险评分显著低于晚期患者。此外，我们的模型还可以为当前的临床分期系统提供新的见解，可被视为患者分层的替代系统。该模型将变量值统一为β系数，便于整合从不同组学数据中获得的生物标志物。
