Sahu Divya, Chang Yu-Lin, Lin Yin-Chen, Lin Chen-Ching
Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Int J Mol Sci. 2021 Apr 22;22(9):4384. doi: 10.3390/ijms22094384.
The genes influencing cancer patient mortality have been studied by survival analysis for many years. However, most studies utilized them only to support their findings associated with patient prognosis: their roles in carcinogenesis have not yet been revealed. Herein, we applied an in silico approach, integrating the Cox regression model with effect size estimated by the Monte Carlo algorithm, to screen survival-influential genes in more than 6000 tumor samples across 16 cancer types. We observed that the survival-influential genes had cancer-dependent properties. Moreover, the functional modules formed by the harmful genes were consistently associated with cell cycle in 12 out of the 16 cancer types and pan-cancer, showing that dysregulation of the cell cycle could harm patient prognosis in cancer. The functional modules formed by the protective genes are more diverse in cancers; the most prevalent functions are relevant for immune response, implying that patients with different cancer types might develop different mechanisms against carcinogenesis. We also identified a harmful set of 10 genes, with potential as prognostic biomarkers in pan-cancer. Briefly, our results demonstrated that the survival-influential genes could reveal underlying mechanisms in carcinogenesis and might provide clues for developing therapeutic targets for cancers.
多年来，通过生存分析对影响癌症患者死亡率的基因进行了研究。然而，大多数研究仅将它们用于支持与患者预后相关的研究结果：它们在致癌过程中的作用尚未揭示。在此，我们应用了一种计算机模拟方法，将Cox回归模型与蒙特卡罗算法估计的效应大小相结合，以筛选16种癌症类型中6000多个肿瘤样本中的生存影响基因。我们观察到，生存影响基因具有癌症依赖性特性。此外，有害基因形成的功能模块在16种癌症类型中的12种以及泛癌中始终与细胞周期相关，表明细胞周期失调可能损害癌症患者的预后。保护基因形成的功能模块在癌症中更为多样；最普遍的功能与免疫反应相关，这意味着不同癌症类型的患者可能会发展出不同的抗癌机制。我们还鉴定出一组10个有害基因，它们有可能作为泛癌的预后生物标志物。简而言之，我们的结果表明，生存影响基因可以揭示致癌的潜在机制，并可能为开发癌症治疗靶点提供线索。
