Department of colorectal Surgery, Tianjin Union Medical Center, Tianjin, P.R. China.
Tianjin Institute of Coloproctology, Tianjin, P.R. China.
PLoS One. 2021 Oct 26;16(10):e0258741. doi: 10.1371/journal.pone.0258741. eCollection 2021.
To develop an autophagy-gene-based signature that could help to anticipate the therapeutic effects of Colorectal Cancer (CRC).
We downloaded the gene expression profiles of CRC samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Genes with significant prognostic value in CRC were screened through univariate Cox regression analysis, while the LASSO Cox regression method was applied to screen optimal genes to construct the autophagy-related prognostic signature.
11 autophagy genes were identified and selected for the establishment of prognosis prediction model for CRC patients. The CRC patients were classified into the low- and high-risk groups according to the optimal cutoff value. The time-dependent ROC curves indicated the good performance of this model in prognosis prediction, with AUC values of 0.66, 0.66, and 0.67 at 1, 3 and 5 years for TCGA samples, as well as AUC values of 0.63, 0.65 and 0.64 for GEO samples, respectively. The multivariate Cox regression analysis results confirmed risk score as the independent marker for prognosis prediction in CRC. Besides, the constructed nomogram also had high predictive value. The results analysis on the tumor infiltrating immune cells (TIICs) relative ratios and mRNA levels of key immune checkpoint receptors indicated the signature was closely related to immune microenvironment of CRC in the context of TIICs and immune checkpoint receptors' mRNA level. The proportion of MSI-L + MSI-H in the high-risk group was higher than that in the low-risk group. Moreover, the tumor purity was evaluated by estimate function package suggested that lower tumor purity in CRC might lead to a poorer prognosis.
The autophagy-related features obtained in this study were able to divide the CRC patients into low- and high-risk groups, which should be contribute to the decision-making of CRC treatment.
开发一个基于自噬基因的标志,以帮助预测结直肠癌(CRC)的治疗效果。
我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集下载了 CRC 样本的基因表达谱。通过单变量 Cox 回归分析筛选具有显著预后价值的基因,然后应用 LASSO Cox 回归方法筛选最佳基因构建自噬相关预后标志。
鉴定并选择了 11 个自噬基因,用于建立 CRC 患者的预后预测模型。根据最佳截断值,将 CRC 患者分为低风险组和高风险组。时间依赖性 ROC 曲线表明该模型在预后预测中具有良好的性能,TCGA 样本的 AUC 值分别为 0.66、0.66 和 0.67,在 1、3 和 5 年时,GEO 样本的 AUC 值分别为 0.63、0.65 和 0.64。多变量 Cox 回归分析结果证实风险评分是 CRC 预后预测的独立标志物。此外,构建的列线图也具有较高的预测价值。对肿瘤浸润免疫细胞(TIICs)相对比例和关键免疫检查点受体的 mRNA 水平进行分析的结果表明,该标志与 TIICs 和免疫检查点受体 mRNA 水平相关的 CRC 免疫微环境密切相关。高风险组中 MSI-L+MSI-H 的比例高于低风险组。此外,通过 estimate function 包评估肿瘤纯度表明,CRC 中的肿瘤纯度较低可能导致预后较差。
本研究获得的自噬相关特征能够将 CRC 患者分为低风险组和高风险组,有助于 CRC 治疗决策的制定。