Wang Shuangkuai, Tong Yuantao, Zong Hui, Xu Xuewen, Crabbe M James C, Wang Ying, Zhang Xiaoyan
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Department of Medicine Library, Tongji University Library, Tongji University, Shanghai 200092, China.
Genes (Basel). 2022 Feb 17;13(2):365. doi: 10.3390/genes13020365.
Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). However, there are still inconsistent standards of gene panels using next-generation sequencing and poor correlation between the TMB genes, immune cell infiltrating, and prognosis. We applied text-mining technology to construct specific TMB-associated gene panels cross various cancer types. As a case exploration, Pearson's correlation between TMB genes and immune cell infiltrating was further analyzed in colorectal cancer. We then performed LASSO Cox regression to construct a prognosis predictive model and calculated the risk score of each sample for receiver operating characteristic (ROC) analysis. The results showed that the assessment of TMB gene panels performed well with fewer than 500 genes, highly mutated genes, and the inclusion of synonymous mutations and immune regulatory and drug-target genes. Moreover, the analysis of TMB differentially expressed genes (DEGs) suggested that JAKMIP1 was strongly correlated with the gene expression level of CD8 T cell markers in colorectal cancer. Additionally, the prognosis predictive model based on 19 TMB DEGs reached AUCs of 0.836, 0.818, and 0.787 in 1-, 3-, and 5-year OS models, respectively (C-index: 0.810). In summary, the gene panel performed well and TMB DEGs showed great potential value in immune cell infiltration and in predicting survival.
肿瘤突变负荷（TMB）被认为是预测免疫检查点抑制剂（ICI）反应和疗效的潜在生物标志物。然而，使用下一代测序的基因panel标准仍不一致，且TMB基因、免疫细胞浸润与预后之间的相关性较差。我们应用文本挖掘技术构建了跨越多种癌症类型的特定TMB相关基因panel。作为一个案例探索，我们在结直肠癌中进一步分析了TMB基因与免疫细胞浸润之间的Pearson相关性。然后，我们进行LASSO Cox回归以构建预后预测模型，并计算每个样本的风险评分用于受试者工作特征（ROC）分析。结果表明，对TMB基因panel的评估在使用少于500个基因、高突变基因以及纳入同义突变和免疫调节及药物靶点基因时表现良好。此外，对TMB差异表达基因（DEG）的分析表明，JAKMIP1与结直肠癌中CD8 T细胞标志物的基因表达水平密切相关。此外，基于19个TMB DEG的预后预测模型在1年、3年和5年总生存期模型中的AUC分别达到0.836、0.818和0.787（C指数：0.810）。总之，该基因panel表现良好，TMB DEG在免疫细胞浸润和预测生存方面显示出巨大的潜在价值。
