Zeng Xing, Li Le, Hu Zhiquan, Peng Dan
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2022 Mar 30;12:832027. doi: 10.3389/fonc.2022.832027. eCollection 2022.
Despite the increasing importance and status of immune checkpoint blockade (ICB), little is known about the underlying molecular mechanisms determining the target clear cell renal cell carcinoma (ccRCC) population. In this study, we screened out 6 immune cells strongly correlated with expression levels of PD-L1 and IFN-γ based on the ccRCC samples extracted from GSE and TCGA data sets. By performing unsupervised clustering and lasso regression analysis, we grouped the ccRCC into 4 clusters and selected the two most distinct sub-clusters for further investigation-cluster A1 and B1. Next, we compared the two clusters in terms of mRNA, somatic mutations, copy number variations, DNA methylation, miRNA, lncRNA and constructed the differentially expressed genes (DEGs) hub by combing together the previous results at levels of DNA methylation, miRNA, and lncRNA. PTPRG and CHL1 were identified as key nodes in the regulation hub of immunophenotypes in ccRCC patients. Finally, we established the prognosis model by using Lasso-Cox regression and Kaplan-Meier analysis, recognizing WNT2, C17orf66, and PAEP as independent significant risk factors while IRF4 as an independent protective factor.
尽管免疫检查点阻断（ICB）的重要性和地位日益提高，但对于决定目标透明细胞肾细胞癌（ccRCC）群体的潜在分子机制却知之甚少。在本研究中，我们基于从GSE和TCGA数据集中提取的ccRCC样本，筛选出与PD-L1和IFN-γ表达水平密切相关的6种免疫细胞。通过进行无监督聚类和套索回归分析，我们将ccRCC分为4个簇，并选择两个最不同的子簇进行进一步研究——簇A1和B1。接下来，我们在mRNA、体细胞突变、拷贝数变异、DNA甲基化、miRNA、lncRNA方面比较了这两个簇，并通过整合先前在DNA甲基化、miRNA和lncRNA水平上的结果构建了差异表达基因（DEG）枢纽。PTPRG和CHL1被确定为ccRCC患者免疫表型调控枢纽中的关键节点。最后，我们通过套索-考克斯回归和卡普兰-迈耶分析建立了预后模型，确定WNT2、C17orf66和PAEP为独立的显著危险因素，而IRF4为独立的保护因素。
