Department of Human Resources, Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Department of Human Resources, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan.
Medicine (Baltimore). 2021 Mar 19;100(11):e24949. doi: 10.1097/MD.0000000000024949.
Currently, no effective prognostic model of clear cell renal cell carcinoma (ccRCC) based on immune cell infiltration has been developed. Recent studies have identified 6 immune groups (IS) in 33 solid tumors. We aimed to characterize the expression pattern of IS in ccRCC and evaluate the potential in predicting patient prognosis. The clinical information, immune subgroup, somatic mutation, copy number variation, and methylation score of patients with TCGA ccRCC cohort were downloaded from UCSC Xena for further analysis. The most dominant IS in ccRCC was the inflammatory subgroup (immune C3) (86.5%), regardless of different pathological stages, pathological grades, and genders. In the C3 subgroup, stage IV (69.1%) and grade 4 (69.9%) were the least presented. Survival analysis showed that the IS could effectively predict the overall survival (OS) (P < .0001) and disease-specific survival (DSS) (P < .0001) of ccRCC alone, of which group C3 (OS, HR = 2.3, P < .001; DSS, HR = 2.84, P < .001) exhibited the best prognosis. Among the most frequently mutated ccRCC genes, only VHL and PBRM1 were found to be common in the C3 group. The homologous recombination deficiency score was also lower. High heterogeneity was observed in immune cells and immunoregulatory genes of IS. Notably, CD4+ memory resting T cells were highly infiltrating, regulatory T cells (Treg) showed low infiltration, and most immunoregulatory genes (such as CX3CL1, IFNA2, TLR4, SELP, HMGB1, and TNFRSF14) were highly expressed in the C3 subgroup than in other subgroups. Enrichment analysis showed that adipogenesis, apical junction, hypoxia, IL2 STAT5 signaling, TGF-beta signaling, and UV response DN were activated, whereas E2F targets, G2M checkpoint, and MYC targets V2 were downregulated in the C3 group. Immune classification can more accurately classify ccRCC patients and predict OS and DSS. Thus, IS-based classification may be a valuable tool that enables individualized treatment of patients with ccRCC.
目前，尚未基于免疫细胞浸润开发出用于透明细胞肾细胞癌 (ccRCC) 的有效预后模型。最近的研究在 33 种实体瘤中鉴定出 6 种免疫群 (IS)。我们旨在描述 ccRCC 中 IS 的表达模式，并评估其预测患者预后的潜力。从 UCSC Xena 下载 TCGA ccRCC 队列患者的临床信息、免疫亚群、体细胞突变、拷贝数变异和甲基化评分，以进行进一步分析。ccRCC 中最主要的 IS 是炎症亚群 (免疫 C3) (86.5%)，无论病理阶段、病理分级和性别如何。在 C3 亚群中，IV 期 (69.1%)和 4 级 (69.9%)的比例最低。生存分析表明，IS 可有效预测 ccRCC 患者的总生存期 (OS) (P<0.0001) 和疾病特异性生存期 (DSS) (P<0.0001)，其中 C3 组 (OS，HR=2.3，P<0.001；DSS，HR=2.84，P<0.001) 表现出最佳预后。在最常突变的 ccRCC 基因中，仅 VHL 和 PBRM1 被发现存在于 C3 组中。同源重组缺陷评分也较低。IS 中的免疫细胞和免疫调节基因存在高度异质性。值得注意的是，CD4+记忆静止 T 细胞高度浸润，调节性 T 细胞 (Treg) 浸润程度较低，大多数免疫调节基因 (如 CX3CL1、IFNA2、TLR4、SELP、HMGB1 和 TNFRSF14) 在 C3 亚群中的表达高于其他亚群。富集分析表明，脂肪生成、顶端连接、缺氧、IL2 STAT5 信号、TGF-β信号和 UV 反应 DN 被激活，而 C3 组中 E2F 靶点、G2M 检查点和 MYC 靶点 V2 下调。免疫分类可以更准确地对 ccRCC 患者进行分类，并预测 OS 和 DSS。因此，基于 IS 的分类可能是一种有价值的工具，可实现 ccRCC 患者的个体化治疗。
