Department of Urology, Suzhou Ninth People's Hospital, Soochow University, Suzhou 215000, China.
Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Huinan Town, Pudong, Shanghai 201399, China.
Aging (Albany NY). 2022 Sep 1;14(17):6917-6935. doi: 10.18632/aging.204252.
Accumulating pieces of evidence suggested that immunotypes may indicate the overall immune landscape in the tumor microenvironment, which were closely related to therapeutic response. The purpose of this study was to classify and define the immune subtypes of clear cell renal cell carcinoma (ccRCC), so as to authenticate the potential immune subtypes that respond to immunotherapy. Transcriptome expression profile and mutation profile data of ccRCC, as well as clinical characteristics used in this study were obtained from TCGA database. There were significant differences in the infiltration of immune cells, immune checkpoints, and antigens between ccRCC and para-cancerous tissues. According to immune components, patients with ccRCC were divided into three immune subtypes, with different clinical and molecular characteristics. Compared with other subtypes, IS2 showed cold immune phenotype, and was associated with better survival. IS1 represented complex immune populations and was associated with poor overall survival (OS) and progression free survival (PFS). Further analysis indicated that expression of immune checkpoints also differed among the three subtypes, and was abnormally up-regulated in IS3. Pathway enrichment analysis indicated that the mTOR signaling pathway was abnormally enriched in IS3, while the TGF_BETA, ANGIOGENESIS and receptor tyrosine kinase signaling pathways were abnormally enriched in IS2. Furthermore, there was an abnormal enrichment of the epithelial-to-mesenchymal transition (EMT) signaling pathway in IS1, which may be associated with a higher rate of metastasis. Finally, SCG2 was screened as a specific antigen of ccRCC, which was not only related to poor prognosis, but also significantly associated with immune cells and immune checkpoints. In conclusion, the immune subtypes of ccRCC may provide new insights into the tumor biology and the precise clinical management of this disease.
越来越多的证据表明，免疫表型可能反映肿瘤微环境中的整体免疫状态，与治疗反应密切相关。本研究旨在对透明细胞肾细胞癌（ccRCC）进行分类和定义免疫亚型，以鉴定对免疫治疗有反应的潜在免疫亚型。本研究从 TCGA 数据库中获取了 ccRCC 的转录组表达谱和突变谱数据以及临床特征。ccRCC 与癌旁组织之间的免疫细胞浸润、免疫检查点和抗原存在显著差异。根据免疫成分，将 ccRCC 患者分为三种免疫亚型，具有不同的临床和分子特征。与其他亚型相比，IS2 表现出冷免疫表型，与更好的生存相关。IS1 代表复杂的免疫群体，与较差的总生存期（OS）和无进展生存期（PFS）相关。进一步分析表明，三种亚型之间免疫检查点的表达也存在差异，IS3 中表达异常上调。通路富集分析表明，mTOR 信号通路在 IS3 中异常富集，而 TGF_BETA、血管生成和受体酪氨酸激酶信号通路在 IS2 中异常富集。此外，IS1 中上皮-间充质转化（EMT）信号通路异常富集，这可能与较高的转移率有关。最后，筛选出 SCG2 作为 ccRCC 的特异性抗原，不仅与不良预后相关，而且与免疫细胞和免疫检查点显著相关。总之，ccRCC 的免疫亚型可能为肿瘤生物学和该疾病的精确临床管理提供新的见解。
