Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Aging (Albany NY). 2020 Feb 6;12(3):2302-2332. doi: 10.18632/aging.102746.
Immune status affects the initiation and progression of clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma. In this study, we identified an immune-related, five-gene signature that improves survival prediction in ccRCC. Patients were classified as high- and low-risk based on the signature risk score. Survival analysis showed differential prognosis, while principal component analysis revealed distinctly different immune phenotypes between the two risk groups. High-risk patients tended to have advanced stage, higher grade disease, and poorer prognoses. Functional enrichment analysis showed that the signature genes were mainly involved in the cytokine-cytokine receptor interaction pathway. Moreover, we found that tumors from high-risk patients had higher relative abundance of T follicular helper cells, regulatory T cells, and M0 macrophages, and higher expression of PD-1, CTLA-4, LAG3, and CD47 than low-risk patients. This suggests our gene signature may not only serve as an indicator of tumor immune status, but may be a promising tool to select high-risk patients who may benefit from immune checkpoint inhibitor therapy. Multivariate Cox regression analysis showed that the signature remained an independent prognostic factor after adjusting for clinicopathological variables, while prognostic accuracy was further improved after integrating clinical parameters into the analysis.
免疫状态影响透明细胞肾细胞癌（ccRCC）的发生和进展，ccRCC 是肾细胞癌最常见的亚型。在本研究中，我们确定了一个与免疫相关的五基因特征，该特征可改善 ccRCC 的生存预测。根据特征风险评分，患者被分为高风险和低风险组。生存分析显示出不同的预后，而主成分分析显示出两组之间明显不同的免疫表型。高风险患者往往处于晚期、疾病分级较高且预后较差。功能富集分析表明，特征基因主要参与细胞因子-细胞因子受体相互作用途径。此外，我们发现高风险患者的肿瘤中滤泡辅助 T 细胞、调节性 T 细胞和 M0 巨噬细胞的相对丰度较高，PD-1、CTLA-4、LAG3 和 CD47 的表达水平也较高。这表明我们的基因特征不仅可以作为肿瘤免疫状态的指标，还可能是选择可能从免疫检查点抑制剂治疗中获益的高危患者的有前途的工具。多变量 Cox 回归分析表明，在调整临床病理变量后，该特征仍然是一个独立的预后因素，而在将临床参数纳入分析后，预后准确性进一步提高。
