Laboratory of Intracellular Signaling in Health and Disease, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, Russia, 119991.
Laboratory of Bioinformatics, Faculty of Computer Science, National Research University Higher School of Economics, Moscow, Russia.
Sci Rep. 2022 Aug 26;12(1):14588. doi: 10.1038/s41598-022-18620-y.
Clear cell renal carcinoma has been reported in many research studies as a rather heterogeneous disease. Identification of different subtypes and their molecular characteristics can help in choosing a more effective treatment and predicting a response to it. In this study, using multi-omics clustering of RNA-Seq data of patients with clear cell renal carcinoma from TCGA. Specific genes were identified for the most aggressive ccRCC subtype associated with metastasis and a subtype associated with a more favorable course of the disease. Among them were genes associated with blood clotting (FGA, FGG) and genes associated with changes in the immune characteristics of a tumor (ENAM, IGFBP1, IL6). In addition, an association of hub genes of poor survival ccRCC subtype with the levels of infiltration of endothelial cells, hematopoietic stem cells, T cells NK and mast cells was revealed. It was shown that MFI2, CP, FGA, and FGG expression can predict the response to sunitinib, while the APOB, ENAM, IGFBP1, and MFI2 expression predict the response to nivolumab. The results obtained provide insight into the genetic characteristics underlying the aggressive subtype of ccRCC and may help develop new approaches to the treatment of this disease.
透明细胞肾细胞癌在许多研究中被报道为一种相当异质性的疾病。鉴定不同的亚型及其分子特征有助于选择更有效的治疗方法，并预测其反应。在这项研究中，我们使用 TCGA 透明细胞肾细胞癌患者的 RNA-Seq 数据进行了多组学聚类。鉴定出与转移相关的侵袭性最强的 ccRCC 亚型和与疾病更有利病程相关的亚型的特定基因。其中包括与凝血（FGA、FGG）相关的基因和与肿瘤免疫特征变化相关的基因（ENAM、IGFBP1、IL6）。此外，还揭示了不良预后 ccRCC 亚型的枢纽基因与内皮细胞、造血干细胞、T 细胞 NK 和肥大细胞浸润水平之间的关联。结果表明，MFI2、CP、FGA 和 FGG 的表达可以预测舒尼替尼的反应，而 APOB、ENAM、IGFBP1 和 MFI2 的表达可以预测 nivolumab 的反应。所得结果深入了解了 ccRCC 侵袭性亚型的遗传特征，并可能有助于开发治疗这种疾病的新方法。
