Redox Metabolism-Associated Molecular Classification of Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Redox metabolism has been recognized as the hallmark of cancer. But the concrete role of redox-related genes in patient stratification of ccRCC remains unknown. Herein, we aimed to characterize the molecular features of ccRCC based on the redox gene expression profiles from The Cancer Genome Atlas. Differentially expressed redox genes (DERGs) and vital genes in metabolism regulation were identified and analyzed in the ccRCC. Consensus clustering was performed to divide patients into three clusters (C1, C2, and C3) based on 139 redox genes with median FPKM value > 1 . We analyzed the correlation of clusters with clinicopathological characteristics, immune infiltration, gene mutation, and response to immunotherapy. Subclass C1 was metabolic active with moderate prognosis and associated with glucose, lipid, and protein metabolism. C2 had intermediate metabolic activity with worse prognosis and correlated with more tumor mutation burden, neoantigen, and aneuploidy, indicating possible drug sensitivities towards immune checkpoint inhibitors. Metabolic exhausted subtype C3 showed high cytolytic activity score, suggesting better prognosis than C1 and C2. Moreover, the qRT-PCR was performed to verify the expression of downregulated DERGs including ALDH6A1, ALDH1L1, GLRX5, ALDH1A3, and GSTM3, and upregulated SHMT1 in ccRCC. Overall, our study provides an insight into the characteristics of molecular classification of ccRCC patients based on redox genes, thereby deepening the understanding of heterogeneity of ccRCC and allowing prediction of prognosis of ccRCC patients.

Characterisation of spontaneous proximal tubule formation in vitro and development of a metastatic clear cell renal cell carcinoma (ccRCC) model

“…It can relay signals and activate MAPK, necessary for cell development, growth, survival, and differentiation [298]. Interestingly, our study found that KRAS is downregulated, and another study also concluded the same (Figure 3.27 c) [299].…”

Integrated analysis revealing a novel stemness-metabolism-related gene signature for predicting prognosis and immunotherapy response in hepatocellular carcinoma

“…Metabolic signatures play a crucial role in tumor subclassification and immunotherapy response prediction. Some previous research had confirmed that metabolic signatures showed good power in tumor sub-phenotype and treatment response prediction in diffuse large B-cell lymphoma ( 61 ), ovarian ( 62 ) and colorectal cancers ( 63 ) as well as clear cell renal cell carcinoma ( 64 ). Chen et al.…”

The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer

“…Meanwhile, another study has shown that hypo-expression of ALDH6A1 was associated with survival of metastatic prostate cancer patients [ 31 ]. The downregulated ALDH6A1 has been proved to regulate the immune response in clear cell renal cell carcinoma, which implied a new biomarker for the clinical immunotherapy of ccRCC patients [ 32 ]. Our study is for the first time to figure out the drug-metabolism related gene ALDH6A1 expression was low in gastric cancer group.…”