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pmid:37795453
Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma.
Xiangsheng Li · Guangsheng Du · Liqi Li · Ke Peng
Frontiers in oncology · 2023 doi:10.3389/fonc.2023.1253783
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The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC.\nMethods: GSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients' clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation.\nResults: The variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy.\nConclusions: At the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. 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