ArticleBMC cancer2026
Integrated multi-omics analysis reveals folate metabolism-related genes as prognostic markers and therapeutic targets in clear cell renal cell carcinoma.
Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundClear cell renal cell carcinoma (ccRCC) is an aggressive tumor with high metastatic potential and therapeutic resistance, yet the role of folate metabolism in its pathogenesis and immune evasion remains unclear. This study aims to develop and validate a folate metabolism-related gene (FMRG) scoring system to stratify patients by prognostic risk and immune phenotypes, and to explore the functional role of key FMRGs in ccRCC progression.
methodsUsing transcriptomic and clinical data from The Cancer Genome Atlas (TCGA), we developed a folate metabolism-related gene (FMRG) scoring system via integrative machine learning and validated it in an external cohort. We analyzed associations of the FMRG score with clinicopathological features, biological pathways, immune infiltration, therapeutic responsiveness, and drug sensitivity. Single-cell RNA sequencing and spatial transcriptomics mapped candidate gene expression, and in vitro experiments validated the functional role of NGF.
resultsA ten-gene prognostic model based on the FMRG score stratified ccRCC patients into groups with distinct clinical outcomes, immune profiles, and therapeutic responses. NGF was upregulated in ccRCC, with heterogeneous spatial expression. Functional assays showed that NGF enhances proliferation, migration, and invasion.
conclusionsThis folate metabolism-based scoring framework facilitates prognostic stratification, tumor microenvironment characterization, and prediction of immunotherapy response in ccRCC. NGF is identified as a functional mediator of tumor progression, offering potential therapeutic targets and insights into metabolic-immune crosstalk.
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