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hsa-miR-130b-3p Predicts Poor Prognosis Across Renal Cell Carcinoma Subtypes via CD8+T Cell Depletion: A Multi-Omics and Clinical Validation StudyImmune Evasion

yang, w.; Dong, z.

2025-09-19 molecular biology
10.1101/2025.09.15.676345 bioRxiv
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Abstract BackgroundRenal cell carcinoma (RCC) is an aggressive genitourinary malignancy comprising three major subtypes: clear cell (KIRC), chromophobe (KICH), and papillary (KIRP). MicroRNAs (miRNAs) orchestrate renal cell carcinoma (RCC) progression, yet pan-subtype biomarkers remain elusive. MethodsHsa-miR-130b-3p was upregulated in all subtypes (log2FC=1.65,FDR=1.07x10- in GSE16441), correlating with poor OS (HR=1.56-2.38, p<0.05) and reduced CD8+ T cell infiltration (r=-0.32, p=0.01). Functional enrichment linked it to mTOR/HIF-1 signaling. ResultsHsa-miR-130b-3p was upregulated in all subtypes (log2FC=1.65, FDR=1.07x10- in GSE16441), correlating with poor OS (HR=1.56-2.38, p<0.05) and reduced CD8+ T cell infiltration (r=-0.32, p=0.01). Functional enrichment linked it to mTOR/HIF-1 signaling. Conclusionhsa-miR-130b-3p emerges as a simple yet powerful predictor of RCC progression and prognosis, warranting further clinical validation. As a pan-subtype biomarker (3-year AUC=0.82), hsa-miR-130b-3p may facilitate RCC immune evasion, warranting liquid biopsy validation. This study fills a gap in non-clear cell RCC (KICH/KIRP) by identifying hsa-miR-130b-3p as the first pan-subtype miRNA biomarker (3-year AUC=0.82, p<0.001), validated in 894 TCGA samples and 34 GSE16441 clinical cases. (See Figure 1 for the Graphical Abstract.) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/676345v1_fig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@18e8forg.highwire.dtl.DTLVardef@3668f5org.highwire.dtl.DTLVardef@24d6fdorg.highwire.dtl.DTLVardef@9eb696_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1C_FLOATNO Graphical Abstract C_FIG

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