Evidence map›Paper›PMID 41403935›Full record

ArticleFrontiers in immunology2025

Integrative multi-omics analysis identifies a PTM-related immune signature and IRF9 as a driver in ccRCC.

Zixiang Li, Xun Li, Simeng Hu, Shan Jiang, Junqi Wang

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

5 authors.

Zixiang Li *Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Xun Li *Emergency Center of the Affiliated Hospital of Xuzhou Medical University , Xuzhou, China.
Simeng Hu *Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Shan JiangDepartment of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Junqi WangDepartment of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) exhibits marked heterogeneity and variable benefit from immune checkpoint inhibitors (ICIs). Post-translational modifications (PTMs) regulate immune signaling and tumor behavior, yet PTM-informed biomarkers for ccRCC remain underexplored. Methods: We intersected immune-related genes, PTM-related genes, and differentially expressed genes in TCGA-KIRC to derive candidates and built a prognostic model across TCGA and E-MTAB-1980 using multiple algorithms, selecting a random survival forest-based post-translational modification-related signature (PTMRS) with the best performance. Prognostic value and independence were evaluated by time-dependent ROC, Kaplan-Meier, and multivariate Cox analyses. Tumor immune context was profiled by immune infiltration scores, immune checkpoints, and TIDE to infer dysfunction/exclusion and ICI response. Genomic features (driver mutations, pathway alterations, tumor mutational burden) and an external ICI cohort (IMvigor210) were analyzed. Single-cell RNA-seq with CellChat, trajectory, and UCell assessed cell-cell communication and PTMRS distribution across immune subsets. Experimental validation included IHC and qPCR of IRF9, loss- and gain-of-function assays (Transwell, wound healing, CCK-8, colony, EdU), and molecular dynamics to explore IRF9 compound binding. Results: We established a five-gene PTMRS that robustly stratified prognosis in training, testing, and external cohorts and remained an independent predictor. High-PTMRS tumors displayed immunosuppressive features, including greater infiltration of Tregs/MDSCs/macrophages, higher expression of immunosuppressive checkpoints, and elevated TIDE scores with lower predicted ICI responsiveness. High PTMRS associated with alterations in oncogenic pathways and higher TMB. In IMvigor210, high PTMRS linked to inferior outcomes and non-response. Single-cell analyses showed PTMRS enrichment in Tregs and exhausted CD8 Conclusion: PTMRS is a PTM-informed immune signature that reflects an immunosuppressive tumor microenvironment, improves prognostic stratification, and indicates ICI benefit in ccRCC. Experimental data pinpoint IRF9 as a functional driver and potential therapeutic target within this PTM-immunity axis.

Indexed as

Biomarkers, TumorCarcinoma, Renal CellKidney NeoplasmsProtein Processing, Post-TranslationalFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsMaleMultiomicsPrognosisTumor MicroenvironmentBiomarkers, TumorImmune Checkpoint InhibitorsccRCCimmunotherapyIRF9post-translational modifications (PTMs)single-cell RNA sequencingtumor microenvironment

Identifiers

PMID41403935
PMCPMC12702869

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.