Exploration of histone protein γ-H2AX as a prognostic factor in soft tissue sarcomas and its association with biological behavior, immune cell environment and survival in leiomyosarcoma

• Published in: International journal of cancer 2024-12
• Main Authors: Simon, Adrian Georg, Lyu, Su Ir, Schultheis, Anne Maria, Stahl, David, Wuerdemann, Nora, Walter, Sebastian, Hieggelke, Lena, Buettner, Reinhard, Bruns, Christiane Josephine, Eysel, Peer, Schiffmann, Lars Mortimer, Knipper, Karl, Mallmann, Peter, Quaas, Alexander, Ullrich, Roland
• Format: Article
• Language: English
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.35310

This study evaluates the H2AX/γ-H2AX expression in soft tissue sarcomas (STS), its implications for biological behavior and immune environment, and its potential as a prognostic biomarker. RNA-Seq data from 237 STS were obtained from The Cancer Genome Atlas project. Patients were stratified by H2AX mRNA expression using a survival-associated cutoff. Differentially expressed genes and pathways as well as immune signatures between H2AX - and H2AX tumors were identified with DESeq2 analysis, gene set enrichment analyses (GSEA), Enrichr pathway analysis and CIBERSORTx. Tissue microarrays of a different cohort of 291 STS were generated for immunohistochemical staining to assess γ-H2AX protein expression, followed by statistical evaluation. High H2AX mRNA expression was associated with shorter overall survival (OS) in STS (p = 0.02), particularly in leiomyosarcomas (LMS) (p