ArticleClinical and translational medicine2025
Titin gene mutations enhance radiotherapy efficacy via modulation of tumour immune microenvironment in rectum adenocarcinoma.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- Phase separation of MARCH1 promotes rectal adenocarcinoma progression through PHLPP2 ubiquitination.Translational cancer research · 2026Article
- Diverse genomic and transcriptomic heterogeneity in EGFR-mutant lung adenocarcinoma between exon 19 del and exon 21 L858R.Cell communication and signaling : CCS · 2026Article
- Single-cell RNA sequencing analysis revealed a potential association between ELK3 expression and the progression of multiple myeloma.Frontiers in immunology · 2026Article
- Single-cell and bulk RNA analysis identifies EMT-associated CAF signatures and prognostic model in lung adenocarcinoma.Discover oncology · 2025Article
- Liquid-liquid phase separation in gastric cancer: identifying novel biomarkers and therapeutic targets through gene signature analysis.Frontiers in immunology · 2025Article
- Titin gene mutations enhance radiotherapy efficacy via modulation of tumour immune microenvironment in rectum adenocarcinoma.Clinical and translational medicine · 2025Article
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Abstract
objectiveThis study investigates the impact of Titin (TTN) gene mutations on radiotherapy sensitivity in rectum adenocarcinoma (READ) by examining changes in the tumour immune microenvironment.
methodsData on gene expression and mutations in READ were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics analysis explored the correlation between TTN mutations and immune cell infiltration. In vitro, lentiviral vectors were used to assess TTN mutations' effects on ANKRD1 expression in two READ cell lines. ANKRD1 was overexpressed, and clonogenic assays evaluated radiotherapy sensitivity. Flow cytometry, immunofluorescence, and comet assays examined mutations' impact on cell cycle, apoptosis, and DNA damage response (DDR). An in vivo mouse model and formalin-fixed paraffin-embedded samples from locally advanced rectal cancer (LARC) patients before and after radiotherapy were analyzed, followed by prognostic evaluation.
resultsBioinformatics revealed that TTN mutations increase radiation sensitivity in LARC by slowing cell proliferation, promoting apoptosis, and reducing DDR. TTN mutations also inhibit ANKRD1 expression via JUN disruption and enhance CD4/CD8 T-cell infiltration, improving anti-tumour immunity and outcomes. Observations from the clinical study showed a substantial decline in ANKRD1 expression levels alongside a notable surge in the counts of CD4
conclusionOur findings reveal that TTN mutations can serve as biomarkers for enhanced radiotherapy sensitivity in READ. By altering the tumour's immune microenvironment, these mutations may provide a novel target for personalized radiotherapy strategies, potentially improving therapeutic outcomes in patients with READ. HIGHLIGHTS: The association between TTN mutations and tumour mutation burden, as well as immune cell infiltration in READ, is examined. TTN mutations enhance the radiation sensitivity of READ cells and weaken DNA damage repair in response to radiation. TTN mutations increase the radiation sensitivity of READ cells by inhibiting ANKRD1. The infiltration of CD8
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