ArticleBMC cancer2021
The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Gastric carcinoma harbouring loss‑of‑function mutations in theOncology letters · 2025Article
- Investigation of tumor mutation burden using the comprehensive genomic profiling data of vulvar and vaginal malignant tumors: an observational study using C-CAT database.International journal of clinical oncology · 2025Observational
- ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma.Cancer letters · 2025Article
- Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies.Cell death & disease · 2025Review
- Epigenetic developmental mechanisms underlying sex differences in cancer.The Journal of clinical investigation · 2024Review
- Somatic mutational landscape reveals mutational signatures and significantly mutated genes of cancer immunotherapeutic outcome and sex disparities.Frontiers in immunology · 2024Article
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- Development and verification of a newly established cuproptosis-associated lncRNA model for predicting overall survival in uterine corpus endometrial carcinoma.Translational cancer research · 2023Article
- Multiomic sequencing of paired primary and metastatic small bowel carcinoids.F1000Research · 2023Article
- EBV and MSI Status in Gastric Cancer: Does It Matter?Cancers · 2022Article
- Sex disparities in DNA damage response pathways: Novel determinants in cancer formation and therapy.iScience · 2022Review
- Predicting Prognosis and Distinguishing Cold and Hot Tumors in Bladder Urothelial Carcinoma Based on Necroptosis-Associated lncRNAs.Frontiers in immunology · 2022Article
- Immune Checkpoint Blockade in Chinese Patients With Hepatocellular Carcinoma: Characteristics and Particularity.Frontiers in oncology · 2022Review
- Sex Disparity in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.Journal of oncology · 2022Review
- Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma.Frontiers in oncology · 2022Article
- Clinicopathological Significance of ATRX Expression in Nasopharyngeal Carcinoma Patients: A Retrospective Study.Journal of Cancer · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGenetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy.
methodsGenomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM).
resultsATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455-0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596-1.362, P = 0.712).
conclusionsATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.
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