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Updated: Jul 30, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Comprehensive transcriptomic analyses identify KDM genes-related subtypes with different TME infiltrates in gastric
Haichao Zhang1, Haoran Wang2, Li Ye3
1Department of Osteoporosis and Bone Disease, Research Section of Geriatric Metabolic Bone Disease, Huadong Hospital Affiliated to Fudan University, Shanghai Geriatric Institute, Shanghai, 200032, China.
Abstract:
Histone lysine demethylases (KDMs) have been reported in various malignances, which affect transcriptional regulation of tumor suppressor or oncogenes. However, the relationship between KDMs and formation of tumor microenvironment (TME) in gastric cancer (GC) remain unclear and need to be comprehensively analyzed.In the present study, 24 KDMs were obtained and consensus molecular subtyping was performed using the "NMF" method to stratify TCGA-STAD into three clusters. The ssGSEA and CIBERSORT algorithms were employed to assess the relative infiltration levels of various cell types in the TME. The KDM_score was devised to predict patient survival outcomes and responses to both immunotherapy and chemotherapy.Three KDM genes-related molecular subtypes were Figured out in GC with distinctive clinicopathological and prognostic features. Based on the robust KDM genes-related risk_score and nomogram, established in our work, GC patients' clinical outcome can be well predicted. Furthermore, low KDM genes-related risk_score exhibited the more effective response to immunotherapy and chemotherapy.This study characterized three KDM genes-related TME pattern with unique immune infiltration and prognosis by comprehensively analyses of transcriptomic profiling. Risk_score was also built to help clinicians decide personalized anticancer treatment for GC patients, including in prediction of immunotherapy and chemotherapy response for patients.
Insights
Histone lysine demethylases (KDMs) influence tumor microenvironment (TME) in gastric cancer (GC). A new KDM-based risk score predicts patient outcomes and response to immunotherapy and chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Histone lysine demethylases (KDMs) play roles in various cancers by regulating gene transcription.
- The specific involvement of KDMs in the gastric cancer (GC) tumor microenvironment (TME) formation is not well understood.
Purpose of the Study:
- To comprehensively analyze the relationship between KDMs and TME in gastric cancer.
- To develop a predictive model for patient prognosis and treatment response based on KDM expression.
Main Methods:
- Utilized transcriptomic data from TCGA-STAD for analysis of 24 KDMs.
- Applied Non-negative Matrix Factorization (NMF) for molecular subtyping.
- Employed ssGSEA and CIBERSORT for TME immune cell infiltration assessment.
- Developed a KDM-based risk score (KDM_score) for outcome prediction.
Main Results:
- Identified three distinct KDM-related molecular subtypes in GC with unique clinicopathological and prognostic features.
- Established a robust KDM-related risk score and nomogram for predicting GC patient outcomes.
- Demonstrated that a lower KDM-related risk score correlates with better response to immunotherapy and chemotherapy.
Conclusions:
- Characterized three KDM-related TME patterns in GC, each associated with distinct immune infiltration and prognosis.
- The developed risk score aids clinicians in predicting patient outcomes and personalizing anticancer treatment strategies, including immunotherapy and chemotherapy.
- Highlights the potential of KDMs as therapeutic targets and biomarkers in gastric cancer.
