Abstract 5750: Quantification of histone methylation regulator-associated modification patterns was a potential biomarker for prognosis and associated with immunotherapy in gastric cancer

Abstract Background: Histone methylation (HM) is an abundant form of histone modification and recent studies have highlighted it strongly related to tumorigenicity and progression. However, histone methylation modification patterns and potential roles in gastric cancer have not been systematically elucidated. Method: In this study, we curated 53 histone methyltransferase regulators and 9 histone demethylase regulators. Identified histone methylation(HM)modification clusters based on the expression of 62 HM regulators. Principal component analysis (PCA) served to construct histone methylation score (HMScore) base on differential genes among three HM clusters. Evaluating the relationship between HMScore and clinical prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration and immunotherapy. Results: We identified distinct three HM modification clusters in patients with gastric cancer based on the expression of 62 HM regulators, which were association with different clinical prognosis, biological pathways and tumor microenvironment characterization. Based on HMScore to quantitatively evaluate the histone methylation modification patterns in gastric cancer patients. We founded that patients with a low-HMScore group(score<2.276) was association with poor prognosis. In addition, high-HMScore group(score≥2.276) displayed tumor mutation burden-high (TMB-H) and microsatellite instability-high (MSI-H), and correlation analysis indicated that HMScore was positively correlated with tumor mutation burden. Immune infiltration correlation analysis showed that HMScore strongly negative related to MDSC cell, mast cell and regulatory T cell. Survival analysis indicated that patients with TMB-H and high-HMScore were related to long clinical prognosis in gastric cancer. Moreover, patients with high-HMScore group had high abundance of PD-L1, and high-HMScore was confirmed sensitive response to immunotherapy in gastric cancer. Conclusion: This study provided a new model to evaluate individual gastric cancer histone methylation modification patterns. HMScore was benefit to evaluate clinical prognosis value and guide strategies to improve treatment in gastric cancer. Citation Format: Jiapeng Kang, Lu Yang, Jialin Lin, Dan Zhou, Canbin Fang, Feng Ye, Weiwei Tang. Quantification of histone methylation regulator-associated modification patterns was a potential biomarker for prognosis and associated with immunotherapy in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5750.