免疫疗法
肿瘤科
内科学
肿瘤微环境
医学
微卫星不稳定性
佐剂
化疗
子群分析
癌症
生存分析
免疫系统
免疫学
生物
荟萃分析
等位基因
基因
生物化学
微卫星
作者
Daniel Skubleny,Kieran Purich,Donald R. McLean,Sebastião N. Martins-Filho,Klaus Buttenschoen,Erika Haase,Michael McCall,Sunita Ghosh,Jennifer L. Spratlin,Dan Schiller,Gina R. Rayat
标识
DOI:10.1158/1078-0432.ccr-23-3523
摘要
Abstract Purpose: We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG) and the Tumour Microenvironment Score (TME) to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations. Experimental Design: Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG and TME subtypes and applied to 2,202 gastric cancer patients from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model. A propensity score matched analysis was performed to evaluate the subgroup effect of adjuvant chemotherapy on molecular subtypes. A public external cohort comprised of metastatic gastric cancer treated with immunotherapy was used to externally validate the molecular subtypes. Results: Classification models for TCGA, ACRG and TME achieved an accuracy ± standard deviation of 89.5% ± 0.04, 84.7% ± 0.04 and 89.3% ± 0.02, respectively. We identified the TME score as the only significantly prognostic classification system (HR 0.54 [95% CI 0.39, 0.74], global Wald test p<0.001). In our subgroup analysis, patients who received adjuvant chemotherapy achieved greater survival with increasing TME score (HR 0.47 [95% CI 0.29, 0.74], interaction p<0.05). The combination of TME High and microsatellite instability (MSI) scores significantly outperformed MSI as a univariable predictor of immunotherapy response. Conclusions: We conclude that the Tumour Microenvironment Score is a predominate driver of prognosis as well as chemotherapy and immunotherapy-related outcomes in gastric cancer. This paper provides a foundation for additional analyses and translational work.
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