BACKGROUND Stomach adenocarcinoma(STAD)is a leading cause of cancer deaths,but its molecular and prognostic characteristics has never been fully illustrated.AIM To describe a molecular evaluation of primary STAD and d...BACKGROUND Stomach adenocarcinoma(STAD)is a leading cause of cancer deaths,but its molecular and prognostic characteristics has never been fully illustrated.AIM To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures.METHODS We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene(EMRG)expression profiles.RESULTS On the basis of 86 EMRGs that were significantly associated to patients’progression-free survival(PFS),we propose a molecular classification dividing gastric cancer into two subtypes:Cluster 1,most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority;and Cluster 2,which show early stages and better PFS.Moreover,we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process.Compared with patients with low-risk score,patients with high-risk score had shorter overall survival.Furthermore,calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature,and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures.According to gene set enrichment analysis,gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.CONCLUSION Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.展开更多
基金the National Natural Science Foundation of China,No.81972249,No.81802367,No.81802361 and No.82172702the Shanghai Clinical Research Plan of SHDC,No.SHDC2020CR4068+3 种基金the Shanghai Clinical Science and Technology Innovation Project of Municipal Hospital,No.SHDC12020102the Shanghai Science and Technology Development Fund,No.18ZR1408000,No.21ZR1414900 and No.19MC1911000the Clinical Research Project of Shanghai Municipal Health Committee,No.20194Y0348and the Shanghai“Rising Stars of Medical Talents”Youth Development Program Youth Medical Talents–Specialist Program,No.SHWSRS(2020)_087.
文摘BACKGROUND Stomach adenocarcinoma(STAD)is a leading cause of cancer deaths,but its molecular and prognostic characteristics has never been fully illustrated.AIM To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures.METHODS We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene(EMRG)expression profiles.RESULTS On the basis of 86 EMRGs that were significantly associated to patients’progression-free survival(PFS),we propose a molecular classification dividing gastric cancer into two subtypes:Cluster 1,most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority;and Cluster 2,which show early stages and better PFS.Moreover,we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process.Compared with patients with low-risk score,patients with high-risk score had shorter overall survival.Furthermore,calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature,and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures.According to gene set enrichment analysis,gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.CONCLUSION Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.
