In Frontiers in immunology ; h5-index 100.0
BACKGROUND : Alterations in lipid metabolism promote tumor progression. However, the role of lipid metabolism in the occurrence and development of gastric cancer have not been fully clarified.
METHOD : Here, genes that are related to fatty acid metabolism and differentially-expressed between normal and gastric cancer tissues were identified in the TCGA-STAD cohort. The intersection of identified differentially-expressed genes with Geneset was determined to obtain 78 fatty acid metabolism-related genes. The ConsensusClusterPlus R package was used to perform differentially-expressed genes, which yielded divided two gastric cancer subtypes termed cluster 1 and cluster 2.
RESULTS : Patients in cluster 2 was found to display poorer prognosis than patients in cluster 1. Using machine learning method to select 8 differentially expressed genes among subtypes to construct fatty acid prognostic risk score model (FARS), which was found to display good prognostic efficacy. We also identified that certain anticancer drugs, such as bortezomib, elesclomol, GW843682X, and nilotinib, showed significant sensitivity in the high FARS score group. RGS2 was selected as the core gene upon an analysis of the gastric cancer single-cell, and Western blotting and immunofluorescence staining results revealed high level of expression of this gene in gastric cancer cells. The results of immunohistochemical staining showed that a large amount of RGS2 was deposited in the stroma in gastric cancer. A pan-cancer analysis also revealed a significant association of RGS2 with TMB, TIDE, and CD8+ T-cell infiltration in other cancer types as well. RGS2 may thus be studied further as a new target for immunotherapy in future studies on gastric cancer.
CONCLUSION : In summary, the FARS model developed here enhances our understanding of lipid metabolism in the TME in gastric cancer, and provides a theoretical basis for predicting tumor prognosis and clinical treatment.
Yang Shifeng, Sun Boshi, Li Wenjing, Yang Hao, Li Nana, Zhang Xinyu
2022
fatty acid, gastric cancer, immunotherapy, machine learning, tumor microenvironment
