Seven Fatty Acid Metabolism-Related Genes as Potential Biomarkers for Predicting the Prognosis and Immunotherapy Responses in Patients with Esophageal Cancer

Abstract

Background: Esophageal cancer (ESCA) is a major cause of cancer-related mortality worldwide. Altered fatty acid metabolism is a hallmark of cancer. However, studies on the roles of fatty acid metabolism-related genes (FRGs) in ESCA remain limited. Method: We identified differentially expressed FRGs (DE-FRGs). Then, the DE-FRGs prognostic model was constructed and validated using a comprehensive analysis. Moreover, the correlation between the risk model and clinical characteristics was investigated. A nomogram for predicting survival was established and evaluated. Subsequently, the difference in tumor microenvironment (TME) was compared between two risk groups. The sensitivity of key DE-FRGs to chemotherapeutic interventions and their correlation with immune cells were investigated. Finally, DEGs between two risk groups were measured and the prognostic value of key DE-FRGs in ESCA was confirmed in other databases. Results: A prognostic model was constructed based on seven selected DEG-FRGs. TNM staging and CD8+ T cells were significantly correlated with high-risk groups. Low-risk groups exhibited more infiltrated M0 macrophages, an activation of type II interferon (IFN-γ) responses, and were found to be more suitable for immunotherapy. Seven key DE-FRGs with prognostic value were found to be considerably influenced by different chemotherapy drugs. Conclusion: A prognostic model based on seven DE-FRGs may efficiently predict patient prognosis and immunotherapy response, helping to develop individualized treatment strategies in ESCA.

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

“…This cluster has three cluster-specific genes, GOLT1A, RAB27B and SLC28A3. GOLT1A has been reported to be differentially expressed between high and low risk groups for esophageal cancer [ 50 ] and RAB27B is a significant prognostic marker for metastasis and poor prognosis in colorectal cancer [ 51 – 53 ]. The TF that appears in the models of all three hit genes is GATA-binding factor 2 (GATA2).…”

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

“…In addition, lncRNAs such as LINC01068, TMEM92-AS1 and AC243967.2 have been reported to be correlated with iron metabolism and iron death, and be closely related to the infiltration of immune cells in ESCC[ 133 ]. Moreover, Zhang et al [ 134 ] reported that mitochondrial energy metabolism is associated with the TIME and poor prognosis in ESCC patients, and identified several fatty acid metabolism-related genes that are predictors of EC prognosis[ 135 ]. Additionally, tryptophan-derived metabolites have been shown to contribute to tumor immune escape, and been identified as biomarkers for EC metastasis and prognosis[ 136 ].…”