Pan-Cancer Analysis and Experimental Validation Identify ACOT7 as a Novel Oncogene and Potential Therapeutic Target in Lung Adenocarcinoma

SIMPLE SUMMARY: Acyl-CoA thioesterase 7 (ACOT7) is important in regulating cell cycle, cell proliferation, and glucose metabolism. Research on the functions of ACOT7 are seldom, and comprehensive pan-cancer analysis is lacking. We aimed to perform a pan-can analysis and validated the prognostic value of ACOT7 in lung adenocarcinoma. ACOT7 was tightly associated with the tumor microenvironment. The downregulation of ACOT7 expression suppressed cell proliferation and the migration of the PC9 cell line. ACOT7 is a novel oncogene and therapeutic target for lung adenocarcinoma. ABSTRACT: Background: Acyl-CoA thioesterase 7 (ACOT7) is of great significance in regulating cell cycle, cell proliferation, and glucose metabolism. The function of ACOT7 in pan-cancer and its capacity as a prognostic indicator in lung adenocarcinoma (LUAD) remains unknown. We intended to perform a comprehensive pan-cancer analysis of ACOT7 and to validate its value in LUAD. Methods: The expression levels, prognostic significance, molecular function, signaling pathways, and immune infiltration pattern of ACOT7 in 33 cancers were explored via systematic bioinformatics analysis. Multivariate Cox regression was applied to construct nomograms to predict patients’ prognoses. Moreover, we conducted in vitro experiments including CCK8, scratch, Transwell, and Matrigel assays to further explore the function of ACOT7 in LUAD. Results: Patients with high ACOT7 expression have notably poorer long-term survival in many cancer types, including LUAD. Further enrichment analyses reveal that ACOT7 is involved in immune cells’ infiltration and is substantially related to the cancer–immune microenvironment. ACOT7 could influence drug sensitivities, including afatinib, gefitinib, ibrutinib, lapatinib, osimertinib, sapitinib, taselisib, and PLX-4720 (all p < 0.01). A nomogram demonstrated a fair predictive value of ACOT7 in LUAD (C-index: 0.613, 95% CI: 0.568–0.658). The proliferation and migration of PC9 cells were significantly repressed when ACOT7 expression was downregulated. Conclusion: As an oncogene, ACOT7 is critical in the tumor microenvironment of pan-cancer and might be a novel therapeutic target for LUAD.