Acetyl-CoA acyltransferase 1 is a potential tumor suppressor gene associated with immune cell infiltration in nasopharyngeal carcinoma

Abstract

Acetyl-CoA acyltransferase 1 (ACAA1), encoding the protein peroxisomal 3-ketoacyl-CoA thiolase (POT1), plays a vital role in the fatty acid beta-oxidation system. ACAA1 has been implicated in the carcinogenesis and development of various human cancers. In this study, the downregulation of ACAA1 was observed consistently throughout the progression of nasopharyngeal carcinoma (NPC) and showed a negative correlation with the expression of EBV-encoded genes. Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) curve suggested the potential of ACAA1 in predicting NPC prognosis. Through in vitro and in vivo experiments, we identified that the overexpression of ACAA1 inhibited the proliferation, migration, and invasion of NPC cells, which was further confirmed by reduced Ki-67 staining and actin filaments redistribution. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analyses indicated significant enrichment of immune-related pathways in NPC cells with higher ACAA1 expression. Furthermore, data from the xCell, ESTIMATE and Immunophenoscore analysis supported a critical role of ACAA1 in modulating immune cell infiltration and tumor immune environment of NPC. Interestingly, low expression of ACAA1 was significantly associated with NPC patients classified as tumor microenvironment (TME) subtype 1 and with poor outcome. Expression pattern analyses revealed a positive correlation between ACAA1 expression and six immune checkpoint-related genes, including CD27, PDCD1, CD86, BTLA, TIGIT, and CD28. Taken together, our study reveals that ACAA1 is a potential tumor suppressor gene, which may participate in immune evasion in NPC. ACAA1 could serve as a novel prognosis and therapeutic biomarker for NPC patients.