Lactic Acid Metabolism-Related Gene May Act as a Prognostic Predictor by FARS2 in Nasopharyngeal Carcinoma

Abstract

Background

This study aimed to investigate the clinical value of lactic acid metabolism-related genes (LRGs) in nasopharyngeal carcinoma (NPC).

Methods

Clinical and genetic information was extracted from the TGCA and Gene Expression Omnibus databases. Consistency clustering was employed to identify NPC subpopulations. Immune infiltration was appraised using TIMER, ESTIMATE, and MCPCounter. Functional analysis was conducted to elucidate potential mechanisms. A prognostic risk model was successfully constructed using the LASSO algorithm and multivariate Cox regression analysis. Phenotypic experiments were conducted to validate the glycolysis and lactic acid metabolism.

Results

According to prognostically LRG genes, two clusters were identified and exhibited significant difference in immune landscape, which indicated variations in immune status. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes were predominantly implicated in immune-related pathways. These findings suggested that the LRG-based risk model could successfully predict the prognosis of NPC patients. Moreover, the risk model retained its predictive potency by stratifying patients with sex and age, with lower risk score patients displaying improved prognosis. In the training cohort, the low-risk group showed significantly lower stromal score, immune score, and ESTIMATE score compared with the high-risk group. To further enhance the precision of prognostic predictions, we developed a nomogram that integrated the risk model with clinical features. In the training cohort, the established nomogram could accurately predict the prognosis of NPC patients. Mechanically, the knockdown of FARS2 in NPC cells resulted in altered glycolysis and lactification. Deregulated FARS2 led to the accumulation of metabolic intensity, which resulted in the disruption of lactic acid metabolism.

Conclusion

These results highlighted the potential association between LRGs expression and immune dysfunction, which might contribute to adverse prognosis in NPC patients. This study represented a pioneering effort in exploring the prognostic value of LRGs in NPC.