DARS2 is a prognostic biomarker and correlated with immune infiltrates and cuproptosis in lung adenocarcinoma

Am J Cancer Res. 2023 Mar 15;13(3):818-834. eCollection 2023.

Abstract

Overexpression of DARS2 may enhance the progression of hepatocellular carcinoma (HCC). However, there are few extensive reports on DARS2 function in lung adenocarcinoma (LUAD). The differential expression of DARS2 was detected by genomics and in vitro experiments, and the effect of DARS2 expression on LUAD cell activity was analyzed. Functional enrichment analysis was performed to explore possible signal pathways involved in the biological functions of DARS2 and its co-expressed genes. Utilizing TIMER and GEPIA datasets, the association between DARS2 expression and immunological infiltrating cells was analyzed. At the same time, the association between DARS2 expression pattern and LUAD m6A modification and cuproptosis was examined utilizing TCGA and GEO datasets. The level of DARS2 in LUAD increased, and inhibition of DARS2 expression could significantly inhibit the proliferation of LUAD cells. ROC curves showed that DARS2 overexpression could accurately diagnose LUAD and lead to a significant decline in the survival rates of OS, DSS, and PFI in LUAD. Enrichment analysis showed that DARS2 and its co-expressed genes were closely associated with chromosome segregation and the cell cycle. TIMER and GEPIA database analysis demonstrated that the DARS2 expression pattern was adversely correlated with the infiltration of B cells and Tfh cells. TCGA and GEO dataset examination revealed that DARS2 expression was significantly linked to four m6A-related genes and one cuproptosis-related gene. DARS2 expression is increased in LUAD patients and is closely associated with LUAD immune cell infiltration, modification of m6A, and cuproptosis. DARS2 is a potential reliable prognostic biomarker of LUAD.

Keywords: DARS2; cuproptosis; immune infiltration; lung adenocarcinoma; m6A modification.