Upregulation of NDUFAF2 in Lung Adenocarcinoma Is a Novel Independent Prognostic Biomarker

Abstract

Background. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex assembly factor 2 (NDUFAF2) acts as a molecular chaperone for the assembly of complex I on the mitochondrial membrane, which is involved in the transfer of electrons in the respiratory chain. However, whether NDUFAF2 plays a role in lung adenocarcinoma (LUAD) is largely unexplored. Methods. Expression profiles were obtained from the TCGA and GEO databases and integrated via R3.6.3 and several bioinformatics platforms. Western blotting analysis and immunohistochemistry staining were used to examine the expressions of NDUFAF2 in clinical samples. Moreover, the diagnostic and prognostic value of NDUFAF2 expression level was also assessed. GO, KEGG, and gene set enrichment analysis (GSEA) were adopted to investigate NDUFAF2-related molecular functions, signaling pathways, and life activity processes. Results. NDUFAF2 was predominantly expressed in LUAD, and it is identified as a promising biomarker in the diagnosis of LUAD and its prognostic prediction. Overexpression of NDUFAF2 was correlated with N stage, T stage, and pathologic stage in LUAD, leading to worse overall survival (OS). Besides, the level of NDUFAF2 was independently associated with OS through a multivariate Cox analysis ( $\text{HR}=1.538$ , 95% (1.086-2.177), $P=0.015$ ). GO analysis revealed enrichment in innate immune response in mucosa and mucosal immune response, and GSEA indicated enrichment in G2_M_checkpoints, DNA replication, diseases of mitotic cell cycle, retinoblastoma gene in cancer, cell cycle pathway, and cell cycle. Furthermore, the expression level of NDUFAF2 was negatively correlated with infiltration levels of Tem, Tcm, NK CD56bright cells, and B cells. In contrast, the expression level of NDUFAF2 was positively correlated with the infiltration level of DCs and Th2 cells in LUAD patients. Conclusions. Collectively, NDUFAF2 is a promising independent prognostic biomarker and target in LUAD. In addition, NDUFAF2 might affect the prognosis of LUAD via DNA replication, diseases of mitotic cell cycle, cell cycle pathway, and cell cycle.