Correlation of ARNTL2 with Immune Infiltration and Its Role as a Potential Prognostic Biomarker in Lung Adenocarcinoma

Abstract

ARNTL2 is a core component of the circadian clock genes and plays regulatory roles in the cell cycle and immune infiltration, but its mechanism in lung cancer (LC) remains unclear. To investigate the clinical and therapeutic value of ARNTL2 in LC. The Oncomine and Cancer Cell Line Encyclopedia (CCLE) databases were adopted for assessing the ARNTL2 expression, after which the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to assess the correlation of ARNTL2 with prognosis. The univariate and multivariate Cox regression analyses were utilized to identify independent prognostic factors. Also, we explored how ARNTL2 expression is related to immune infiltration, and immunomodulators in non-small lung cancer (NSCLC) using the Tumor Immune Estimation Resource (TIMER) database, TISIDB database and Gene Set Enrichment Analysis (GSEA). Finally, coexpression of ARNTL2 and PD-L1 in lung adenocarcinoma (LUAD) was verified via immunofluorescence staining and COXPRESdb v7 database. Our study demonstrated a remarkable upregulated expression of ARNTL2 in multiple cell lines and cancers, including NSCLC. Prognostic analysis displayed a remarkable correlation between high ARNTL2 expression and unfavorable overall survival (OS) and first progressive (FP) survival among patients ailing from LUAD, and ARNTL2 was an independent predictor of prognosis for LUAD patients. GSEA analysis showed that overexpression of ARNTL2 was significantly linked with cell cycle and immunity. Furthermore, we reported a correlation of ARNTL2 expression with immunomodulators and lymphocytes. Immunofluorescence staining revealed that ARNTL2 and PD-L1 were elevated relative to normal tissue for LUAD, and colocalization of them was observed. Elevated ARNTL2 expression in LUAD revealed the prognostic values and its prospective role as a target for cell cycle and immune therapy.