B3GNT3 as a prognostic biomarker and correlation with immune cell infiltration in lung adenocarcinoma

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant cancer in humans and because of low long-term survival rates, exploration of the molecular mechanisms underlying its progression, as well as novel prognostic predictors, is urgently needed. B3GNT3, a type II transmembrane protein located in the Golgi apparatus, is essential for forming extended core 1 oligosaccharides and is reportedly involved in malignant transformation. METHODS: The Cancer Genome Atlas (TCGA) and GSE68465 were used to analyze the expression of B3GNT3 in LUAD and normal tissues and overall survival. Real time quantitative polymerase chain reaction (qPCR) and western blot were conducted to measure the mRNA and protein levels of B3GNT3, respectively. Functional enrichment of differentially expressed genes was explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We performed univariate and multivariate Cox regression analyses and a meta-analysis to reveal an independent factor for LUAD. We evaluated the correlation between immune infiltration levels and cumulative survival in the TIMER database. The correlation between B3GNT3 and immune cell infiltration was assessed via Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The association of DNA methylation of B3GNT3 and prognosis was determined. A nomogram that incorporated expression and clinical features was additionally built for prognostic prediction. Cell proliferation, cloning, and invasion were conducted to validate the roles of B3GNT3 in LUAD. RESULTS: B3GNT3 was more highly expressed in LUAD tissues than in normal lung tissues, consistent with the mRNA and protein levels in LUAD cells. B3GNT3 was an independent factor for LUAD. Moreover, the levels of B3GNT3 were related to immune cell infiltration in LUAD microenvironments. DNA methylation of B3GNT3 correlated with the mRNA of B3GNT and overall survival of LUAD patients. The expression of B3GNT3 was highly valuable for the prediction of diagnosis. Knockdown of B3GNT3 inhibited LUAD cell viability and cloning ability, and hindered invasion. CONCLUSIONS: B3GNT3 was highly associated with immune cell infiltration, acting as an important biomarker for the prognosis and diagnosis of LUAD.