PAFAH1B3 Predicts Poor Prognosis and Promotes Progression in Lung Adenocarcinoma

Abstract

\n Background\n\nRecently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, the role in lung adenocarcinoma (LUAD) has not been reported until now.\nMethods\n\nExpression of PAFAH1B3 in LUAD was determined by Gene Expression Profiling Interactive Analysis (GEPIA), real-time PCR (RT-PCR), Western blot and Immunohistochemical (IHC) analysis. LUAD datasets with clinical information were obtained from The Cancer Genome Atlas Program (TCGA). Chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyzed the prognostic value of PAFAH1B3. CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and cell cycle. Western blot was performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) was used to analyze the effect of PAFAH1B3 on immune cell infiltration.\nResults\n\nOur study showed that PAFAH1B3 was upregulated in LUAD, and silencing PAFAH1B3 suppressed cell proliferation, colony formation, invasion and increased the cell population in G0-G1 phases in vitro. In addition, tissue microarray IHC analysis showed that the PAFAH1B3 protein level was remarkably correlated with distant metastasis, TNM stage and clinical outcome. Furthermore, multivariate cox regression analysis based on TCGA-LUAD datasets and tissue microarray indicated that PAFAH1B3 was an independent prognostic risk factor for LUAD patients. Moreover, knockdown of PAFAH1B3 inhibited EMT in LUAD cells and PAFAH1B3 mRNA expression was correlated with immune infiltrates.\nConclusion\n\nOur studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.