GRSF1 predicts an unfavorable prognosis and promotes tumorigenesis in lung adenocarcinoma based on bioinformatics analysis and in vitro validation

Background: Effective biomarkers play a critical role in improving clinical approaches to treat lung adenocarcinoma (LUAD). However, many existing biomarkers have limitations due to a lot of factors, requiring the development of additional biomarkers to effectively predict the disease course and prognosis of LUAD. Guanine-rich RNA sequence binding factor 1 (GRSF1) participates in multiple biological processes, but its regulatory effect on LUAD remains unknown. The present study aimed to investigate the clinicopathological importance and biological role of GRSF1 in LUAD. Methods: The expression of GRSF1 was evaluated using multiple service portals. X-Tile software were used to determine the high and low GRSF1 groups and the relationships between GRSF1 expression and clinicopathological characteristics were then analyzed by R packages. Besides, prognostic significance was identified by the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (K-M) Plotter. Overall survival (OS) and disease-free survival (DFS) was the main outcome of prognosis analysis. The DNA copy number alterations (CNAs) and methylations were calculated using cBioPortal and R packages. The co-expressed genes of GRSF1 were obtained from LinkedOmics, and functional networks were then constructed by R clusterProfiler. Additionally, cell counting kit 8 (CCK-8) and colony formation assays were applied to verify the proliferation effects of GRSF1 on LUAD cells. Results: GRSF1 was significantly upregulated in the LUAD tissues compared to the non-tumor lung tissues (all P<0.05), and its expression was significantly correlated with gender (chi(2)=6.873, P=0.009) and T classification (chi(2)=13.62, P=0.003). Higher GRSF1 expression indicated worse OS [hazards ratio (HR)=1.6, P=0.0022] and DFS (HR=1.4, P=0.043), which suggested that GRSF1 was an independent prognostic factor for LUAD. DNA gain/amplification and hypomethylation may also contribute to GRSF1 upregulation. The functional annotation showed that GRSF1 regulates tumorigenesis through several signaling pathways. The knockdown of GRSF1 significantly suppressed lung cancer cell proliferation in vitro. Conclusions: The high expression of GRSF1 indicated an unfavorable prognosis and was closely related to LUAD tumor occurrence and development, which could be used as an effective prognostic biomarker for patients suffering from LUAD.