Overexpression of abnormal spindle-like microcephaly-associated (ASPM) increases tumor aggressiveness and predicts poor outcome in patients with lung adenocarcinoma

Abstract

Background: Cumulative evidence points to abnormal spindle-like microcephaly-associated (ASPM) protein being overexpressed in various cancers, and the aberrant expression of ASPM has been shown to promote cancer tumorigenicity and progression. However, its role and clinical significance in lung adenocarcinoma (LUAD) remains unclear. This study aimed to determine the expression patterns of ASPM and its clinical significance in LUAD. Methods: In total, 4 original worldwide LUAD microarray mRNA expression datasets (N=1,116) with clinical and follow-up annotations were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The expression of ASPM protein in LUAD patients was detected by immunohistochemistry. Survival analysis and Cox regression analysis were used to examine the prognostic value of ASPM expression. Gene set enrichment analysis (GSEA) was performed to investigate the relationship between ASPM and LUAD. Results: Dataset analyses and immunohistochemistry revealed that ASPM expression was significantly higher in the LUAD tissues compared with normal lung tissues, especially in the advanced tumor stage. Additionally, overexpression of ASPM was significantly correlated with shorter overall survival (OS) and relapse-free survival (RFS) in LUAD. Univariate and multivariate Cox regression analyses revealed that the overexpression of ASPM was a potential independent predictor of poor OS and RFS. However, ASPM overexpression was not significantly associated with predicting OS in lung squamous cell carcinoma. GSEA analysis demonstrated that ASPM was significantly enriched in the cell cycle, DNA replication, homologous recombination, RNA degradation, mismatch repair, and p53 signaling pathways. Conclusions: These findings demonstrate the important role of ASPM in the tumorigenesis and progression of LUAD.