Abstract
Accumulating studies have confirmed that mammary serine protease inhibitor (MASPIN) plays an essential role in non-small cell lung cancer (NSCLC). However, results are still controversial or inconsistent. In the present study, we attempted to identify the clinical significance of MASPIN and its potential molecular roles in NSCLC. The correlation of MASPIN with prognosis and clinicopathological characteristics was assessed by meta-analysis. Additionally, the potential molecular mechanisms of MASPIN in NSCLC was also investigated through several online databases. A total of 2220 NSCLC patients from 12 high quality studies were included and the results indicated that up-regulated MASPIN nucleus and cytoplasm expression was associated with poor overall survival (OS) (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.01–2.04, P<0.05), elevated MASPIN cytoplasm expression was associated with poor OS (HR = 1.45, 95% CI = 1.01–2.07, P<0.05), disease-free survival (DFS) (HR = 1.95, 95% CI = 1.31–2.88, P=0.001), and disease-specific survival (DSS) (HR = 2.17, 95% CI = 1.18–3.99, P=0.013). MASPIN both nucleus and cytoplasm location were associated with clinicopathological characteristics. Bioinformatics analysis validated the above results and suggested that human serpin family B member 5 (SERPINB5) hypomethylated levels were negatively correlated with its mRNA expression. Bioinformatics analysis also revealed the 85 most frequently altered neighboring genes of SERPINB5, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed 20 GO terms and 3 KEGG pathways with statistical significance. MASPIN had a statistically negative correlation with NSCLC prognosis, functioning as an oncoprotein by hypomethylation and influencing specific pathways involving the 85 genes identified herein. MASPIN might be a promising prognostic signature in NSCLC.
Highlights
The mammary serine protease inhibitor (MASPIN), encoded by the human serpin family B member 5 (SERPINB5) gene, was first reported in 1994 as a tumor suppressor [1]
A total of 2220 non-small cell lung cancer (NSCLC) patients from 12 high quality studies were included and the results indicated that up-regulated MASPIN nucleus and cytoplasm expression was associated with poor overall survival (OS) (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.01–2.04, P
Inclusion criteria for studies: (1) participants were pathologically diagnosed with NSCLC; (2) the expression and subcellular localization were detected by immunohistochemistry; (3) patients were divided into high and low expression groups according to MASPIN expression and the relationship between MASPIN and NSCLC prognosis (such as overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS)) and clinicopathological characteristics were described; (iv) relevant data were sufficient to obtain hazard ratio (HR) and corresponding 95% confidence interval (CI); (v) cohort studies
Summary
The mammary serine protease inhibitor (MASPIN), encoded by the human serpin family B member 5 (SERPINB5) gene, was first reported in 1994 as a tumor suppressor [1]. MASPIN subcellular localization appears linked to its biological functions [5], and its nuclear localization indicates a more favorable prognosis in human malignancies, such as breast cancer [6], pancreatic cancer [4], and ovarian carcinoma [7]. This phenomenon appears in non-small cell lung cancer (NSCLC) [8], which is one of the most familiar malignant tumors [9,10] and can be mainly divided
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