Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Nanjing University of Chinese Medicine, Nanjing, China.
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20200743.
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.
越来越多的研究证实，乳腺丝氨酸蛋白酶抑制剂（MASPIN）在非小细胞肺癌（NSCLC）中发挥着重要作用。然而，结果仍存在争议或不一致。在本研究中，我们试图确定 MASPIN 的临床意义及其在 NSCLC 中的潜在分子作用。通过荟萃分析评估 MASPIN 与预后和临床病理特征的相关性。此外，还通过几个在线数据库研究了 MASPIN 在 NSCLC 中的潜在分子机制。共纳入了 12 项高质量研究中的 2220 名 NSCLC 患者，结果表明，核和细胞质中上调的 MASPIN 表达与总生存期（OS）不良相关（风险比（HR）=1.43，95%置信区间（CI）=1.01-2.04，P<0.05），细胞质中上调的 MASPIN 表达与 OS 不良相关（HR=1.45，95%CI=1.01-2.07，P<0.05），无病生存期（DFS）（HR=1.95，95%CI=1.31-2.88，P=0.001）和疾病特异性生存期（DSS）（HR=2.17，95%CI=1.18-3.99，P=0.013）。MASPIN 的核和细胞质定位均与临床病理特征相关。生物信息学分析验证了上述结果，并表明人丝氨酸蛋白酶抑制剂家族 B 成员 5（SERPINB5）的低甲基化水平与其 mRNA 表达呈负相关。生物信息学分析还揭示了 SERPINB5 最常改变的 85 个相邻基因，GO 和 KEGG 通路富集分析显示有 20 个 GO 术语和 3 个 KEGG 通路具有统计学意义。MASPIN 与 NSCLC 预后呈统计学负相关，通过低甲基化发挥癌蛋白作用，并影响涉及本文鉴定的 85 个基因的特定通路。MASPIN 可能是 NSCLC 有前途的预后标志物。
