Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe

In this review the authors aimed to emphasize the practical value of nuclear expression of the mammary serine protease inhibitor (maspin), also known as serpin B5 protein, in colorectal carcinoma (CRC), from pre-malignant disorders to carcinogenesis and metastasis. As the role of maspin is controversial and not yet understood, the present update highlights the latest data revealed by literature which were filtrated through the daily experience of the authors, which was gained at microscopic examination of maspin expression in CRCs and other tumors for daily diagnosis. Data regarding the subcellular localization of maspin, in correlation with the microsatellite status, grade of tumor dedifferentiation, and epithelial-mesenchymal transition (EMT) phenomenon of the tumor buds were presented with details. An original observation refers to the maspin capacity to mark the tumor cells which are “at the point of budding” that were previously considered as having “hybrid EMT phenotype”. It refers to the transitional status of tumor cell that is between “epithelial status” and “mesenchymal status”. The second original hypothesis highlights the possible role of maspin in dysregulating the intestinal microbiota, in patients with idiopathic inflammatory bowel diseases (IBD) and inducing IBD-related CRC. The dynamic process of budding and EMT of tumor buds, possible mediated by maspin, needs further investigation and validation in many human CRC samples. The histological and molecular data reveal that synthesis of maspin-based therapeutics might represent a novel individualized therapeutic strategy for patients with CRC.

Clinicopathological and Prognostic Significance of Maspin Expression in Resected Non-Small Cell Lung Cancer: A Meta-Analysis

Objective To explore the association of maspin expression with clinical pathological parameters and prognosis in non-small cell lung cancer (NSCLC) who received the surgical therapy.Methods The EMBASE, Web of Science and PubMed were searched to identify eligible studies to 3 December, 2019. The correlation of maspin expression with clinicopathological characteristics and survival of resected NSCLC patients was assessed by the combined relative risk (RR) and hazard ratio (HR) with corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed via the Stata 12.0 software.Results A total of 12 articles involving 1771 patients were included. The results manifested that maspin was more prevalent in lung squamous cell carcinoma (SCC) (RR=0.36, 95% CI: 0.22-0.60, P＜0.001) and significantly associated with P53 expression (RR=1.50, 95% CI: 1.00-2.24, P=0.048), while no significant correlation of maspin with other clinicopathological parameters such as the gender, age, tumor size, lymph node metastasis, tumor node metastasis (TNM) stage or differentiation status was observed. As for the prognosis representing as overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS), only significant association between maspin and CSS (HR=1.58, 95% CI: 1.16-2.15, P=0.003) was revealed. However, the subgroup analysis for OS based on the histology demonstrated that maspin expression was an unfavourable and favourable prognostic indicator in lung adenocarcinoma (HR=3.36, 95% CI: 1.44-7.87, P=0.005) and SCC (HR=0.44, 95% CI: 0.27-0.71, P=0.001), respectively.Conclusion Maspin expression was correlated with histology type and P53 expression, but no certain association of maspin with other clinicopathological characteristics or prognosis was observed in resected NSCLC. More well-designed prospective researches with big samples are still needed to further assess the clinicopathological and prognostic significance of maspin in NSCLC patients undergoing surgical resection.

Clinicopathological and prognostic significance of maspin expression in resected non-small cell lung cancer: a meta-analysis

Objective To explore the association of maspin expression with clinical pathological parameters and prognosis in non-small cell lung cancer (NSCLC) who received the surgical therapy. Methods The EMBASE, Web of Science and PubMed were searched to identify eligible studies to 3 June, 2019. The correlation of maspin expression with clinicopathological characteristics and survival of resected NSCLC patients was assessed by the combined relative risk (RR) and hazard ratio (HR) with corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed via the Stata 12.0 software. Results A total of 12 articles involving 1771 patients were included. The results manifested that maspin was more prevalent in lung squamous cell carcinoma (SCC) (RR=0.36, 95% CI: 0.22-0.60, P <0.001) and significantly associated with P53 expression (RR=1.50, 95% CI: 1.00-2.24, P =0.048), while no significant correlation of maspin with other clinicopathological parameters such as the gender, age, tumor size, lymph node metastasis, tumor node metastasis (TNM) stage or differentiation status was observed. As for the prognosis representing as overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS), only significant association between maspin and CSS (HR=1.58, 95% CI: 1.16-2.15, P =0.003) was revealed. However, the subgroup analysis for OS based on the histology demonstrated that maspin expression was an unfavourable and favourable prognostic indicator in lung adenocarcinoma (HR=3.36, 95% CI: 1.44-7.87, P =0.005) and SCC (HR=0.44, 95% CI: 0.27-0.71, P =0.001), respectively. Conclusion Maspin expression was correlated with histology type and P53 expression, but no certain association of maspin with other clinicopathological characteristics or prognosis was observed in resected NSCLC. More well-designed prospective researches with big samples are still needed to further assess the clinicopathological and prognostic significance of maspin in NSCLC patients undergoing surgical resection.

Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer

Maspin is a member of the clade B serine protease inhibitor superfamily and exhibits diverse regulatory effects in various types of solid tumors. We compared the expressions of maspin and determined its potential biological functions and regulatory mechanisms in bladder carcinoma cells in vitro and in vivo. The results of RT-qPCR indicated that maspin expressed significantly lower levels in the bladder cancer tissues than in the paired normal tissues. The immunohistochemical assays of human bladder tissue arrays revealed similar results. Maspin-knockdown enhanced cell invasion whereas the overexpression of maspin resulted in the opposite process taking place. Knockdown of maspin also enhanced tumorigenesis in vivo and downregulated protein levels of acetyl-histone H3. Moreover, in bladder carcinoma cells, maspin modulated HDAC1 target genes, including cyclin D1, p21, MMP9, and vimentin. Treatment with MK2206, which is an Akt inhibitor, upregulated maspin expression, whereas PTEN-knockdown or PTEN activity inhibitor (VO-OHpic) treatments demonstrated reverse results. The ectopic overexpression of p53 or camptothecin treatment induced maspin expression. Our study indicated that maspin is a PTEN-upregulated and p53-upregulated gene that blocks cell growth in vitro and in vivo, and may act as an HDAC1 inhibitor in bladder carcinoma cells. We consider that maspin is a potential tumor suppressor gene in bladder cancer.