Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma

Abstract

Background:Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue.Methods:PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses.Results:Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = −2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = −2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ2 = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499–4.367, P = 0.001).Conclusion:These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.

Construction of a circRNA‐miRNA‐mRNA network to explore the pathogenesis and treatment of pancreatic ductal adenocarcinoma

“…A previous study demonstrated that SERPINE1 is significantly associated with survival in PDAC patients, which is not in accord with other reports . Based on the results of the survival analysis in the present study, expression of SERPINE1 is negatively related to the survival of PDAC patients.…”

PAI-1 derived from cancer-associated fibroblasts in esophageal squamous cell carcinoma promotes the invasion of cancer cells and the migration of macrophages

“…PAI-1, encoded by SERPINE1, is a member of the serpin superfamily and is an essential inhibitor of tissue plasminogen activator and urokinase-type (uPA), activators of plasminogen; PAI-1 can also bind LRP1, a major endocytic receptor [21,22]. The role of PAI-1 in thrombosis is generally known, and elevated PAI-1 levels in tumor tissues correlate with poor prognosis in patients with certain cancers (e.g., esophageal cancer, head and neck squamous cell carcinoma, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, and urothelial carcinoma) [23][24][25]. Our findings identified CAFs as an important source of PAI-1 in the ESCC microenvironment.…”

Upregulation of Atypical Cadherin FAT1 Promotes an Immunosuppressive Tumor Microenvironment via TGF-β

“…In fact, glioma patients displaying a high expression of Serpine1 in biopsies have been known to show shorter overall survival (53). In other tumors as well, such as hepatocellular carcinoma, pancreatic ductal adenocarcinoma, and cervical cancer, high Serpine1 expression has been associated with a poor clinical outcome (54)(55)(56).…”