Plasminogen activator inhibitor-2 plays a leading prognostic role among protease families in non-small cell lung cancer
Journal
PLoS ONE
Journal Volume
10
Journal Issue
7
Date Issued
2015
Author(s)
Su, C.-Y.
Abstract
Background In lung cancer, uPA, its receptor (uPAR), and the inhibitors PAI-1 and PAI-2 of the plasminogen activator family interact with MMP-2 and MMP-9 of the MMP family to promote cancer progression. However, it remains undetermined which of these markers plays the most important role and may be the most useful indicator to stratify the patients by risk. Methods We determined the individual prognostic value of these 6 markers by analyzing a derivation cohort with 98 non-small cell lung cancer patients by immunohistochemical staining. The correlation between the IHC expression levels of these markers and disease prognosis was investigated, and an immunohistochemical panel for prognostic prediction was subsequently generated through prognostic model analysis. The value of the immunohistochemical panel was then verified by a validation cohort with 91 lung cancer patients. Results In derivation cohort, PAI-2 is the most powerful prognostic factor (HR = 2.30; P = 0.001), followed by MMP-9 (HR = 2.09; P = 0.019) according to multivariate analysis. When combining PAI-2 and MMP-9, the most unfavorable prognostic group (low PAI-2 and high MMP-9 IHC expression levels) showed a 6.40-fold increased risk of a poor prognosis compared to the most favorable prognostic group (high PAI-2 and low MMP-9 IHC expression levels). PAI-2 and MMP-9 IHC panel could more precisely identify high risk patients in both derivation and validation cohort. Conclusions We revealed PAI-2 as the most powerful prognostic marker among PA and MMP protease family even after considering their close relationships with each other. By utilizing a combination of PAI-2 and MMP-9, more precise prognostic information than merely using pathological stage alone can be obtained for lung cancer patients. Copyright: ? 2015 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
gelatinase A; gelatinase B; plasminogen activator inhibitor 1; plasminogen activator inhibitor 2; urokinase; urokinase receptor; gelatinase B; peptide hydrolase; plasminogen activator inhibitor 2; tumor marker; Article; cancer patient; cancer prognosis; cancer staging; cancer survival; comparative study; controlled study; disease association; disease free survival; down regulation; high risk patient; human; human tissue; immunohistochemistry; lung adenocarcinoma; major clinical study; non small cell lung cancer; overall survival; protein analysis; protein expression; protein function; receiver operating characteristic; sensitivity and specificity; upregulation; female; lung tumor; male; metabolism; middle aged; multivariate analysis; non small cell lung cancer; pathology; prognosis; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Matrix Metalloproteinase 9; Middle Aged; Multivariate Analysis; Peptide Hydrolases; Plasminogen Activator Inhibitor 2; Prognosis
Type
journal article