Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas, based on the 2011 IASLC/ATS/ERS classification

Abstract

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma.

Keywords: angiogenesis; lung invasive adenocarcinoma; metastasis-associated protein 1; microvessel density; prognosis.

Figure 1.

Immunohistochemical staining of lung invasive adenocarcinoma specimens, displaying (A) low and (B) high protein expression levels of metastasis-associated protein 1, respectively. (C) Intratumoral microvessels were immunopositive for cluster of differentiation 105 (magnification,×200).

Figure 2.

Mann-Whitney U test demonstrated that tumors with high protein expression levels of MTA1 exhibited significantly higher intratumoral microvessel density than tumors with low protein expression levels of MTA1 (P=0.015). MTA1, metastasis-associated protein 1.

Figure 3.

Kaplan-Meier curves of (A) disease-free and (B) overall survival, stratified according to the protein expression levels of MTA1. Log-rank test demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those with low protein expression levels of MTA1 (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). MTA1, .metastasis-associated protein 1.