Diminished expression of plasminogen activator inhibitor 2 correlates with local tumor aggressiveness in lung adenocarcinoma

Abstract

Lung cancer is notorious for high rates of local aggressiveness and metastasis. Decreased plasminogen activator inhibitor 2 (PAI2), an inhibitor of urokinase‐type plasminogen activator (uPA), was reported to correlated to lymph node metastasis and poor prognosis. However, the pathomechanism of PAI2 expression is still unknown. Therefore, we performed immunohistochemical staining on 105 non‐small cell lung cancer patients. Higher immunoreactivity was seen in tumors than in normal lung tissues (p<0.001). In adenocarcinoma, lower PAI2 expression correlated with higher T stage (p=0.02) and had trends associated with higher pTNM stage (p=0.06) and shorter overall survival (p=0.24). Besides, the involvement of matrix metalloproteinases (MMP) in the regulation between PAI2 and uPA was identified in bioinformatics database analysis. Here we showed decline of PAI2 level which was regulated by MMP caused overexpression of uPA and further led to local tumor aggressiveness and poor prognosis. In other words, overexpression of PAI2 may prevent the degradation by MMP in turn downregulate uPA to inhibit tumor invasion. In conclusion, our results suggested that PAI2 had more direct impact on local tumor progression than on metastasis. The correlation between diminished PAI2 expression and local tumor aggressiveness indicated that PAI2 may be a promising therapeutic and prognostic marker for lung adenocarcinoma.