Down-regulation of Protease-activated Receptor 4 in Lung Adenocarcinoma is Associated with a More Aggressive Phenotype

Abstract

The role of protease-activated receptors (PARs) in lung tumors is controversial. Although PAR4 ispreferentially expressed in human lung tissues, its possible significance in lung cancer has not been defined. Thestudies reported herein used a combination of clinical observations and molecular methods. Surgically resectedlung adenocarcinomas and associated adjacent normal lung tissues were collected and BEAS-2B and NCI-H157cell lines were grown in tissue culture. PAR4 expression was evaluated by RT-PCR, RT-qPCR, Western blottingand immunohistochemistry analysis. The results showed that PAR4 mRNA expression was generally decreasedin lung adenocarcinoma tissues as compared with matched noncancerous tissues (67.7%) and was associatedwith poor differentiation (p=0.017) and metastasis (p=0.04). Western blotting and immunohistochemical analysisalso showed that PAR4 protein levels were mostly decreased in lung adenocarcinoma tissues (61.3%), and werealso associated with poor differentiation (p=0.035) and clinical stage (p=0.027). Moreover, PAR4 expression wasdecreased in NCI-H157 cells as compared with BEAS-2B cells. In conclusion, PAR4 expression is significantlydecreased in lung adenocarcinoma, and down-regulation of PAR4 is associated with a more clinically aggressivephenotype. PAR4 may acts as a tumor suppressor in lung adenocarcinoma.