The Study On Protein Levels Of Two Candidate Tumor Suppressors TIMP2, Decorin In Lung Cancer Tissue And Plasma

BACKGROUND&AIM:Lung cancer is the leading cause of cancer deaths throughout the world. In previous study, we provide a novel method to detect free proteins that released to plasma by tumor cells to establish lung cancer-related protein profiles in blood. We analyzed the proteins released into serum-free conditioned medium (CM) by lung cancer and adjacent normal bronchial cells by short-time culture, and established lung cancer related database (over1200proteins) including TIMP2and Decorin. Tissue inhibitors of metalloproteinases (TIMPs) have been shown to perform several biological functions in tumor promotion. Decorin (DCN) protein is a component of extracellular matrix, and plays a role in matrix assembly. This protein is capable of suppressing the tumor cell growth. The aim of this study is to examine protein levels of Decorin in tissue samples of non-small cell lung cancer patients, and evaluate its potential clinical value.METHODS:â‘ Plasma TIMP2level in114patients with primary lung cancer,16patients with Pneumonia, and in100health subjects were measured by an enzyme immunoassay (ELISA). Ninety seven specimens from patients (same group with above) with primary lung cancer were also examined by immunohistochemistry(IHC).â‘¡The Decorin protein levels in tumor tissues and corresponding normal tissues from16cases of lung squamous cell carcinoma were analyzed by Western blot analysis. Fifty one cases with non-small cell lung cancer (NSCLC), tumor tissues and normal lung tissues were examined by immunohistochemical (IHC) analysis.RESULTS:â‘ ELISA results showed that the plasma levels of TIMP2in patients with primary lung cancer were significantly lower than the healthy controls (P<0.001). The TIMP2levels in advanced group (Stage â…¢+â…£) were significantly higher than those in non advanced group (Stage â… +â…¡). The plasma TIMP2levels were elevated in the patients with distant metastatic than that without (P<0.001). IHC results showed that TIMP2positive rate in lung cancer tissues was30.85%, significantly lower than normal alveoli and bronchial (P<0.001).â‘¡Western blot results showed that75.0%(12/16) of patients with lung squamous cell carcinoma, the Decorin protein level in the tumor tissues was lower than that in the corresponding normal lung tissues. IHC results showed that positively stained Decorin was detected in only11.8%of the tumor tissues, which was significantly lower than that observed in normal alveoli tissues (51.1%, P<0.001). In lung adenocarcinoma (ADC) there was almost no expression of Decorin, significantly lower than that in squamous cell carcinoma (SCC)(,P=0.006).CONCLUSION:â‘ The low TIMP2plasma level and down-regulated expression level in lung cancer tissues may happen in early stage of carcinogenesis, the homeostasis of TIMP2and MMPs was broken, TIMP2can't block the activity of MMPs, which is important in inhibiting tumorigenesis and subsequent malignant progression.â‘¡The decreased levels of Decorin protein in tissue samples especially in ADC, indicated Decorin may play a role in lung cancer carcinogenesis.