The Relationship Between TMPRSS4 Gene Expression In Early-Stage Non-Small Cell Lung Cancer And Tumor Angiogenesis

Background and Objective:Transmembrane protease serines (TMPRSSs) are expressed in some normal organs and tumor tissues. Thus far, multiple TMPRSSs members have been found in humans. Transmembrane serine protease 4 (TMPRSS4) is one of the members of the type II transmembrane serine protease (TTSPs) family that is located in on chromosome 11 q23.3. Its full length cDNA is 4.1 kb, and the weight of its encoded peptide molecular containing 437 amino acid residues is 48 kDa. The original discoverers thought that this enzyme was simply involved in some non-specific protein hydrolytic process. However,further research on TMPRSSs revealed that they also participate in many complicated physiological processes in the body, including the cell cycle, cell migration, cell proliferation, blood pressure regulation and angiopoiesis. Additionally, the dysfunction of TMPRSSs can lead to neurodegenerative disease, metabolic disease, cardiovascular disease and cancer. TMPRSS4 protein expressed on the cell surface of certain organs and tumors has the potential function to degrade the cell membrane and extracellular matrix. Thus, it can promote the proliferation and metastasis of tumor cells. The latest studies have shown that the expression of the TMPRSS4 gene was obviously up-regulated in NSCLC, revealing the close relationship between unusually high TMPRSS4 gene expression and the occurrence and development of NSCLC [24]. This study was aimed to investigate the abnormal expression of Transmembrane Protease Serine 4 (TMPRSS4) associated with tumor angiogenesis and its clinical significance in patients with early-stage non-small cell lung cancer (NSCLC).Research Methods:All samples were collected from 87 patients with the exact diagnosis of stage I NSCLC and complete clinical follow-up data from January 2009 to January 2010. These selected patients all had received pulmonary lobectomy and regional lymph node dissection at the Department of Thoracic Surgery of Qilu Hospital. Additionally,50 samples used as pericarcinous tissues were taken from lung tissues from the tumor edge 0.5 cm. Samples from the 30 cases used as negative controls were taken from normal lung tissues more than 5 cm from the outer edge of the tumor tissues. All specimens were collected during surgery. These specimens were next fixed by 4% formalin and embedded in paraffin. The tissues were cut into 5-μm serial sections and then detected by immunohistochemistry. For Real-time PCR analysis,14 matched pairs of tumors tissue and adjacent noncancerous tissue samples were obtained from pulmonary lobectomy specimens of patients diagnosed with NSCLC immediately after surgery between Sep 2014 and Oct 2014 in our department. All patients received no preoperative chemotherapy and radiotherapy and pathologically diagnosed with Early-Stage NSCLC. All statistical analyses were executed using SPSS 13.0 statistical software. We used chi-squared test to detect the correlation between TMPRSS4 protein expression and MVD, and the associations between TMPRSS4 protein expression or MVD and clinicopathologic characteristics. The difference between groups was identified using the statistical significance for P value< 0.05.Results:The positive expression rates of TMPRSS4 protein in lung cancerous tissues, adjacent tissues and normal lung tissues were 60.9%, 30.0% and 16.7%, respectively, with a rate in lung cancer tissues and adjacent tissues higher than that in normal lung tissues (p<0.05). The relative expression of TMPRSS4 mRNA in tumor and normal lung tissues are(1.826±0.453) and(0.829±0.366), Respectively. TMPRSS4 mRNA expression level in NSCLC cancer tissues was significantly higher than the adjacent normal lung tissues (p<0.05). MVD in cancerous tissue with TMPRSS4 protein high expression was significantly higher than that of low TMPRSS4 protein expression of carcinoma tissue (p<0.05). TMPRSS4 protein expression in cancerous tissue of T2 was significantly higher than that of T1 carcinoma tissue (p<0.05). The MVD in T2 cancerous tissue was significantly higher than that of T1 carcinoma tissue (p<0.05).Conclusion:TMPRSS4 high protein expression in early-stage non-small cell lung cancerous tissue was significantly associated with high MVD. High TMPRSS4 protein expression and high MVD in cancer tissue were closely related to the tumor infiltration depth. TMPRSS4 may become a new target for early NSCLC patients with cancer treatment.