Significance of TRPM8 protein expression in lung adenocarcinoma

AIM To investigate the significance of transient receptor potential cation channel subfamily M member 8 （TRPM8） protein expression in lung adenocarcinoma. METHODS The tumor samples from 112 cases of patients with lung adenocarcinoma were collected in our hospital， and 4~5 years of follow-up was conducted. The protein expression of TRPM8 was analyzed by immunohistochemical staining， and the correlations between the TRPM8 protein expression and the clinical characteristics including prognosis of the patients with lung adenocarcinoma were investigated. After TRPM8 protein expression was up-regulated in A549 lung adenocarcinoma cells by lentiviral infection， the proliferation of A549 cells was analyzed by CCK-8 assay and colony formation assay， the cell cycle and apoptosis were analyzed by flow cytometry， and the migration and invasion abilities of the cells were measured by scratch experiment and Transwell assay. The TRPM8 protein expression was stably up-regulated in H1299 cells by lentiviral infection， and then the left and right buttocks of the immunodeficient mice were subcutaneously injected with empty vector control cells and TRPM8-overexpressing cells， respectively. The effects of TRPM8 on the growth of H1299 cell-derived xenograft tumor in immunodeficient mice were evaluated. RESULTS The 4~5-year survival rate in the patients with high TRPM8 protein expression was significantly higher than that in the patients with low expression of TRPM8 protein （P=0.017）. The tumor maximum diameter in the patients with high TRPM8 protein expression was significantly smaller than that in the patients with low TRPM8 protein expression （P=0.028）. The viability， the number of colonies and the migration and invasion abilities of TRPM8-overexpressing A549 cells were significantly decreased as compared with empty vector and parental cells （P<0.01）. The results of flow cytometry analysis showed that the proportion of A549 cells at S stage was significantly increased in TRPM8 overexpression group as compared with empty vector group （P<0.01）. The growth rate and the weight of TRPM8-overexpressing H1299 cell-derived xenograft tumor in immunodeficient mice were significantly lower than those in empty vector group （P<0.01）. CONCLUSION TPRM8 is a tumor suppressor in lung adenocarcinoma， and low expression of TRPM8 protein was a poor prognositic indicator of patients with lung adenocarcinoma.