The Role Of CMTM4 In Lung Squamous Cell Carcinoma And Its Preliminary Mechanism

Objective: To investigate the relationship between the clinicopathological characteristics and prognosis of lung squamous cell carcinoma and the expression of CMTM4 in lung squamous cell carcinoma tissues and aparacancerous tissues.Through in vitro cell function experiments,the effect of CMTM4 expression changes on the biological characteristics of lung squamous cells was clarified.Preliminary exploring the regulating mechanism of pulmonary squamous cell cancer invasion and metastasis.Methods: We detected the expression of CMTM4 in 90 pairs of lung squamous cell carcinoma tissues and aparacancerous tissues by immunohistochemistry.Chi-square test was used to analyze the correlation between CMTM4 expression and clinical significance in patients with lung squamous cell carcinoma.The correlation between the expression of CMTM4 and the survival time of patients with pulmonary squamous cell carcinoma was analyzed by Kaplan-Meier method and Log-Rank test.The CMTM4 overexpressing cell line was constructed by plasmid transfection,the relationship between the difference of CMTM4 expression and cell proliferation was detected by plate cloning experiment,and the change of cell migration and invasion ability were tested by transwell experiment.Western blotting was used to detect the changes of EMT-related factors in lung squamous cell carcinoma cells after CMTM4 expression changes.Results:(1)CMTM4 was positively expressed in 48/90(53%)cases of lung squamous cell carcinoma tissues,and was positively expressed in 79/90(88%)cases of paracancerous tissue,indicating that CMTM4 was lower in lung squamous cell carcinoma than in paracancerous tissue(P<0.05).(2)The expression of CMTM4 was significantly correlated with TNM staging(P<0.05).The patients with lung squamous cell carcinoma with negative expression of CMTM4 had a shorter survival time than those with positive expression of CMTM4.CMTM4 is an independent prognostic factor in patients with lung squamous cell carcinoma.(P<0.05).(3)The expression of CMTM4 was low in lung squamous cell carcinoma cells;compared with the control cells,the overexpression of CMTM4 resulted in decreased cell proliferation,decreased ability of monoclonal formation,and decreased ability of migration and invasion.(4)Western blot experiments found that overexpression of CMTM4 in lung squamous cell carcinoma cells NCI-H1703 can increase the levels of epithelial markers epithelial cell cadherin(E-cadherin)and β-catenin(β-cadherin),while the transcription factor zinc Finger protein(snail 1)decreased.Conclusion:(1)CMTM4 is lowly expressed in lung squamous cell carcinoma,and patients with lung squamous cell carcinoma with high CMTM4 expression have a longer postoperative survival and better prognosis than those with low CMTM4 expression.(2)In the lung squamous cell carcinoma cell line NCI-H1703 cells,overexpression of CMTM4 can significantly reduce the proliferation,invasion and migration ability of lung squamous carcinoma cells.(3)The expression level of E-cadherin,β-cadherin increased and the expression level of snail 1 decreased in CMTM4 overexpressed lung squamous carcinoma cell lines,suggesting that CMTM4 may inhibit epithelial-mesenchymal transition(EMT),thereby inhibiting the invasion and metastasis of lung squamous cell carcinoma,suggesting that CMTM4 is an independent prognostic factor in patients with lung squamous cell carcinoma.