CHD1L Contributes To The Invasiveness And Metastasis By Up-Regulating SPOCK1 In Non-Small-Cell Lung Cancer

Objective:By clinical researches and in vitro experiments,we studied the expression of CHD1 L in non-small-cell lung cancer(NSCLC)patients.And analyzed the relationship between CHD1 L expression and clinicopathological parameters and prognosis of NSCLC patients.After knocking down CHD1 L by RNAi technology,we analyzed the changes in the invasiveness and metastasis of lung adenocarcinoma cell lines.And researched the molecular mechanism of CHD1 L through the downstream gene SPOCK1 to promote tumor invasiveness and metastasis.It provided new ideas for early diagnosis,clinical treatment,and prognosis of NSCLC.Method:1.A total of 284 NSCLC paraffin-embedded tumor tissues(150 adenocarcinomas,134 squamous carcinomas)were collected from the Department of Pathology of Shanxi Cancer Hospital,between January 2017 and December 2017.Meanwhile,we selected 54 cases of squamous cell carcinoma adjacent to normal tissues and 39 cases of adenocarcinoma adjacent to normal tissues as controls,then made tissue microarrays respectively.2.Immunohistochemistry(IHC)was used to detect the expression of CHD1 L protein in NSCLC and analyzed the relationship between CHD1 L protein expression and its clinical pathological parameters and prognosis.3.RNAi technology was used to knock down the expression of the CHD1 L in lung adenocarcinoma cell lines.Trans-well tests and wound-healing tests were used to detect the changes of lung adenocarcinoma cell line’s invasion and migration ability.To explore the molecular mechanism of CHD1 L in NSCLC,western-blot and immunofluorescence tests were used to detect the expression of CHD1 L and its downstream genes SPOCK1 and metastasis-related genes Vimentin and MMP2.Results:1.IHC results showed that CHD1 L protein was mainly located in the nucleus of tumor tissue.The overexpression rate of CHD1 L in lung adenocarcinoma tissue was 51%(68/134),which was significantly higher than that of 5%(2/39)in normal tissue adjacent to adenocarcinoma,the difference was statistically significant(P<0.05).The overexpression rate of CHD1 L in lung squamous cell carcinoma was 27%(41/150),which was significantly higher than that of 2%(1/54)in normal tissues adjacent to lung squamous cell carcinoma,the difference was statistically significant(P<0.05).The overexpression rate of CHD1 L in lung adenocarcinoma was significantly higher than that of in lung squamous cell carcinoma,the difference was statistically significant(P<0.05).And in lung adenocarcinoma,the overexpression of CHD1 L is related to its lymph node metastasis and clinical stage,the difference was statistically significant(P<0.05).2.The overexpression rate of CHD1 L in under 60 years old NSCLC patients was 46%(56/123),which was significantly higher than that of 33%(53/161)in over 60 years old patients,the difference was statistically significant(P<0.05).The overall survival rate of CHD1 L overexpression patients was lower than that of low expression lung adenocarcinoma patients under 60 years old(P<0.05)and lung squamous carcinoma patients over 60 years old(P<0.05),the difference was statistically significant.3.After knocking down CHD1 L by RNAi technology,the invasiveness and metastasis of lung adenocarcinoma cells decreased.At the same time,the protein content of its downstream genes SPOCK1 and EMT-related genes Vimentin and MMP2 also decreased.Conclusion:1.CHD1 L may be involved in the occurrence and development of NSCLC.At the same time,CHD1 L may play a certain role in the younger age of non-small cell lung cancer.In lung adenocarcinoma patients,CHD1 L could promote tumor invasiveness and metastasis.2.CHD1 L could predict poor prognosis in adenocarcinoma patients under 60 years old.3.In lung adenocarcinoma,CHD1 L may contribute to the invasiveness and metastasis through EMT by up-regulating SPOCK1 in non-small-cell lung cancer.Our results suggested that CHD1 L may be used as a target gene in the clinical treatment of lung adenocarcinoma.