RASA1 Expression And Clinical Significance In Non-small Cell Lung Cancer

Lung cancer is one of the most common malignant tumors and the leading causes of death.Recent years,the incidence of lung cancer showed a keeping rising trend in the world.The incidence of lung cancer has been at the first place in male malignant tumors in the developed countries of Europe and America and a lot of industrial cities in China.And it is also rapidly increasing,has been at the second or third place in women malignant tumors.Non-small cell lung cancer(NSCLC)accounts for more than 80% in lung cancer.Therefor,the research on NSCLC has very important practical significance.RAS gene mutations are consisting in approximately 30% of patients with lung adenocarcinoma.RAS p21 protein activator 1(RASA1)is one of RAS GTPase activating protein(RAS GAPs)family—which can activating GTP enzyme,making the activated RAS protein translate into non-activated state,so that terminate the transfer of signaling molecules,and supressor tumorigenesis.Based on findings to date,the expression level of RASA1 was decreased in different degree in a variety of human tumors,and have related with the anti-proliferation of lung squamous cell carcinoma.Objective: To investigate the expression of RASA1 in NSCLC tissues and adjacent normal tissues,and combined with clincal data,discussing its clinical significance and the correlation between RASA1 expression and clinicopathological features of NSCLC tumor size,histological type,lymph node metastasis and clinical stage.Method: Collected the surgery lung tissue specimens which diagnosed with non-small cell lung cancer by two independent pathlologists in First Affiliated Hospital of Yangtze University from March 2013 to January 2016.Sclected 202 cases of NSCLC specimens which meet the inclusive criteria as the expermental group,60 cases of adjacent normal lung tissue were randly from 202 cases as a control group,collected patients' pathology and clinical data such as sex,age,histological type,tissue differentiation,lymph node metastasis and the clinical stage.All the specimens were fixed with 4% paraformaldehyde and embedded in paraffin.Under the guidance of pathology experts,selected the representative diseased region to make the tissue microarray.The expression of RASA1 in 202 cases of NSCLC tissues and 60 cases of adjacent normal bronchial mucosa tissues were detected by tissue microarray and immunohistochemistry(immunohistochemistry,IHC)SP.RASA1 protein was located in cytoplasm.Cytoplasmic positive staining is yellow,brown yellow or brown.The judgement standard of immunohistochemistry SP detected RASA1 protein according to Xing is random observation five high-power field,calculate the average,each vision counting 100 cells,based on the percentage of tumor cells positive cells accounted divided into: ?25% for 1 point,25%~50% for 2 points,>50% for 3 points,no positive cytoplasmic staining for 0 points,combination with the stain of cytoplasmic,1 point cytoplasmic staining yellow,brown yellow cytoplasmic staining of 2 points,brown cytoplasmic staining for 3 points.Multiplication of two scores,more than 3 points was judged positive.All data were analyzed by statistical software SPSS18.0.Application chi-square test,correction for continuity chi-square test and continous calibration Fisher exact test to analysis the relationship between the expression of RASA1 in different tissures and its clinicopathological features,with P<0.05 was condidered statiscally significant.Result: The high express rate of RASA1 in non-small cell lung cancer was 74.8%(151/202),the high express rate of RASA1 in adjacent normal bronchial mucosa was 93.3%(56/60),the difference was statistically significant(P=0.002).The high express rate of RASA1 in lung adenocarcinoma tissue was 62.7%(64/102),the high express rate of RASA1 in lung squamous cell carcinoma was 85.6%(77/90)and the high express rate in other tissue types was 100%(10/10),the expression of RASA1 in lung adenocarcinoma was lower than that in lung squamous cell carcinoma and other types of NSCLC tissues and the difference was statistically significant(P<0.001).The high express rate of RASA1 in males NSCLC patients was 73.7%(115/156),but the high express rate of RASA1 in females NSCLC patients was 78.3%(36/46).The was no significantly difference of the expression rate of RASA1 between males and females NSCLC patients(P>0.05).The high expression rate of RASA1 in NSCLC patients with lymph node metastasis was 76.5%(65/85),the high expression rate of RASA1 in NSCLC patients without lymph node metastasis was 73.5%(86/117),the expression rate of RASA1 in NSCLC patients with lymph node metastasis was lower than that in females NSCLC patients,but there was no significantly difference(P > 0.05).According to the different clinical stages of NSCLC patients,the high expression rate of RASA1 in the low stage group(I/II)was 75%(123/164),the high expression rate of RASA1 in the high stage group(III/IV)was 73.3%(28/38).The expression rate of RASA1 in NSCLC patients in the low stage group was higher than that in high stage group,but there was no significantly difference(P>0.05).Conclusion: There was no correlation with age,sex,lymph node metastasis,clinical stage and the expression level of RASA1 in NSCLC tissues.The expression level of RASA1 gene in NSCLC tissues was significantly lower than that in normal bronchial mucosa adjacent to carcinoma.It is suggested that RASA1 play an important role in occurrence and development of NSCLC.The expression level of RASA1 in lung adenocarcinoma tissue was significantly lower than that in lung squamous cell carcinoma tissue and other non adenocarcinoma histological types of NSCLC tissue.The expression of RASA1 showed a significantly difference in different histological types of NSCLC tissue.