Expressions And Clinical Significances Of EGFR、KRAS、BRAF And C-Met Proteins In Non Small Cell Lung Cancer

Objective:Lung cancer is the most common fatal disease, non small cell lung cancer(NSCLC) accounts80%of it. Although the surgical resection has been the most useful treatment for the NSCLC patients, there are many patients needing adjuvant chemotherapy. Moreover there are many patients who lost the opportunity to receive the surgical resection due to the disease in advanced stage diagnosed, the chemotherapy has become a main treatment method. However, the chemotherapy lacks specificity for the cancer cells and often has many side effects. Recently, the personalized therapy, particularly the molecular target therapy has been applied for NSCLC and receives much attention.Tyrosine kinase inhibitor(TKI), a represent of molecular target drugs, has succeed in treating the NSCLC patients whose cancer brought epidermal growth factor receptor(EGFR) with some exon mutations. However, many patients could not get benefit from EGFR-TKI because of the drug resistances. The reasons of drug resistances were thought to be the mutations of EGFR, downstream key molecular mutations of the EGFR signal pathways as KRAS, BRAF, other signal pathways as c-Met activated and epithelial-mesenchymal transition of the carcinoma cells.It was reported that there were about50%NSCLC patients with secondary drug resistances of EGFR-TKI bringing the mutation of EGFR exon20. The activated mutations of KRAS and BRAF were often found in the carcinoma cells of NSCLC, these mutant proteins independently promoted the cells to proliferate whether EGFR inhabited or not. About20%secondary drug resistances of EGFR-TKI in NSCLC would be related to the mutation of c-Met.The activated c-Met would regulate the proliferation and differentiation of the cells though MAPK or PI3K signal pathways. Detection of the protein expressions of EGFR, KRAS, BRAF and c-Met would be helpful for selecting patients who would benefit from EGFR-TKI.Methods:Immunohistochernistry was used to detect EGFR, KRAS, BRAF and c-Met protein expressions in80samples of NSCLC tumor tissues and50samples of their surrounding tissues.The software SPSS was used to analyze the correlations of these protein expressions to patients’clinical pathological agents and the correlations among these protein expressions.Results:EGFR protein expression positive rates in NSCLC and their surrounding tissues were45.0%and60.0%respectively, there was no significant difference between them (P>0.05). In the same case, EGFR protein expression in the tissues surrounding the carcinomas was positively correlated to that in carcinomas significantly (r=0.294, P<0.05). There were no significant correlations of EGFR protein expression to patients’gender, age and smoking history, as well as carcinoma lymph node metastasis, pathological type and differentiation (P>0.05).KRAS protein positive expression rates in NSCLC and their surrounding tissues were40.0%and42.0%respectively, there was no significant difference between them (P>0.05). In the same case, KRAS protein expression in the tissues surrounding the carcinomas was positively correlated to that in carcinomas significantly (r=0.455, P<0.05). There was no significant correlations of KRAS protein expression to patients’gender, age and smoking history, as well as carcinoma lymph node metastasis, pathological type and differentiation (P>0.05).BRAF protein expression positive rates in NSCLC and their surrounding tissues were26.3%and26.0%respectively, there was no significant difference between them (P>0.05). In the same case, BRAF protein expression in the tissues surrounding the carcinomas was positively correlated to that in the carcinomas significantly (r=0.078, P>0.05). In NSCLC, the positive rates of BRAF protein in smokers and nonsmokers were12.2%and33.2%respectively, there was significant difference between them (P<0.05); the rates in the patients with lymph node metastasis and without were12.7%and40.3%respectively, there was significant difference between them (P<0.05); the rates in high differentiation group and low differentiation group of squamous cell carcinoma were10.5%and42.9%respectively, there was significant difference between them (P<0.05). There was no significant correlations of BRAF protein expression to patients’gender and age (P>0.05). c-Met protein expression positive rates in NSCLC and their surrounding tissues were70.0%and24.0%respectively, there was significant difference between them (P<0.01). In the same case, c-Met protein expression in the tissues surrounding the carcinomas was positively correlated to the carcinomas significantly (r=0.293, P<0.05). In NSCLC, the positive rates of c-Met protein in the patients with lymph node metastasis and without were82.0%and59.0%respectively, there was significant difference between them (P<0.01). There was no significant correlations of c-Met protein expression to patients’gender, age and smoking history, as well as carcinoma pathological type and differentiation (P>0.05).In NSCLC, the protein expression of EGFR had no significant correlations to those of KRAS (r=0.077, P>0.05), BRAF(r=0.067, P>0.05) and c-Met (r=0.099, P>0.05). The protein expression of KRAS had no significant correlations to those of BRAF (r=0.200, P>0.05) and c-Met (r=0.110, P>0.05). The protein expression of BRAF had no significant correlation to that of c-Met (r=0.087, P>0.05).Conclusion:1, The EGFR, KRAS and c-Met proteins express in NSCLC as well as in their surrounding tissues.2, The poorly differentiated squamous cell carcinoma of NSCLC without lymph node metastasis in non smokers would likely to express BRAF protein.3, c-Met protein expression would related to lymph node metastasis of NSCLC.4, Detection of EGFR, KRAS, BRAF and c-Met protein expressions might be helpful to select patients who could get benefit from EGFR-TKI...