Clinical Significance Of Expressions Of ERCC1, EGFR And K-ras In Postoperative Treatment Of NSCLC

Objective:This study was conducted to investigate the relationship between the expressions of ERCC1 (excision repair cross-complementing group 1), EGFR (epidermal growth factor receptor) and K-ras and clinical biological characteristics of patients with NSCLC (non-small cell lung cancer) and to study the correlations among the expressions of ERCC1, EGFR and K-ras by analyzing the expressions of ERCC1, EGFR and K-ras in tumor tissues and adjacent tissues of patients with NSCLC. It was also discussed that the expressions of ERCC1, EGFR and K-ras could predict and estimate chemotherapy efficacy and prognosis of patients with NSCLC.Methods:97 cases were selected from Department of Thoracic Surgery of the Affiliated Hospital of Chengde Medical College during the period from June 2008 to December 2010. All cases were classified into two groups, chemotherapy group, including 50 cases undergoing four therapeutic courses of cisplatin-based chemotherapy, and non-chemotherapy group, including 47 cases. The method of MaxVision immunohistochemical staining was employed to analyze the expressions of ERCC1, EGFR and K-ras in tumor tissues of 97 patients and in adjacent tissues of 30 control group patients, randomly selected from the 97 patients. Postoperative follow-up was conducted to observe the survival of all patients. SPSS 17.0 was used in all statistical analyses. Chi-square test and exact probability analysis were employed to analyze the relationship between the expressions of ERCC1, EGFR and K-ras and clinical biological characteristics (gender, age, smoking index, differentiation degree, TNM stage, pathological type, etc.) of patients with NSCLC. Partitions of x2 method was used to study the differences of randomly two groups when had a significance result by Chi-square tests. Spearman rank correlation analysis was used to estimate the correlation among expressions of ERCC1, EGFR and K-ras. Kaplan-Meier survival curves were used to analyze the relationship between the expressions of ERCC1, EGFR and K-ras and overall survival (OS) of patients with NSCLC Log-rank test was used to compare the survival rates and overall survival time of chemotherapy group with that of non-chemotherapy group. Cox Proportional Hazard Model was used to evaluate factors influencing patients’ prognosis. The difference is statistically significant if P<0.05.Results:1. The positive expression rates of ERCC1, EGFR, K-ras in tumor tissues were 29.9%(29/97),22.7%(22/97) and 32%(31/97) respectively. In control group, the positive expression rate of EGFR in adjacent tissues was 3.3% (1/30), and negative expressions of ERCC1 and K-ras were noted in adjacent tissues. The difference was statistically significant in expressions of ERCC1, EGFR and K-ras between tumor tissues and adjacent tissues (P<0.05).2. There was no correlation between the expression of ERCC1 and gender, age, smoking index, differentiation degree, TNM stage and pathological type of NSCLC patients (P>0.05). The expression of EGFR had no correlation with NSCLC patients’age, smoking index, differentiation degree and TNM stage (P>0.05), while had significant correlation with patients’gender and pathological type (P<0.05). There was no significant difference in EGFR expression between adenocarcinoma and squamous cell carcinoma patients (corrected.P>0.0125). There were 7 female lung adenocarcinoma patients with positive expression of EGFR and 11 female patients with negative expression, while 4 male patients with positive expression and 7 male patients with negative expression. There was no statistically significance in positive expression of EGFR between male and female adenocarcinoma patients (P>0.05). The expression of K-ras had no correlation with patients’gender, age, differentiation degree and TNM stage (P>0.05), while had significant correlation with patients’smoking index and pathological type (P<0.05). There was no significant difference in K-ras expression between adenocarcinoma and squamous cell carcinoma patients (corrected P>0.0125). There was no correlation between ERCC1 and EGFR, as well as ERCC1 and K-ras, while there was negative correlation between EGFR and K-ras (r=-0.371, P<0.001).3. The one-year, two-year and three-year OS rates of NSCLC patients were 89.7%,59.4% and 44.8% respectively. Kaplan-Meier survival curves revealed that the survival time of patients with positive expression of ERCC1 was shorter than patients with negative expression of ERCC1 in chemotherapy group (P>0.05), while the survival time of patients with positive expression of ERCC1 was longer in non-chemotherapy group (P<0.05). In chemotherapy group, the survival time of patients with positive expression of EGFR and negative expression of K-ras was longer than patients with negative expression of EGFR and positive expression of K-ras, so was the case with non-chemotherapy group. Therefore, whether patients underwent chemotherapy or not, the survival time of patients with positive expression of EGFR and negative expression of K-ras was longer than patients with the negative expression of EGFR and positive expression of K-ras. Log-rank test was used in univariate analysis of patients’OS. It was revealed that OS was related with TNM stage (P<0.05), lymph-node metastasis (P<0.05), and K-ras expression (P<0.05), and that there was no statistical significance in survival rates of patients between chemotherapy and non-chemotherapy group (P>0.05). Cox proportional hazards multivariate analysis revealed that the expression of K-ras (RR:2.504,95%CI:1.317 to 4.760 P<0.05) and lymph-node metastasis (RR:4.055,95%CI:1.957 to 8.401 P<0.05) were independent factors influencing patients’OS.Conclusion:1. The positive expression rates of ERCC1, EGFR and K-ras in tumor tissues in trial group were all higher than that in control group.2. There was no correlation between the expression of ERCC1 in tumor tissues and the clinical biological characteristics of NSCLC patients. The expression rate of EGFR was higher in female adenocarcinoma patients, but was not significantly higher than male adenocarcinoma patients. The expression rate of EGFR in adenocarcinoma patients was not significantly higher than that in squamous cell carcinoma patients. The expression rate of K-ras was higher in patients with smoking adenocarcinoma, especially with bronchioloalveolar carcinoma, but was not significantly higher than that in patients with squamous cell carcinoma.3. There was negative correlation between the expressions of EGFR and K-ras in tumor tissues of NSCLC patients. In both chemotherapy and non-chemotherapy group, the survival time of patients with positive expression of EGFR and negative expression of K-ras was longer than that of patients with negative expression of EGFR and positive expression of K-ras.4. Patients with negative expression of ERCC1 might benefit from postoperative adjuvant cisplatin-based chemotherapy. Patients with high expression of ERCC1 had poor survival condition, resulting from resistance to chemotherapeutic agents (cisplatin:DDP). For platinum-resistant patients with high expression of ERCC1, especially patients with adenocarcinoma, the protein expression levels of EGFR and K-ras should be analyzed to select molecular targeted therapy, EGFR-TKI. However, in non-chemotherapy group, the survival time of patients with positive expression of ERCC 1 was longer than patients with negative expression of ERCC 1.5. The one-year, two-year and three-year OS rates of NSCLC patients were 89.7%,59.4% and 44.8% respectively. The results of log-rank tests revealed that there was no statistical significance in survival rates of patients between chemotherapy and non-chemotherapy group. The expression level of K-ras and lymph-node metastasis were independent factors influencing postoperative prognosis in patients with NSCLC...