The Expressions Of C-Cbl,Cbl-b And EGFR In NSCLC And The Correlation With Prognosis

ObjectiveThe aim is to investigate Expressions of c-Cbl,Cbl-b and epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) and find the Correlation with clinicopathological characteristics and prognosis.MethodsFrom Feb 1997 to Sep 2000, NSCLC samples(n=94) were assembled in a tissue microarray, using immunohistochemical SP methods, which came from Department of Chest Surgery, The First Hospital of China Medical University and underwent radical operation of lung cancer. Construct the tissue microarray. We detect the expression of c-Cbl, Cbl-b, EGFR using the immunohistochemical SP method and analyse the relationship between c-Cbl, Cbl-b, EGFR in patients'characters and prognosis.ResultsIn 94 patients with non-small cell lung cancer specimens, the positive expression of EGFR, c-Cbl and Cbl-b was 60.64%(57/94),30.85% (29/94) and 84.04%(79/94), respectively. And the correlation between EGFR and c-Cbl, Cbl-b expression was no significant correlation (P= 0.931, P= 0.866), and the correlation between c-Cbl and Cbl-b was positive, (r= 0.435, P= 0.000). EGFR protein expression and gender (P= 0.042) have correlation, female non-small cell lung cancer EGFR positive rate was 80.95%(17/21) higher than in males 54.79%(40/73). EGFR protein expression shows no significant correlation with age, pathological type, TNM stage and lymph node metastasis, smoking history and other parameters. c-Cbl, Cbl-b protein expression show no significant correlation with gender, age, pathological type, TNM stage and lymph node metastasis, smoking history and other parameters. In the general population EGFR, c-Cbl, Cbl-b expression and survival in patients have no obvious correlation. There is a negative correlation trend (r=-0.192, P= 0.078) between c-Cbl protein expression and tumor size (T stage), but have no statistically significant. Subgroup analysis showed that in EGFR-positive patients, the Cbl-b high expression patients had better overall survival than Cbl-b lowe expression patients (P= 0.138). The overall survival of c-Cbl-positive patients was better than c-Cbl negative group, the median survival time of c-Cbl-negative patients was 38.1±4.1 months,95% CI [29.99,46.12], the median survival time of c-Cbl-positive patients was 59.7±5.8 months,95% CI [48.4,71.1]. The differences between the two group was statistically significantly (P= 0.014). COX multivariate analysis showed that tumor size, lymph node metastasis is an independent prognostic risk factor (P= 0.001,95% CI:[1.751-4.939], RR= 2.940; p= 0.001,95% CI:[1.425-4.219], RR=2.452)ConclusionsThe expression of EGFR protein is related with gender. In non-small cell lung cancer, the EGFR positive rate of female was higher than male. The expression of c-Cbl, Cbl-b have no correlation with gender, age, pathological type, TNM stage and lymph node metastasis, smoking history and other parameters. The expression c-Cbl protein is negatively related with tumor size (T stage).The patients with EGFR-positive and Cbl-b high expression patients had better overall survival than the patients with Cbl-b low expression patients. The total survival in the patients with c-Cbl-positive expression was better than the patients with c-Cbl-negative expression. We speculate that c-Cbl may inhibit tumor cell proliferation by inhibiting EGFR function or promoting the degradation of EGFR. But specific mechanisms to be further confirmed. Tumor size and lymph node metastasis are independent risk factors which affect prognosis.