The Clinical Significance And Correlation Between CREPT And Cyclin D In NSCLC Tissues

Objective:To detect the expression of CREPT and Cyclin Ds in non-small cell lung carcinoma and paired normal tissues and analyze the differences and correlation between CREPT and Cyclin Ds. And to explore the function and clinical significance of CREPT and Cyclin Ds in NSCLC. Methods:To detect CREPT and Cyclin Ds expression in both NSCLC and paired carcinoma tissue that collected from 271 NSCLC patients by immunohistochemistry, Western Blot and PCR. Results:1. The positive rate of CREPT was 96.1% in NSCLC and 30.4% in the paired normal tissues, the difference was significant(P=0.000). The expression of CREPT had no difference statistically either in different ages of patients(P=0.380), gender(P=0.627), smoking history(P=0.894), tumor sizes(P=0.253) or types(P=0.638).The differences were significant in different pathological grade of NSCLC,(P=0.000).In different clinical stages of NSCLC, the differences were significant(P=0.025), but data showed no difference in squamous carcinoma and adenocarcinoma; the expression of CREPT had significant difference between lymph node metastasis groups and non-metastasis groups(P=0.003) except in squamous carcinoma groups(P=0.166). The Kaplan-Meier analysis and a log-rank test showed that the positive CREPT expression is associated with decreased overall survival significantly(P<0.01). The multivariate analysis revealed the positive CREPT expression is associated with decreased overall survival. The adjusted HR was1.367(95% CI:1.085,1.723,P<0.01), indicated that CREPT could be used as an independent prognostic factor. Western Blot and PCR also proved that the different expression of CREPT in non-small cell lung carcinoma and paired normal tissues.2. The expression of Cyclin D1、Cyclin D2、Cyclin D3、CDK4 in non-small cell lung carcinoma and paired normal tissues was significantly different(P=0.000); The expression of Cyclin D3、CDK4 in the groups of differentiated degree, different clinical TNM stage and that in groups of patients with/without lymph node metastasis were significantly different in NSCLC(P<0.01). The expression of Cyclin D2 in the groups of differentiated degree was a significant difference in NSCLC and adenocarcinoma(P<0.05). The expression of Cyclin D1 in squamous carcinoma was significantly different only in the groups of different clinical stage of adenocarcinoma.3. The expression of CREPT was not significantly associated with the expression of Cyclin D1( R=0.295)、Cyclin D2(R=0.338), but its expression was significantly associated with the expression of Cyclin D3(R=0.458)、CDK4(R=0.520) and Ki67(R=0.621)(P=0.000); The expression of CREPT was significantly associated with the expression of Cyclin D3、CDK4 and Ki67 in the group of poorly differentiated or the patient in III-IV stage(P<0.01). Conclusion:1. CREPT and Cyclin Ds are both over expressed in NSCLC tissues and they could distinguish tumor tissues from normal tissues.2. The expression of CREPT in the group of different clinical TNM stage and in the group with lymph node metastasis or not were all significant difference in NSCLC, these results indicated CREPT played critical roles during the development of NSCLC. Survival analysis showed that the expression of CREPT is closely related to the lifetime of the patients, which shows CREPT may be an independent prognostic marker.3. The expression of Cyclin D3 and CDK4 in the group of different clinical TNM stage and in patients with lymph node metastasis or not was all significantly different in NSCLC.4. Data showed that the expression of CREPT was not significantly associated with the expression of Cyclin D1、Cyclin D2, but its expression was significantly associated with the expression of Cyclin D3、CDK4 and Ki67 in the advanced NSCLC patients, indicating that CREPT may affect the progression of NSLCL by increasing the expression of Cyclin D3 and CDK4.