| The worldwide morbidity and mortality of lung cancer is increasing yearby year, especially non-small cell lung cancer has become the main factor ofmalignant lung cancer mortality. According to global cancer statistics from2000to2005, male lung cancer incidence rate increased by14%and female by19.9%.Lung cancer patients would increase dramatically and would reach onemillion in the next20years. At present, diagnosis of lung cancer is based ontraditional diagnostic methods such as chest radiography, lung CT,bronchoscopy et al. which are not ideal for the early diagnosis. Most patientsare diagnosed at the advanced stage of lung cancer when missed optimumtiming of surgery. Thus，it is particularly necessary to find indicators of earlydiagnosis and effective early therapeutic targets of lung cancer.CREB is a transcription factor in the nucleus of eukaryotic, one of thetranscription factors of leucine zipper family. As a transcription factor，CREBcan regulate the transcription of multiple genes by the form of autophosphory-lation, plays a wide range of biological roles. And more attentions are given tothe CREB on the gene regulations of tumor cell growth, proliferation,differentiation, and apoptosis. It has been reported that CREB is associate withneoplastic diseases such as leukemia, melanoma, breast cancer. In both genemouse animal model of lung cancer and lung adenocarcinoma cell line A549,the insulin-like growth factor II (IGF-II) is found which active CREBphosphorylation through the cell signaling pathways, thereby promotsproliferation of tumor cells and inhibits apoptosis. Though still can not definethe mechanism of interaction between CREB and lung cancer, results amonganimal models and vitro induction of lung tissue experiment shows that there is sufficient reason to assume CREB over-expression and its phosphorylationlevel play an important role in lung cancer development.In this study, proteinimprinting technology (Western Blotting) is used to quantitative analysis of theCREB/p-CREB expression in61surgically resected non-small cell lungcarcinoma and adjacent normal tissue. Based on clinical information andfollow-up record, search the relationship between CREB/p-CREB expressionand NSCLC tissues, explore the clinical significance of the CREB/p-CREB inNSCLC.Sixty-one cases of fresh frozen specimens of non-small cell lung carcin-oma and adjacent tissue samples used in this experiment were taken frompatients in the Jilin University Bethune First Hospital of Thoracic Surgery whounderwent surgery in January2008to December2010, with complete clinicaldata, no preoperative radiotherapy or chemotherapy, and postoperativepathology clarified. After Protein quantitation by Western Blotting, SPSS19.0is used for statistical analysis relations between expression of CREB/p-CREBin different gender, age, smoking history, pathological type, histological grade,T stage, UICC stage. T test or t′test is performed, P <0.05indicates statisti-cally significant difference. According to follow-up, Cox regression model isperformed to analyze the prognostic factors of patients with NSCLC.The results shows that the CREB/p-CREB expression in NSCLC tissues(1.140±0.207,1.609±0.280) are higher than their adjacent tissues (0.591±0.291,0.927±0.236), also in squamous cell carcinoma (1.200±0.197,1.774±0.226) and adenocarcinoma (1.042±0.189,1.386±0.211) are higher than itsadjacent tissues, indicates the expression and phosphorylation of CREB inNSCLC are closely related to occurrence and development of both squamouscell carcinoma and adenocarcinoma。Expression in Paraneoplastic tissues andNSCLC tissues of p-CREB (0.927±0.236,1.609±0.280) is higher than that ofCREB level (0.591±0.291,1.140±.207), with statistically significant difference (P=0.000, P=0.000),indicates CREB is in a active state inParaneoplastic tissues and NSCLC tissues. There is no statistical differencebetween the CREB/p-CREB expression in the adjacent tissue of squamouscell carcinoma (0.573±0.268,0.943±0.193) and adenocarcinoma (0.621±0.329,0.901±0.298)(P=0.617, P=0.540), but the expression of squamouscell carcinoma of CREB/p-CREB (1.200±0.197,1.774±0.226) were higherthan adenocarcinoma (1.042±0.189,1.386±0.211), with statisticallysignificant difference(P=0.003, P=0.000),which probably imply thedifference of upstream signaling pathway of CREB transcription factorbetween occurrence, development of the squamous cell carcinoma andadenocarcinoma, indicate CREB transcription play a more important role in thedevelopment process of squamous cell carcinoma. It has been reported thatCREB expression and phosphorylation level is higher in smokers thannon-smokers. In this study, there is no statistical significance (P=0.831)difference between the the smoking group CREB expression (1.137±0.196)and non-smoking group (1.149±0.236), which is inconsistent with the formerreport, may attribute to statisticall discrepancy. However, the smoking group inp-CREB expression (1.664±0.272) was significantly higher than non-smokinggroup (1.487±0.264), with statisticall significant difference (P=0.021),indicate p-CREB expression associate with mechanism of smoking leads lungcancer.CREB/p-CREB expression is irrelevant to patient gender (P=0.580, P=0.988), age (P=0.632, P=0.751), T stage (P=0.183, P=0.895), N-stage (inNSCLCP=0.372, P=0.265), UICC stage (P=0.278, P=0.332), histologicalgrade (P=0.504, P=0.541). COX regression analysis shows patient’s gender,age, tumor type, stage, histological grade, CREB/p-CREB expression werenot relevant to prognosis (P>0.05). |
