The Expression And Clinical Significance Of Serum CREB In Non-small-cell Lung Cancer Patients

Objective: As a transcription factor within the nucleus, CREB mainly regulatestranscription by auto-phosphorylation for the cAMP signal response. In recent studies,CREB plays an important role in cell growth, differentiation and proliferation through itsregulation on related genes of a wide range of inflammation and proliferation. CREBphosphorylation is likely to be an essential factor in various carcinogenic factors causesexcessive tumor cell growth, differentiation and inhibition of tumor cell apoptosis. Thesustained activation of CREB is closely related to development of lung cancer, and it mightbe an important target for future treatment of lung cancer. There have been several studiesfor non-small cell lung cancer patients with CREB and its phosphorylation focused on thelung cancer cell lines and tissue samples of lung cancer, but the relationship between serumCREB content level and NSCLC has not been reported. In this study, we examined thequantitative expression of CREB in normal adult serum and the patients with different typesof non-small-cell lung cancer by enzyme-linked immunosorbent assay test, which combinedwith clinical and follow-up data to explore the law of its quantitative changes and the valuefor NSCLC diagnosis and differentiation.Methods: The serum of64cases of NSCLC patients was taken from the thoracicsurgery department of the First Hospital of Jilin University. All of the cases had completelyclinical data and underwent surgery between Jan.2008and Dec.2010. The collection ofclinical data included gender, age, smoking history, case diagnosis, TNM stage, and UICCstage. The serum of64normal healthy cases was taken from in the First Hospital of JilinUniversity medical center correspondently. There were41cases of NSCLC male and23cases of female with the average age of59.7±7.8years, among which has43formersmokers.20cases of phase I,27cases of phase II and17of phase III cases in NSCLC groupwere staged according to the1997International Union Against Cancer. There were35casesin squamous cell carcinoma,18cases in adenocarcinoma and11cases in mixed carcinoma(adenosquamous carcinoma or squamous carcinoma).23cases were poorly differentiated,39cases were moderately differentiated and two cases were well-differentiated. Lymph nodemetastasis was found in33cases. In the healthy group, there were40cases of men and24cases of women, whose average age of60.0±8.0years. The deadline of follow-up was on November14,2011. After the test by enzyme-linked immunosorbent assay (ELISA),quantitative analyses between groups were examined by t-test, and the factors that affectingthe prognosis of NSCLC patient were analyzed by Cox regression method. The receiveroperating curve was utilized to determine the cutoff value of serum CREB and p-CREB ofincluded groups, which were selected according to the t-test results that statisticallysignificant difference. P<0.05indicated a statistically significant differenceResults: Expression levels of serum CREB between normal healthy adults and patientswith NSCLC were basically the same, while the level of serum p-CREB NSCLC patientswas significantly higher than that of normal healthy population (0.399±0.242ng/ml vs.0.058±0.008ng/ml, P=0.000). The level of serum CREB in healthy human was higher thanthe level of p-CREB (0.099±0.058ng/ml vs.0.058±0.008ng/ml, P=0.000), which wasjust opposite of the result in NSCLC patients (0.122±0.113ng/ml vs0.399±0.242ng/ml, P=0.000). Expression level of serum p-CREB in female patients was higher than that of malepatients (0.488±0.257ng/ml vs.0.354±0.225ng/ml, P=0.044). Expression level of serumCREB in squamous cell carcinoma was higher than that of lung adenocarcinoma (0.150±0.126ng/ml vs.0.084±0.080ng/ml, P=0.049). Expression level of serum p-CREB inpoorly differentiated lung cancer was higher than that of well-differentiated lung cancer(0.490±0.172ng/ml vs.361±0.262ng/ml, P=0.030). COX regression model analysisshowed that the age, gender, smoking history, type of NSCLC, differentiation, stage andserum CREB and p-CREB expression levels had no effect on the prognosis (P>0.05).Conclusion: CREB and p-CREB do express in the serum of patients with non-smallcell lung cancer. Expression level of serum p-CREB in NSCLC patients is higher thanhealthy population. Expression level of serum CREB in healthy population is higher than thep-CREB, while there is a reverse result in NSCLC patients. Expression level of serumsquamous cell carcinoma patients CREB is higher than that of adenocarcinoma patients.Expression level of serum p-CREB in female patients is higher than that of male patients.Expression level of serum p-CREB in poorly differentiated patients is higher than that ofwell-differentiated.