Expression Of SIRT1 And Its Clinical Significance In Lung Adenocarcinoma

OBJECTIVE To investigate the expression of SIRT1 in lung adenocarcinoma and its correlation with clinicopathological characteristics, EGFR amplification and prognosis.METHODS The expression of SIRT1 was detected by immunohistochemistry(IHC) in tissue microarrays containing paired tumor and peritumoral tissues from 75 patients who had undergone resection for histologically confirmed lung adenocarcinoma.Epidermal growth factor receptor(EGFR) amplification were evaluated by fluorescent in situ hybridization(FISH). Chi-square test was utilized to analyze the relationship between SIRT1 expression and clinicopathological features or EGFR amplification. SIRT1 expression and clinicopathological characteristics in relation to postoperative prognosis was examined by Kaplan-Meier and Log-rank test.The Cox proportional hazards model was used to estimate hazard ratio(HR)with 95 % confidence interval(CI)between the different clinical characteristics,expression of SIRT1 and survival.RESUITS The SIRT1 expression level was higher in tumor tissues than in peritumoral tissues(the mean H-scores were 260 and 113 respectively,p<0.001).Pathological stage was significantly correlated with SIRT1 expression(p value was 0.029). However, no significant correlation was found between the SIRT1 expression and gender,age,lymph node invasion,distant metastasis, TNM stage or pathological subtype(p value was 0.232, 0.318, 0.377, 0.245, 1.000, 0.216, respectively).Significant correlation was found between lymph node invasion and EGFR amplification(P =0.004). However, gender,age, lymph node invasion,pathological stage,distant metastasis,TNM stage and pathological subtype are not significantly correlated with EGFR amplification( p value was 0.608, 0.274, 0.588, 0.275, 0.317,0.449). Both univariate and multivariate analyses demonstrated that high SIRT1 expression was a negative prognostic indicator of OS(HR=3.991,95%CI:1.411~11.288,p=0.009; HR=4.388,95%CI:1.192~16.155,p=0.026, respectively). EGFR amplification was not a prognostic indicator of OS(HR=1.452,95%CI:0.835~1.997,p=0.2446; HR=1.896,95%CI:0.505~3.726,p=0.443,respectively). SIRT1 expression is not significantly correlated with EGFR amplification(r=0.223,p=0.278).CONCLUSION Pathological stage of lung adenocarcinoma was significantly correlated with SIRT1 expression. High expression of SIRT1 was associated with poor prognosis in lung adenocarcinoma. SIRT1 expression was a prognostic indicator of OS. SIRT1 expression is not significantly correlated with EGFR amplification.