Significance Of SIRT1Expression In Breast Cancer With Diabetes Mellitus

Diabetes has become endangered the third diseases of human healthand secondary to malignant tumor, cardiovascular and cerebrovasculardiseases. Epidemiological data show, with diabetes in Asian populationscompared with people without diabetes, the risk of cancer was significantlyincreased[1]. In the United States control study of breast cancer cases of Asianwomen, it found that women with a history of diabetes increase of68%risk ofbreast cancer,and the longer history of diabetes, increased risk higher. SIRT1(Sirtuin type1) is dependent on nicotinamide adenine dinucleotide (NAD~+)group Protein deacetylase involved in the covalent modification of histones,participate in histone modification，covalent cell proliferation, differentiation,metabolism, aging and apoptosis closely related. In normal cells, SIRT1is avery important anti-aging, antioxidant metabolism diseases protein. In tumorcells, it is SIRT1anti-apoptosis effect, the mutant cells can evade apoptosisand senescence control, and contribute to tumorigenesis. Some scholarsbelieve that women suffering from hormone-dependent tumors (egendometrial cancer, breast cancer), impaired glucose tolerance, insulinresistance significantly.When the Sirtl gene silencing or inhibition leads todownregulation of Sirtl protein,it can induce insulin resistance (IR), toincrease the expression of SIRT1especially in the case of IR, it can increaseinsulin sensitivity, promote insulin secretion, decrease plasma glucose levels,and improve insulin resistance, therefore it likely to become a researchpotential new target point on diabetes and tumors.Objective:To study expression of SIRT1in breast cancer with diabetes mellitus，toexplore the correlation between SIRT1and clinicopathologic features. toresearch its relation to type2diabetes mellitus and to assessed clinical value. Method：1189cases of female breast cancer patients underwent surgery werecome from the Baoding Central Hospital in January2007to January2011.,screened from30cases of breast cancer patients with type2diabetes,and30cases of cancer patients withoutdiabetes, in the same period as thecontrol group. All breast cancer patients before surgery were not carried outcancer treatment, were confirmed by pathological examination after surgeryconfirmed primary breast cancer.2To collected the complete clinical data of30cases of type2diabetesmellitus patients with breast cancer，including age, height, weight, TNM stage,clinical stage, histological grade and immunohistochemical pathology report(such as of p53、ER, PR, Her-2and other indicators), and do a complete record3Immunohistochemistry was carried out to examine the expression ofSIRT1in30breast cancer with diabetes mellitus and30breast cancer withnon-diabetic. The data were analyzed by using SPSS17.0statistical software,count data using2test, Correlation using Spearman correlation analysis，with P<0.05for the difference was statistical significant.Result：1The positive rate of SIRT1in breast cancer tissue with diabetes mellituswas significantly lower than that breast cancer tissue with non-diabetic（P<0.05）.2In SIRT1positive tissue, expression of p53and Her-2positive tissuewas significantly higher than that SIRT1negative tissue. the expression ofSIRT1is significantly positively related to p53and expression in breast cancertissue with diabetes（P<0.05）. ER and PR expression in SIRT1positiveorganization and SIRT1negative organization, the difference was notstatistically significant (P>0.05）.3The expression of SIRT1was positively correlated with the number oflymph node（P=0.011）and pTNM tumor stage（P=0.028）in breast cancer withtype2diabetes mellitus group. They was no correlation among age, BMI,tumor size, histological grade (P>0.05).The expression level of SIRT1was in lymph node-positive group was higher than that in lymph node-negative group（P<0.05）.Conclusions：1SIRT1was up-regulated in breast cancer, but the positive rate of SIRT1in breast cancer tissue with diabetes mellitus was significantly lower than thatbreast cancer tissue with non-diabetic, and was associated with the progressionof diabetes mellitus.2SIRT1protein was significantly positively correlated to p53、Her-2expression and clinicopathologic features such as number of lymph node andpTNM tumor stage, SIRT1may be a novel biological parameter to evaluatethe malognant degree of breast carcinoma and to predict prognosis of breastcancer.