Expression And Clinical Significance Of SIRT3and HIF-1α Protein In Gastric Carcinoma

Gastric carcinoma is one of the common malignant tumors in digestivesystem, the number of gastric carcinoma in China is about50%of that in theworld. In recent years, although comprehensive treatment of gastric carcinomahas made great progress, incidence and mortality of gastric carcinoma have noobvious decline. Its invasion and metastasis are the main factors affecting theprognosis. Most studies show that the invasion and metastasis of gastriccarcinoma are a multi-gene, multi-factor and multi-stage progress. It is veryimportant to research gastric cancer-related genes and their protein products,which is not only for understanding the pathogenesis of gastric cancer but alsofor clinical molecular diagnosis and prognosis. Among the sirtuins located inthe mitochondria, SIRT3is a major mitochondrial deacetylase that targetsmany enzymes involved in the activation of many oxidative pathways andmaintain reactive oxygen species (ROS), which is involved in energymetabolic processes and responsible for aging, apoptosis, and tumorigenesis.SIRT3expression levels are not uniform in different tumors, and whetherSIRT3mediates cancer development as a tumor promoter or a tumorsuppressor remains controversial. Hypoxia inducible factor-1(HIF-1), atran-criptional complex, which generally resides in anoxic mammal andhuman cells, has already been identified as one critical protein directlyreacting to hypoxia. HIF-1is a heterodimer composed of HIF-1α and HIF-1βsubunits. HIF-1α is the only oxygen regulator subunit, which determines theactivity of HIF-1and activates transcription of genes encoding glucosetransporters, glycolytic enzymes, and angiogenesis. Some Research shows thedecease or loss of SIRT3can inhance HIF-1α expression in tumor tissue,butits specific mechanism was not clear. In this paper, we detected theexpressions of SIRT3and HIF-1α protein in gastric cancer to discuss theirbiological effects on development of gastric cancer and the correlationbetween them. The first part Expression and clinical significance of SIRT3in gastriccarcinomaObjective:By detecting the expressions of SIRT3protein in gastric carcinoma to researchwhether it is correlated with the clinic-pathological parameters of GC，todiscuss biological effects of SIRT3on development of GC.Method:Collecting80cases of paraffin specimens of gastric carcinoma tissue and50cases of paraffin specimens of normal gastric tissue(away the tumor morethan5centimetres) with which were surgically removed and certified in thefirst hospital of Qinhuangdao from January,2012to October,2013.Immunohistochemistry was carried out to detect the expression of SIRT3inthe gastric carcinoma and normal gastric tissue, to observe the expression ofSIRT3and analyse correlation combined the expression of SIRT3withclinic-pathological parameters.Collecting30cases of fresh gastric carcinoma tissue and adjacent normalnon-cancerous tissue(away the tumor more than5centimetres) which weresurgically removed and certified in the first hospital of Qinhuangdao fromJanuary,2013to October,2013. Western-blotting was carried out to detect thethe expression of SIRT3in the gastric carcinoma and normal gastric tissue.Result:1The immunohistochemical result: the positive expression rates ofSIRT3protein in gastric cancer is53.8%(43/80), the positive expression ratesof SIRT3protein in normal gastric tissue is86.0%(43/50). The expression ofSIRT3protein in carcinomatous gastric tissue is obviously lower than that innormal gastric tissue, the difference was statistically significant(P<0.05).2The relation between SIRT3protein and clinical date: the expression ofSIRT3showed significant relation with invasion depth, lymph node metastasis,TNM stage (P<0.05), and it was not related with the age, gender, tumor size,or differentiation status (P>0.05).3The western-blotting result: the expression of SIRT3protein(SIRT3/β-actin）in gastric carcinoma tissue (0.6551±0.3170) is lower than that in normal gastric tissue (0.8029±0.3290), the difference was statisticallysignificant (P<0.05).Conclusion：The expression of SIRT3is lower in gastric cancer than that in normalgastric tissue，which is negatively related with invasion depth, lymph nodemetastasis, TNM stage. SIRT3may inhibit the development of gastric cancer.The second part Expression and clinical significance of HIF-1α in gastriccarcinoma and the relationship between SIRT3and HIF-1αObjective:By detecting the expressions of HIF-1α protein in gastric carcinoma，toresearch whether it is correlated with the clinic-pathological parameters ofGC，to discuss biological effects of HIF-1α in the progress of GC development.To analysis whether there is relation between SIRT3and HIF-1α.Method:Immunohistochemistry was carried out to detect the expression ofHIF-1α in the gastric carcinoma and normal gastric tissue, to observe theexpression of HIF-1α and analyse correlation combined the expression ofHIF-1α with clinic-pathological parameters. Spearman rank correlationanalysis was carried out to discuss about relation between SIRT3and HIF-1α.Result:1The immunohistochemical result: the positive expression rates ofHIF-1α protein in carcinomatous gastric tissue is75%(60/80), The positiveexpression rates of HIF-1α protein in normal gastric tissue is zero. Theexpression of HIF-1α protein in carcinomatous gastric tissue is obviouslyhigher than that in normal gastric tissue, the difference was statisticallysignificant (P<0.05).2The relation between HIF-1α protein and clinical date: the expressionof HIF-1α showed significant relation with tumor size, invasion depth,lymph node metastasis and TNM stage (P<0.05), and it was not related withthe age, gender and differentiation status（P>0.05).3The correlation coefficient of SIRT3and HIF-1α is:r=-0.429(P<0.05).the expression of HIF-1α is negatively related with the SIRT3protein in Gastric cancer（P<0.05）.Conclusion：The expression of HIF-1α protein in carcinomatous gastric tissue ishigher than that in normal gastric tissue，which is significantly related withtumor size,invasion depth,Lymph node metastasis,TNM stage. HIF-1α maypromote the development of GC. the expression of HIF-1α is seeminglynegatively related with the SIRT3protein in GC.