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Expression And Clinical Significance Of SIRT6 And Autophagy-related Proteins Beclin1 And LC3 In Gastric Cancer

Posted on:2020-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:H GuoFull Text:PDF
GTID:2404330596978529Subject:Oncology
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Introduction:Gastric cancer is currently one of the most common malignancies.Although the incidence and mortality of gastric cancer have shown an overall decline in the world,their morbidity and mortality are still among the top three in the world.In the United States,the mortality rate of gastric cancer in men has dropped from 28/100,000 to5.8/100,000.However,due to the large base,more than 100,000 Americans die each year because of stomach cancer,and more than 200,000 Americans per year.The new diagnosis is gastric cancer.There are still high morbidity and high mortality rates in individual countries and regions,including China,Japan,Chile and other regions.According to GLOBOCAN data in 2008,the number of new cases of gastric cancer in China accounted for 47%of the total number of cases in the world.Therefore,the diagnosis and treatment of gastric cancer is the focus of prevention and treatment of cancer in China.The main treatments for gastric cancer are surgery,chemotherapy,radiotherapy,etc.,and molecular targeted drugs are also being developed.Surgical resection of the tumor and peripheral lymph node dissection is the only cure,but surgery is only effective in early gastric cancer,gastric adenocarcinoma is relatively insensitive to radiotherapy,chemotherapy is only 30%-50%effective,current gastric cancer The treatment lacks a better method of treatment.The researchers found that changing some of the regulatory factors will change their corresponding signaling pathways,which will affect the development of tumors,so look for these possible regulatory factors of gastric cancer,explore its relationship with gastric cancer,may treat gastric cancer And prognosis has important clinical significance.Autophagy:The cell degrades the damaged protein or organelle under the pressure of itself or the external environment,and reuses the decomposed substance to maintain the internal environment stability of the cell.Tumors are closely related to the occurrence and development of autophagy,and autophagy plays different roles in different stages of tumor development.Beclin1 is a key protein initiated by autophagy,and LC3 is a key protein of autophagy effect,which plays an important role in autophagy,and it is observed that these two proteins inhibit tumor development.Silent Information Regulator 6(SIRT6)has the function of inhibiting most tumors,but it has a tumorigenic effect in a small number of tumors.It has been found that SIRT6regulates intracellular autophagy mainly through the IGF-Akt-mTOR pathway,reducing the accumulation of metabolic substances and cellular senescence.SIRT6 is the upstream regulatory molecule of the IGF signaling pathway,especially IGF1R.Studies have shown that the IGF1R-Akt-mTOR signaling pathway can regulate the level of autophagy and affect the occurrence of disease.However,whether SIRT6 can influence the occurrence and development of tumors through this signaling pathway is not clear.At present,whether SIRT6 and autophagy work together to cause gastric cancer has not been clearly studied,which is also the focus of current research.Through the preliminary proven SIRT6,Beclin1 and LC3 expression in gastric cancer cells,and the relationship between the pathology parameters and the relationship between the three indicators,preliminary the relationship between these indexes and gastric cancer development,can provide the basis for subsequent molecular level and direction,are more likely to diagnosis and treatment of gastric cancer provide new molecular markers and therapeutic targets.Aims:The expressions of SIRT6,Beclin1 and LC3 in the normal tissues,adjacent tissues and gastric cancer tissues of the same patients were observed.The expressions of SIRT6,Beclin1 and LC3 and the clinicopathological parameters of gastric cancer including age,sex,and The relationship between tumor size,tumor differentiation,tumor stage and lymph node metastasis clearly determines whether SIRT6 interacts with autophagy and plays a role in the development of gastric cancer.Methods:Immunohistochemistry was used to observe the expression of SIRT6,Beclin1 and LC3 in 72 normal tissues,adjacent tissues and gastric cancer tissues.Spearman test was used to analyze whether the expression of SIRT6 and Beclin1 or LC3 was correlated.?~2and Fisher The exact test analysis of SIRT6,Beclin1,LC3 expression and clinical pathological parameters of gastric cancer including patient age,gender,tumor size,tumor differentiation,tumor stage and whether there is lymph node metastasis.Results:1.The positive expression rates of SIRT6 in gastric cancer,adjacent normal tissues and normal tissues were 56.94%(41/72),73.61%(53/72)and 77.78%(56/72),respectively.The positive expression rate in tissues was significantly lower than that in adjacent normal tissues(p<0.05).There was no significant difference in the expression of SIRT6 between adjacent tissues and normal tissues(p>0.05);Beclin1 was in gastric cancer and cancer.The positive expression rates of paracrine and normal tissues were30.56%(22/72),48.61%(35/72)and 63.89%(66/72),respectively.The positive expression rate of Beclin1 in gastric cancer tissues was significant.Below the adjacent normal tissues and normal tissues(p<0.05),the expression of Beclin1 in adjacent tissues and normal tissues was not statistically significant(p>0.05);the positive expression of LC3 in gastric cancer,adjacent tissues and normal tissues.The rates were 29.17%(21/72),51.39%(37/72)and 65.28%(47/72).The positive expression rate of LC3 in gastric cancer tissues was significantly lower than that in adjacent normal and normal stomach.There was no significant difference in the expression of LC3 between adjacent tissues and normal tissues(p>0.05).2.There was a significant positive correlation between the expression of SIRT6 and the expression of Beclin1 or LC3 in gastric cancer tissues(p<0.05).3.The expressions of SIRT6,Beclin1 and LC3 were not significantly correlated with age,sex and tumor location of gastric cancer patients(p>0.05).The expressions of SIRT6,Beclin1 and LC3 were significantly correlated with tumor stage,differentiation degree and lymph node metastasis.(p<0.05).Conclusions:1.The expression of SIRT6 and autophagy-related proteins Beclin1 and LC3 were significantly decreased in gastric cancer tissues.2.There is a significant positive correlation between the expression of SIRT6 and the expression of Beclin1 or LC3 in gastric cancer tissues.3.The expressions of SIRT6,Beclin1 and LC3 were not significantly correlated with age,gender and tumor location of gastric cancer patients,but were significantly correlated with tumor stage,differentiation degree and lymph node metastasis.
Keywords/Search Tags:autophagy, SIRT6, Beclin1, LC3, gastric cancer, immunohistochemistry
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