Expression Of Hexokinase-2 In Gallbladder Cancer Cells And Its Clinical Significance

BackgroundThe incidence of gallbladder cancer in China ranks sixth in digestive tract cancers,and it is increasing year by year.It accounts for 80%-95% of biliary malignancies,and the median survival time is the shortest,and the 5-year survival rate is only 5%.And according to the different stage of disease development,the median survival time of gallbladder cancer patients is about 2-19 months.。In different parts of the world,different countries,the incidence of gallbladder cancer is not the same.The high incidence of gallbladder cancer is mainly in Japan,India,Poland,Chile and other countries。The geographical distribution of gallbladder cancer in China is also significantly different.Northeast and northwest regions are high incidence of gallbladder cancer.Gender differences are also more pronounced,with more women than men.But so far,the etiology and pathogenesis of gallbladder cancer is still not completely clear,and may be closely related to the occurrence of gallstones and cholecystitis.At present,the treatment of gallbladder cancer is mainly based on surgery,but the surgical approach and effect are closely related to the staging and pathological types of gallbladder cancer.Patients with advanced gallbladder cancer are often prone to loss of surgical opportunities or have poor postoperative outcomes that fall short of expectations.Other treatments,such as chemotherapy and radiotherapy,can only be used as adjunctive treatments.The effect is not ideal.Gallbladder cancer is more common in the middle-aged and elderly populations.Gallbladder stones and jaundice are frequently associated with the disease.Clinically,it often treats right upper abdominal pain.Gallbladder cancer has no specific clinical manifestations and symptoms,and it is not easy to diagnose early.If there is a combination of large gallstones or formation of cantonal stones,it can be characterized as recurrent episodes of right upper quadrant pain.When gallstones or gallbladder masses oppress or obstruct the bile duct,symptoms such as jaundice appear.Gallbladder cancer has a high degree of malignancy.When it is discovered clinically,it often enters the middle and late stages,and there may be progressively increased pain in the right upper quadrant.If the cancer has metastasized,it is often accompanied by pain at the metastatic site..Because the location of the gallbladder cancer is closer to the hepatic portal,the infiltration and metastasis of the liver and surrounding organs are more likely to occur,and the optimal surgical treatment time is lost,which affects the prognosis and survival of the patient..Therefore,we must strengthen the basic research on gallbladder cancer,hoping to improve the early diagnosis and treatment of gallbladder cancer.Although with the continuous deepening of clinical research and basic research,both the diagnosis of gallbladder cancer and the treatment of gallbladder cancer have made some progress,but there is still no special breakthrough.In particular,compared with other malignancies,the research on gallbladder cancer still lags behind.To increase the research on gallbladder cancer and increase the degree of attention to gallbladder cancer is still a goal that many scholars are tirelessly pursuing.In order to achieve early diagnosis of gallbladder cancer,the screening of molecular markers will be an important task for us in the future.Gene level studies will also provide an effective means for the treatment of gallbladder cancer,thereby significantly improving survival time and improving prognosis.ObjectiveTo investigate the expression of(hexokinase-2)HK2 in gallbladder carcinoma tissues and paracancerous tissues,analyze the relationship between its expression status and clinicopathological features and prognosis of gallbladder carcinoma,and study the proliferation and invasion of gallbladder cancer cells Changes in transfer capacity after HK2 silencing.MethodsDetect the expression of HK2 in 124 cases of gallbladder carcinoma and 40 cases of paracancerous tissues by immunohistochemistry(IHC).The effect of HK2 on the proliferation of GBC cell lines was examined by MTT assay and cell clone formation assay,and the potential role of HK2 in GBC cell metastasis and invasion was measured by Transwell assay.The proliferation,invasion and metastasis of GBC-SD cells and NOZ cell lines after HK2 silencing were detected.ResultsIn this study,we found that HK2 expression was significantly higher in GBC tissues than that in non-tumor samples,and the HK2 status was strikingly associated with late TNM stage and distant metastasis using immunohistochemistry(IHC)staining(P<0.05).Furthermore,its status was significantly correlated with shorter overall survival rate(P=0.0339)and multivariate analyses demonstrated that HK2 and the late TNM stage could act as an independent prognostic factor(P<0.05).HK2 plays an important role in the proliferation,invasion and metastasis of gallbladder cancer cells.Our in vitro experiment then unveiled that the proliferative capacity,invasion and migration abilities were markedly reduced in both GBC-SD and NOZ cell lines transfected with siRNA-HK2.Conclusions1.The results of this study indicate that HK2 is highly expressed in gallbladder carcinoma and the expression level is closely related to TNM stage and distant metastasis2.HK2 plays an important role in the proliferation,invasion and metastasis of gallbladder carcinoma.Interfering with the expression of HK2 can significantly reduce the proliferation,invasion and metastasis of gallbladder carcinoma cells.The targeted intervention of HK2 expression is expected to be an effective method for the treatment of gallbladder cancer.