Expression Of MACC1 And Its Relationship Between The Clinicopathological Features And Prognosis Of Klatskin Tumor

Background:Hilar bile duct carcinoma,also known as Klatskin,is a kind of bile duct carcinoma,which is located in the hepatic duct cystic,bifurcation of the hepatic duct,left hepatic duct and right hepatic duct.As one of the most common subtypes of cholangiocarcinoma,it accounts for 50%-60%.Its etiology is complex,some studies suggest that liver cirrhosis,hepatitis B,hepatitis C is the risk factor,but the mechanism is not yet clear.The bile duct cancer incidence rate of patients with primary sclerosing cholangitis is as high as 15%,as is considered to be precancerous lesions of bile duct cancer.Klatskin tumor is close to the portal vein and hepatic artery,so it is easy to infiltrate the peripheral blood vessels.Meanwhile,Klatskin tumor can be transferred to the liver along the bile duct wall.At present,radical surgery is the first choice for the treatment of Klatskin tumor.But not all patients benefit from surgery.For the late stage patients,the best operation time was lost,there is no choice but palliative treatment.Metastasis associated gene 1(MACC1)is a newly discovered gene associated with tumor metastasis.It is an important bridge of HGF/C-Met signaling pathway.MACC1 can induce cell proliferation,differentiation and migration by regulating signal transduction pathway,which is closely related to tumor metastasis.In recent years,domestic and foreign scholars have found that the high expression of MACC1 is associated with high metastasis rate and poor prognosis of colorectal cancer,gastric cancer,ovarian cancer,hepatocellular carcinoma and other solid tumors.At present,there is a few of research correlation between MACC1 and clinicopathological features and prognosis of Klatskin.In this study,the expression of MACC1 in Klatskin tumor was detected by immunohistochemistry and fluorescence quantitative PCR,and the relationship between expression of Klatskin and pathological features and prognosis was analyzed.Methods:Collect pathological sections of postoperative patients with Klatskin.All specimens were embedded by paraffin,being detected the expression of MACC1 protein of tumor tissue and adjacent normal tissues by immunohistochemical.The other intraoperative sampling,Klatskin tumor surgical removal of tissue and non tumor tissue(bile duct tissues of bile duct cyst who underwent surgical treatment)were processed in the-80? liquid nitrogen environment,real time fluorescence quantitative PCR detected the expression of MACC1mRNA in Klatskin tumor tissues and adjacent tissues and normal bile duct tissues.The relationship between the expression of MACC1 and clinicopathological features and prognosis was analyzed.Statistical software SPSS22.0(statistical package for Social Sciences)was used to analyze the MACC1 expression in Klatskin tumor and normal tissues,and analyze the relationship between MACC1 expression and clinical pathological parameters such as the sex,age,tumor size,differentiation degree,lymph node metastasis,tumor recurrence,and the relationship between MACC1 expression and prognosis of patients with Klatskin tumor.Results:1.Immunohistochemistry showed that the positive rate of MACC1 protein expression was 54.3%(25/46)in the Klatskin tumor tissues,which was higher than that in the adjacent tissues 10.9%(5/46,p<0.05).Real time fluorescent quantitative PCR results showed that the expression level of MACC1mRNA in Klatskin tumor tissue was about 10 times than normal bile duct tissues,and 5 times than that in the adjacent tissue,the expression of MACC1mRNA in cancer tissue was 2 times higher than the normal group,the differences were statistically significant(p<0.05).2.The expression of MACC1 in tumor tissues of Klatskin was closely related to tumor size,recurrence and lymph node metastasis(P<0.05),but not with sex,age and degree of differentiation(P>0.05).3.Survival analysis indicated that the mean survival time of MACC1 positive patients with Klatskin tumors was 26.92 + 20.12 months and MACC1 negative patients with Klatskin tumors was 36.14 + 25.89 months.The survival time of patients with Klatskin tumors was significantly less than that of MACC1 negative patients with Klatskin tumors(p<0.05).Conclusions:1.MACC1 expression was significantly higher in Klatskin tumor.2.Expression of MACC1 was related to the tumor size,recurrence and lymphatic metastasis of Klatskin3.Expression of MACC1 would affect the prognosis of patients.