Decreased Nuclear Expression Of FTO In Human Primary Hepatocellular Carcinoma Is Associated With Poor Prognosis

BackgroundPrimary liver cancer is one of the most common tumors in the world,and the main type is hepatocellular carcinoma,which has a high morbidity and mortality,which greatly harms human life and health.The main reasons for the poor prognosis of liver cancer patients are the rapid progress of metastasis of liver cancer in the early stage,the high recurrence and metastasis of tumors after surgical resection,and the effect of drug treatment varies widely among individuals.Therefore,the current research direction of liver cancer mainly lies in biological therapy and molecular targeted therapy,the main purpose is to be able to prevent and diagnose in the late stage of liver cirrhosis or early tumors,or to inhibit the metastasis of tumors after tumors have occurred.Therefore,there is an urgent need to find effective prediction and diagnostic targets to improve the prognosis of HCC.RNA methylation modification has been found to be related to the occurrence and development of various tumors in recent years.N6-methyladenosine(m6A)modification,as the most abundant internal modification in eukaryotic mRNA,has been shown to regulate hepatocellular carcinoma.Develop and influence prognosis.FTO,as the first mRNA demethylase of mRNA,can regulate the stability of mRNA by regulating the level of m6A and participate in the development and regulation of different types of tumors.However,the regulation and clinical significance of FTO expression in hepatocellular carcinoma is not clear.Therefore,we examined the expression pattern of FTO in hepatocellular carcinoma tissues and determined its relationship with clinicopathological factors and prognosis of patients with liver cancer.AimsTo detect the expression pattern and clinical significance of FTO in hepatocellular carcinoma,and to explore the effect of FTO on the malignant phenotype of liver cancer.Methods1,Collect frozen samples of tumor-corresponding tissues of patients with liver cancer,extract proteins and RNA to detect the expression difference of FTO in cancer and adjacent tissues.2,In paraffin pathological specimens containing cancer and corresponding adjacent tissues,the expression pattern and expression level of FTO were detected by immunohistochemical staining,and tissue specimens were divided into FTO low expression group and normal expression group based on the integrated optical density value.3,Collect follow-up data of patients and analyze the correlation between FTO and adverse prognostic features such as tumor size,liver cirrhosis,tumor differentiation,distant metastasis and vascular invasion.4,Construct FTO differentially expressed hepatocellular carcinoma cells,and determine the effect of FTO on liver cancer metastasis by transwell experiment.Results1,FTO protein and mRNA expression in cancer tissues of patients with liver cancer decreased.2,FTO is mainly located in the nucleus of cancer cells,and the down-regulation of FTO nuclear expression is related to tumor metastasis,vascular invasion,tumor size and other clinical indicators.3,Down-regulation of FTO nuclear expression is associated with a reduction in overall survival and tumor-free survival in patients with liver cancer.4,In vitro experiments showed that interference with FTO expression had no significant effect on the migration and invasion ability of liver cancer cells,but affects the expression level of m6A.Conclusion1,The expression of FTO is down-regulated in liver cancer tissues,especially the nuclear expression,and the decrease of FTO expression is related to poor prognosis.2,FTO does not affect the migration and invasion ability of liver cancer cells in vitro,but affects the expression level of m6A.