The Expression And Clinical Significance Of Rab1A And RAB31 In Hepatocellular Carcinoma

Hepatocellular Carcinoma as the most common pathological type of Primary Liver Cancer,it is also the third cause of cancer-related death in the world.Surgery as the main selection of HCC treatment nowadays,some patients have obtained satisfactory curative effect from heaptectomy,however,the 70% of 5-year recurrence rate and the 5-year overall survival rate is of less than 50% remain difficult to overcome.Because of the silent and rapid progresses,many patients have lost the chance of surgery when they are diagnosed of HCC.Nowadays,some treatments have achieved some progression in advanced liver cancer such as Transcatheter arterial chemoembolization,molecular targeted therapy,biotherapy,immunity therapy,ect.However,due to the high malignant degree of HCC cells and tend to metastasis and spread easily.HCC still poses a heavy burden on the life and health of Chinese people.The growth,development,maturation and secretion of eukaryotic cells are accompanied by the transport and conduction of proteins in the body.Precise activity and regulation between human organelles play an important role in the operation of life activities and are also the hot spots of research all along.The organelles transport the vesicles to the designated sites through the process of entrapment and vomiting,while various proteins involved in the formation,transport,adhesion and precise delivery of vesicles,the Rab GTPases is one of the proteins.It has been confirmed that mutations in Rab proteins and loss of regions will result in protein mismatches,which are involved in the development of many diseases,including tumors.Rab1 A is a member of the Rab family of proteins that anchors the Golgi apparatus to the endoplasmic reticulum membranes.Controlling vesicle transport between them,the disorder of the Rab1 A will result in the accumulation of proteins in the endoplasmic reticulum.Inducing the Endoplasmic Reticulum Stress signal path,which is the unfolded protein response.The UPR coordinates protein synthesis and degradation,molecular chaperones expression and cell cycle progression and apoptosis.Abnormal expression of Rab1 A has been confirmed to be involved in a number of diseases,such as Parkinson's disease,Aspirin exacerbated respiratory disease,etc.At the same time,Rab1 A also involves the regulation of mTORC1 pathway involved in the development of colon cancer,prostate cancer and other malignancies.Rab31,another member of the Rab family of proteins,is derived from human melanocytes firstly(and subsequently cloned from human platelets),consisting of 194 amino acids,Rab31 plays a role in the regulation of early endosome-transport of late endosomes.Especially be involved in epidermal growth factor receptor.It has been experimentally confirmed that high expression of Rab31 promotes the proliferation of breast cancer cells and is also involved in the progress of ovarian cancer and glioblastoma.In most tumors Rab31 shows its malignant invasion ability,but its mechanism of affecting tumor cell apoptosis and proliferation is still under discussion.Above all,the Rab1 A and Rab31 are all regulatory proteins of vesicle transport and participate in the transport of Golgi and endoplasmic reticulum.Research in tumors is still in its infancy.And Some studies have confirmed that both are also involved in cell autophagy and senescence,and autophagy of cells is also an important mechanism for tumor development.Therefore,further confirmation and affirmation of the biological effects of both will be of great significance,in this experiment we are proving its significance in tumor development by detecting the expression of two indicators in HCC.ObjectiveTo detect the expression of Rab1 A and Rab31 in HCC and to investigate the relationship between them and clinical indicators of patients with HCC as well as the patients? postoperative outcome.MethodsThe number of 62 specimens after radical liver cancer resection(The postoperative pathological results were confirmed as HCC)and its corresponding tissue specimens adjacent to carcinoma,normal liver tissue specimens were collected from the First Affiliated Hospital of Zhengzhou University from 2011 to 2012.The expression of Rab1 A and Rab31 in these specimens was detected by streptavidinperosidase(SP)immunohistochemistry.Comparing the expression differences between cancer tissues,paracancer tissues and normal liver tissues.The relationship between them and the clinical pathological characters of 62 HCC patients was analyzed.The long-term follow-up of all patients was performed.Every patients? postoperative overall survival times was recorded.Multivariate and univariate analysis were performed on the survival data of patients.Survival analysis was used to confirm the relationship between this two indexes and postoperative prognosis of patients with HCC.Results1?The comparison of the protein expression in primary lesions,paracancer tissues and normal liver tissues by Immunohistochemistry found that the positive expression of Rab1 A and Rab31 in HCC tissues(93.55%,96.77%)were higher than those in paracancer tissues(48.39%,67.74%),and in the normal tissues(15%,5%),the differences was statistically significant(P <0.001).2?Analysis of the relationship between the Rab1A/Rab31 and the clinical characters of 62 patients found that the expression level of Rab1 A was significantly associated with tumor?s TNM staging,portal vein tumor thrombus,liver cirrhosis,vascular invasion,tumor differentiation,tumor size,plasma alpha fetoprotein(AFP)levels(P<0.005).While there was a significant correlation between the expression of Rab31 and patients? Child staging,BCLC staging,TNM staging,liver cirrhosis,invasion of vascular Invasion,and the numbers of tumors(P <0.005).Statistical analysis showed no significant correlation between the two indicators(P = 0.149).3?The univariate analysis 62 patients? data found that tumor stage,cirrhosis,vascular invasion,pathological differentiation and other factors affect the postoperative overall survival(P <0.005).The relative high expression of Rab1 A and Rab31 was also risk factors for overall survival after HCC resection(P = 0.026,P <0.001).Survival curves showed that the overall survival rates of HCC patients with high Rab1 A and Rab31 expression were lower than those with corresponding low expression(P <0.005).Conclusion1?Rab1A and Rab31 were all concentrated expressed in HCC tissues and were less in paracancer and normal liver tissues.High expression of Rab1 A is associated with tumor TNM staging,portal cancer thrombosis,and cirrhosis,ect;High expression of Rab31 is associated with factors such as Child's grade,BCLC stage,and multiple tumors,ect.2?Patients with high expression of Rab1 A and Rab31 showed poor prognosis after operation,and the overall survival time was significantly shortened,targeting researches on both may provide new directions for the treatment of HCC.