Clinical Characteristics And Molecular Mechanism Of Primary Liver Cancer In Yanbian Area

Objective:China is on the whole to have a high endemicity area of primary liver cancer,being the fourth most prevalent tumor type and the third leading cause of cancer-related deaths.The data from the China Cancer Annual Report 2012 showed that the Yanji is considered one of the high endemicity areas of primary liver cancer.However,there have been no a statistically significant reports on the viral infection and pathogenesis of primary liver cancer in the area.Therefore,in this study,we retrospectively analyzed the clinical data of patients with primary liver cancer to understand clinical characteristics and high-throughput transcriptome sequencing for the tissues of liver cancer and adjacent no-tumor tissues to analyzed pathogenesis from the molecular level,which may provide scientific basis for the prevention and treatment of primary liver cancer in Yanbian area.Methods:Retrospectively investigating and analyzing the clinical data of the 3537 cases history,which is been diagnosed caused by primary liver cancer from January 2000 to July 2016 in the Affiliated Hospital of Yanbian University.After informed consent,liver cancer tissues and adjacent no-tumor tissues were collected from primary liver cancer patients for high-throughput transcriptome sequencing.Results:A total of 3537 cases of primary liver cancer patients,including 2581 cases were males and 956 cases were females,the percentage of male and female is 2.7:1.The PLC patients with liver cirrhosis were 2865 cases and without liver cirrhosis were 672 cases.The overall number of patients of primary liver cancer was rising from 2000 to 2015.The majority of primary liver cancer patients were infected with HBV from 2000 to 2009.However,HCV infection was the dominant after 2010.HBV-related PLC patients had the age of onset less than HCV-related PLC patients(P<0.05).The proportion of males in HBV-related PLC patients was the highest(P<0.05).The proportion of liver cirrhosis were higher than without cirrhosis in the HBV-related PLC patients,HCV-related PLC patients,HBV with HCV related PLC patients,and non-viral infection PLC patients,especially,the proportion of was highest in HBV combined with HCV related PLC patients(P<0.05).The proportion of HBV infection PLC patients was highest in Han,whereas the proportion of HCV infection PLC patients was highest in Korean(P<0.05).The proportion of males in each age group was higher than females.The onset age of male patients was mostly 40-60 years,while the onset age of females was more than 60 years(P<0.05).The less than 40 years and 40-60years age groups was mainly HBV infection,while the 60 years or older age group was mainly HCV infection(P<0.05).The onset age of male PLC patients was 58.95±10.94 years,and the onset age of female PLC patients was 63.01± 10.12 years.The onset age of male is lower than females(P<0.05).The male PLC patients had more cirrhosis than women(P<0.05).The onset age of PLC patients with cirrhosis was significantly lower than without cirrhosis(P<0.05).A total of 4927 differentially expressed genes in liver cancer tissue and adjacent no-tumor tissues were identified by transcriptome sequencing,and the number of genes in tumor tissues including 159 up-regulated and 4768 down-regulated ones.Genes with increased expression in tumor tissues were analyzed by GO,we found that genes such as BBOX1,HMGCS2,ADH4,VCAN,COL1A1,and POSTN may be involved in the progression of liver fibrosis to liver cancer.The KEGG pathway revealed that the P13K-Akt signaling pathway,focal adhesions,extracellular matrix receptor interactions,chemokine signaling pathways,interactions between cytokines and cytokine receptors,cancer pathways,NF-?B signaling pathways may be involved in the progression of liver fibrosis to liver cancer.Conclusion:The overall number of patients of primary liver cancer was rising from 2000 to 2015.The majority of primary liver cancer patients were infected with HBV from 2000 to 2009.However,HCV infection was the dominant after 2010.The incidence rate of males was significantly higher than females;the average age of females was five years older than males.The age of PLC of HBV infection patients was younger,and mainly in Han.However,the age of PLC of HCV infection patients was higher,mainly in Korean.The pathological basis of PLC patients were mainly cirrhosis.A total of 4927 differentially expressed genes.Genes with increased expression in tumor tissues were analyzed by GO,we found that genes such as BBOX1,HMGCS2,ADH4,VCAN,COL1A1,and POSTN may be involved in the progression of liver fibrosis to liver cancer.The KEGG pathway revealed that the P13K-Akt signaling pathway,focal adhesions,extracellular matrix receptor interactions,chemokine signaling pathways,interactions between cytokines and cytokine receptors,cancer pathways,NF-?B signaling pathways may be involved in the progression of liver fibrosis to liver cancer.