Application Of Whole Exome Sequencing In The Study Of Hepatocellular Carcinoma Metastasis

Objective Hepatocellular carcinoma(HCC)is the most common malignancy in our country,The latest figures show that more than half of new cases are in China each year.Which is characterized by early detection rate is low,the clinical treatment is poor.With the development of medical echnology,the emergence of genome-wide exome sequencing technology,the study of various aspects of the disease at the genetic level to provide more in-depth understanding of the opportunity.In this experiment,the whole genome sequencing technology(Whole exome sequence)will be different metastatic potential of liver cancer tissue and its adjacent tissue,the transfer potential of different performance of six kinds of liver cancer cell lines were sequenced,To explore changes in genes associated with hepatocellular carcinoma metastasis.Methods 12 cases of HCC patients were divided into high metastatic potential group and low metastasis potential group according to the corresponding examination results.Each group have six patients.The DNA of tumor tissue and adjacent tissues were extracted and subjected to whole exome sequencing.Six groups of hepatocellular carcinoma cell lines with different metastatic potentials were cultured for exome sequencing.The results were compared with bioinformatics to screen out the genes related to the metastasis and development of hepatocellular carcinoma.Results 1.In the comparison of high and low metastatic potentials,we found that 40 influential gene mutations occurred in 3 or more patients with high potential metastatic hepatocellular carcinoma,including UIMC1(rs3733876C/T)、SEMA3C(rs1527482G/A)、SAMD9(rs10279499G/T)、RECK(rs16932912G/A)、PDLIM4(rs4877G/T)、LIMK2(rs3747154A/G)、CRIM1(rs3821169G/T)Of the mutation and hepatocellular carcinoma metastasis are closely related.2.There are 13 genes that are more than or equal to 2 samples and only mutations appear in tumor tissue.Among them,ADGB、CTNNB1(rs12191341A/G,rs121913228T/G)、PTPN11(rs121918457 C/T,rs397507546 G/T)、TP53 and TRPS1 are related to the formation of hepatocellular carcinoma.3.There were only 10 SNP loci in HCC-LM3,MHCC-97 L and MHCC-97 H,and only 2 mutations were found in hepatocellular carcinoma cells with lowmetastatic potential.Which is reported to be related to tumor metastasis CAPZB(rs79308175C/T)、CSF1R(rs10079250A/G)、HSPA5(rs143920039A/T)、SORBS3(rs2449331T/C,rs3758036C/T)、RASAL3(rs146624357G/A,rs142945276 C/T).4.Among the three high metastatic potential hepatocellular carcinoma,69 SNP-altering genes were only present in HCC-LM3 、and 30 SNPs were only present in MHCC-97 L and MHCC-97 H.Mutations of EHBP1(rs77403174T/C)、FAM189B(rs150296362C/T)、 SERPINB13(rs144903442G/A)、 ARHGEF1(rs2303797C/T)were reported to be associated with tumor metastasis and recurrence.Conclusion 1.Mutations in UIMC1、SEMA3C、SAMD9、RECK、PDLIM4、LIMK2、CRIM1、CAPZB、CSF1R、HSPA5、SORBS3、RASAL3、EHBP1、FAM189B、SERPINB13、ARHGEF1 are related to the metastasis of hepatocellular carcinoma.2.CAPS2,CENPJ,EDAR,PCDHB10 and other gene mutations and hepatocellular carcinoma metastasis value of concern.3.Mutations of ADGB、CTNNB1、 PTPN11、TP53、TRPS15 are associated with the formation of hepatocellular carcinoma.