Study on Molecular Mechanism of Liver Metastasis in Patients with Late Colorectal Cancer by NGS Technique

[Objectives]To analyze the difference of gene expression between primary lesion and metastatic lesion in patients with advanced colorectal cancer with liver metastasis by NGS detection,and to further explore the molecular mechanism of liver metastasis in patients with advanced colorectal cancer.[Methods]In a case-control study combined with cohort study,NGS sequencing was performed in 9 patients with postoperative first-line cetuximab combined with chemotherapy,and retrospective analysis was made to find the biomarker that can predict the curative effect;then 9 samples of biomarker were prospectively verified;at the same time,9 cases of primary lesions(2 sites)and 9 cases of liver metastases were detected by WES.[Results]The mutation type of primary lesion was mainly Missense(missense mutation):a total of 1802 mutations were detected in the primary lesion samples of 9 patients,of which Missense accounted for 88.01%;a total of 2150 mutations were detected in the metastatic samples of 9 patients,of which Missense accounted for 87.67%.The results of Venn diagram showed that there were 1010 common mutations in primary and metastatic lesions,accounting for 42.4%.There were 819 genes in metastatic lesions,accounting for 34.4%;there were 553 unique genes in the primary lesion,accounting for 23.2%.The results of thermography showed that there were 7 mutant genes with more than 33.3%primary lesions,including APC,TTN,HDAC2,RELN,RHPN2,RYR3 and TP53;there were 13 mutant genes with metastatic lesions of more than 33.3%,including APC,RHPN2,TTN,TP53,COBLL1,DNAH12,DNAH17,EVC2,RYR3,SVEP1,SYNE1,ZNF197 and ZNF423,and the mutation rate of APC increased from 66.7%to 77.8%;TTN increased from 44.4%to 66.7%;RHPN2 rose from 33.3%to 66.7%;TP53 rose from 33.3%to 55.6%.COBLL1,DNAH17 and EVC2 rose from 22.2%to 33.3%.SVEP1,SYNE1,ZNF197 and ZNF423 were only expressed in metastatic lesions,and the expression increased from 0%to 33.3%.The results of GO enrichment showed that the top five mutant genes in colon cancer were KRAS,BRAF,TP53,APC and PI3 KCA.[Conclusions]The primary and metastatic lesions were mainly Missense;APC,TP53 mutation was a common mutant gene with high expression;the expression of PHPN2 and TTN mutant genes increased by 33.3%and 11.1%,respectively;the mutation rate of BRAF gene was the second in GO enrichment.