Correlation Between Tumor Mutation Load And Clinical Characteristics And Prognosis Of Patients With Hepatocellular Carcinoma

Objective:Hepatocellular carcinoma(HCC)has a high incidence and poor prognosis.Its occurrence and development is a multi-step process,including the accumulation of genetic variations and the activation of different signal transduction pathways to drive normal cells to gradually transform into malignant cells.In recent years,with the deepening of genomics research,the understanding of the genetic basis related to the occurrence and development of HCC has been deepened,but the exact molecular mechanism of the occurrence and development of HCC remains unclear.This paper aims to analyze the sequencing results of 138 HCC patients who underwent radical resection by using NGS technology to detect gene mutation in HCC tissues,summarize their gene mutation characteristics,and explore the relationship between tumor mutation burden and tumor recurrence in HCC patients who underwent radical resection combined with clinical information such as recurrence and survival..Methods:HCC tissue specimens were collected from 138 patients who underwent radical resection of hepatocellular carcinoma and underwent genetic testing in the Affiliated Hospital of Qingdao University from January 2017 to March 2019.The diagnosis of HCC in all specimens was confirmed by pathology.Genomic DNA was extracted from tissue samples and blood samples using QIAamp DNA FFPE tissue kit and QIAamp DNA blood sample Midi kit.Sequencing analysis of genomic DNA was performed in the laboratory of Origi Med(Shanghai,China),CAP certification laboratory,and high-throughput sequencing platform was used to obtain genomic mutations using Illumina Nova Seq 6000.The TMB score was calculated by counting the number of cell mutations per megabase(Mb)of the sequence examined.At the same time,the basic information,serological test results,tumor pathological characteristics and follow-up data of patients were recorded.Qualitative data were tested by ?2 test,quantitative data were tested by t test,and factors with P < 0.05 were included in logistic regression analysis.Kaplan-Meier method was used to analyze the effect of TMB on recurrence of patients,and P<0.05 was considered statistically significant.Result:There were 123 males and 15 females in this group,with an average age of 57.0 years(31.0-78.0 years).The median follow-up time was 16.1 months(6.0-30.0 months)until 30 September 2019 or when the patient died.A total of 263 mutated genes were detected in this group,totaling 827 mutations,with an average of 6.0 mutations/case.TMB results were obtained in all specimens,with a median TMB of 5.4 Muts/Mb(0-28.4 Muts/Mb)and a TMB 75% quantile of 8.5 Muts/Mb.Genes with higher mutation frequency were TP53,TERT,CTNNB1,etc.,and the main mutation form was single nucleotide site mutation;signal pathways with higher mutation frequency were P53 pathway,Wnt pathway,chromatin remodeling related pathway,etc.Univariate analysis showed that the proportion of patients with high tumor mutation burden(TMB-H)was significantly higher in patients older than 60 years,hypertension,diabetes,CTNNB1 mutation and LRP1 B mutation(P < 0.05).Incorporating the above factors into multivariate analysis showed that LRP1 B mutation was an independent risk factor for TMB-H(P=0.009,OR=4.828,95% CI:1.493-15.583).The median time to disease progression was 14.6 months and 18.0 months in the TMB-H and TMB-L groups(2 = 3.909,P = 0.048),and the 1-year recurrence rates in these two groups were 33.3% and 15.9%,respectively(P = 0.024)..Conclusion:I In this group,TP53,TERT and CTNNB1 were the main mutations,and the main mutation forms were single nucleotide site mutations.The main pathways were P53 pathway,Wnt pathway,chromatin remodeling related pathways.Hypertension,diabetes,CTNNB1 mutation and LRP1 B mutation had an impact on the occurrence of high TMB.LRP1 B mutation was an independent risk factor for high TMB.TMB-H is associated with short-term recurrence after radical resection in HCC patients.These findings help us to further understand the molecular mechanism of the occurrence and development of HCC and provide a theoretical basis for the precise treatment of HCC.