| Objective: This study aimed to investigate associations between HJURP gene polymorphism and clinical data in the treatment with apatinib plus tegafur-paced chemotherapy for advanced hepatocellular carcinoma(HCC).Methods: We collected clinical data and peripheral blood samples of 32 patients with advanced hepatocellular carcinoma who received treatment with apatinib plus tegafur-paced chemotherapy and used high-throughput sequencing platforms for gene sequencing to analyze the relationship between the SNP and efficacy,prognosis and adverse events.Results: 1.The objective response rate(ORR)of 32 patients was 6.25%,and the disease control rate(DCR)of 32 patients was 53.13%.According to statistics,the polymorphisms at seven loci of HJURP gene have no significant correlation with objective response rate(ORR)and disease control rate(DCR)(P>0.05).Baseline AFP level is correlated with DCR(P<0.05)and is an independent influencing factor of DCR.The disease control rate of AFP<400(ng/ml)is 0.17 times of AFP≥400(ng/ml)(95%CI: 0.03-0.99,P=0.049).2.The m PFS of 32 patients with advanced hepatocellular carcinoma was7.23 months.The m PFS of patients with rs10511 locus A/G+G/G genotype was longer than that of patients with A/A genotype by 1.22 months(8.45 months vs.7.23 months),but the difference was not statistically significant(P=0.704);The m PFS of patients with rs12582 locus and C/T+T/T genotype was longer than that of patients with C/C genotype by 1.22 months(8.45 months vs.7.23 months),but the difference was not statistically significant(P=0.704);rs3771333 locus A/C genotype m PFS was longer than A/A genotype m PFS by 4.50 months(10.7months vs 6.21 months),the difference was not statistically significant(P=0.135);The m PFS of patients with C/G+G/G genotype at rs3821238 was longer than that of patients with C/C genotype by 1.84 months(8.45 months vs 6.61 months),the difference was not statistically significant(P=0.914);The m PFS of patients with C/C genotype at rs3732215 locus was longer than that of patients with C/G+G/G genotype by 2.9 months(8.90 months vs 6.00 months),the difference was not statistically significant(P=0.198);The m PFS of patients with G/A+A/A genotype at rs3806589 was longer than that of patients with G/G genotype by 1.22 months(8.45 months vs.7.23 months),the difference was not statistically significant(P=0.843);The m PFS of patients with G/G genotype at rs2286430 locus was prolonged by 2.8 months(8.80 months vs 6.00 months)compared with G/A+A/A genotype m PFS,and the difference was not statistically significant(P=0.356).3.The m OS of 32 patients with advanced hepatocellular carcinoma was 8.90 months.The m OS of patients with A/G+G/G genotype at rs10511 locus was 0.66 months longer than that of patients with A/A genotype(9.24 months vs 8.58months),the difference was not statistically significant(P=0.577);The m OS of patients with C/T+T/T genotype at rs12582 was 0.66 months longer than that of patients with C/C genotype(9.24 months vs 8.58 months),the difference was not statistically significant(P=0.577);The m OS of patients with A/C genotype at rs3771333 locus was longer than that of patients with A/A genotype by 3.2 months(12.00 months vs.8.80 months),and the difference was not statistically significant(P=0.219);The m OS score of patients with C/G+G/G genotype at rs3821238 site was 0.92 months longer than that of patients with C/C genotype(9.20 months vs8.28 months),the difference was not statistically significant(P=0.805);The m OS of patients with C/C genotype at rs3732215 locus was 0.53 months longer than that of patients with C/G+G/G genotype(8.98 months vs 8.45 months),the difference was not statistically significant(P=0.846);The m OS of patients with G/G genotype at rs3806589 was 0.34 months longer than that of patients with G/A+A/A genotype(9.24 months vs 8.90 months),and the difference was not statistically significant(P=0.467);The m OS of patients with G/G genotype at rs2286430 locus was 0.32 months longer than that of patients with G/A+A/A genotype(8.90 months vs 8.58 months),and the difference was not statistically significant(P=0.664).4.Univariate analysis of PFS showed that the clinicopathological characteristics and polymorphism of seven loci of HJURP gene were not associated with PFS(P > 0.05).5.Univariate analysis of OS showed that liver tumor size was related to OS(P < 0.05).Multivariate analysis showed that liver tumor size was still associated with OS,and the risk of death in patients with liver tumor size > 5cm was 11.95 times higher than in patients with liver tumor size < 5cm(95%CI: 1.84-77.58,P=0.009).The polymorphism of seven loci of HJURP gene was not related to OS(P > 0.05).6.The results of the study on the genotypes of the seven loci of HJURP gene and the occurrence of thrombocytopenia showed that rs3821238,rs3732215,and rs2286430 were related to the occurrence of thrombocytopenia(P<0.05).However,after adjusting for confounding factors,the results showed that there was no significant difference between rs3821238,rs3732215,rs2286430 and thrombocytopenia(P>0.05).7.The results of the study on the genotypes of the seven loci of the HJURP gene and the occurrence of proteinuria showed that none of the loci were related to the occurrence of proteinuria(P>0.05).However,after adjusting for various potential influencing factors,the results showed that rs3732215 was associated with proteinuria,and the C/G+G/G genotype of rs3732215 was 0.158 times more likely to have proteinuria than the C/C genotype(95%CI: 0.026～0.960,P=0.045).Conclusions: HJURP gene polymorphism was not related to ORR,DCR,PFS,and OS in 32 patients with advanced hepatocellular carcinoma who received apatinib combined with tigio-beat chemotherapy.The rs3821238 locus,rs3732215 locus,and rs2286430 locus are associated with thrombocytopenia,and rs3732215 locus is associated with proteinuria. |
PDF Full Text Request