Clinical study on the influence of plasma cell marker genes on sorafenib sensitivity in hepatocellular carcinoma
Objective To construct a prognostic risk model of hepatocellular carcinoma(HCC)based on signature genes of plasma cells and investigate the influence of risk score and signature genes of plasma cells on the prognosis of HCC patients and their sensitivity to sorafenib treatment.Methods The landscape of HCC was revealed through single-cell RNA sequencing,using Seurat,DoubletFinder and Har-mony R packages.Plasma cells infiltration in the liver cancer institute(LCI)and the cancer genome atlas-liver hepatocellular carcinoma(TCGA-LIHC)cohorts was assessed using the CIBERSORT deconvolution algorithm.Signature genes of plasma cells was identified through single-cell RNA sequencing,and subse-quently a prognostic risk model was constructed through univariate Cox-least absolute shrinkage and selec-tion operator(LASSO)-multivariate Cox analysis.The Oncopredict algorithm was utilized to evaluate the effect of prognostic risk score and signature genes of plasma cells on sorafenib sensitivity.Wilcoxon test was employed to compare significance between different groups,Kaplan-Meier and Log-rank tests were em-ployed for survival analysis and Pearson correlation coefficient was used to measure the correlation between two variables.Results High plasma cells infiltration was associated with adverse prognosis in both LCI co-hort[hazard ratio(HR)=1.684,95％confidence interval(CI):1.09-2.61,P＜0.05]and TCGA-LIHC cohort[HR=1.64,95％CI:1.58-3.25,P＜0.05].Compared to low-risk patients,those in the high-risk group exhibited poorer overall survival(OS)[HR=2.27,95％CI:1.58-3.25,P＜0.01].However,patients in the high-risk group exhibited lower 50％inhibitory concentration(IC50)of sorafenib[12.87(3.11,43.27)vs.15.135(7.58,32.97),U=10 324,P＜0.01],indicating increased sensitivity to sor-afenib treatment.The expression of plasma cells signature genes was negatively correlated with sorafenib IC50[SEC61A1(R=-0.30,P＜0.01);DNAJC1(R=-0.22,P＜0.01);EIF5B(R=-0.17,P＜0.01);DNAJB4(R=-0.22,P＜0.01);ST6GALNAC4(R=-0.29,P＜0.01);CCDC88A(R=-0.42,P＜0.01)],and the correlation of SEC61 A1,ST6GALNAC4 and CCDC88A with sorafenib IC50 was stronger than that of commonly used sorafenib response prediction markers MAPK1,MAPK3 and KDR with sorafenib IC50(-0.30,-0.29,-0.42 vs.-0.27,-0.21,-0.20).Conclusion The expression of signature genes of plasma cells is positively correlated with sorafenib sensitivity in HCC,suggesting their potential as biomar-kers predicting sorafenib response in clinic.
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