循环淋巴细胞亚群整合指数的建立及其在接受TACE治疗的不可切除肝癌患者中的预后价值OA

Background and purpose:Transarterial chemoembolization(TACE)is the primary treatment modality for unresectable hepatocellular carcinoma(HCC);however,patient outcomes vary considerably.This study aimed to develop a multiparametric integrated model incorporating lymphocyte subsets[the circulating lymphocyte subsets integrated index(CLSII)]and to evaluate its prognostic value in patients with unresectable HCC undergoing TACE.Methods:A retrospective analysis was conducted on HCC patients who received initial TACE or TACE combined with ablation therapy at Zhongshan Hospital,Fudan University,between January 2015 and December 2018.Baseline characteristics,including demographics,clinicopathology,imaging assessments,biochemistry,coagulation function,and lymphocyte subsets,were collected via the hospital information system.The clinical value of lymphocyte subsets was explored using the Mann-Whitney U test,Kaplan-Meier method,log-rank test,and Cox proportional hazards models.The Least Absolute Shrinkage and Selection Operator(LASSO)regression was employed to screen peripheral inflammation-related indicators and construct the CLSII.The CLSII was calculated as the sum of the standardized values of selected indicators weighted by their respective coefficients.The predictive performance was compared with that of conventional inflammatory scores,including the systemic immune-inflammation index(SII),platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio(NLR),modified Glasgow prognostic score(mGPS),lymphocyte-to-monocyte ratio(LMR),Glasgow prognostic score(GPS),and prognostic nutritional index(PNI),by using the concordance index(C-index)and time-dependent receiver operating characteristic(ROC)curves.Finally,a prognostic nomogram incorporating CLSII,Eastern Cooperative Oncology Group(ECOG)performance status and tumor diameter was established based on multivariate Cox regression results.The accuracy and clinical net benefit of the model were evaluated using calibration curves and decision curve analysis(DCA).Results:A total of 966 patients were ultimately included in this study.Survival analysis indicated that patients with high B cell counts(>169/μL)and high Th cell counts(>503/μL)exhibited significantly superior survival rates(P<0.05).Multivariate Cox analysis confirmed B cell count as an independent protective prognostic factor[hazard ratio(HR)=0.81,95%CI:0.64-0.93,P=0.031].LASSO regression analysis identified seven variables for constructing the CLSII:platelet(PLT),neutrophils,C-reactive protein(CRP),albumin(Alb),natural killer(NK)cells,B cells and T helper(Th)cells.Their corresponding regression coefficients were 0.212,0.155,0.111,-0.124,-0.124,-0.140 and-0.067.Patients in the high-CLSII group demonstrated significantly inferior survival compared to the low-CLSII group.Multivariate analysis incorporating clinical covariates identified CLSII as an independent prognostic risk factor(HR=2.56,95%CI:2.01-3.27,P<0.001).In terms of predictive performance,CLSII outperformed NLR,PLR,and SII,achieving higher C-index and time-dependent area under the curve(AUC)values for 1-,2-and 3-year survival(0.735,0.693 and 0.666,respectively).Furthermore,the constructed prognostic nomogram integrating CLSII,ECOG performance status and tumor diameter showed high consistency between predicted probabilities and actual survival on calibration curves.DCA confirmed that the nomogram model provided superior clinical net benefit across a wide range of threshold probabilities compared to the clinical model alone or the single CLSII index.Conclusion:CLSII serves as a prognostic biomarker integrating information on both immune defense and pro-tumor inflammation,demonstrating superior predictive accuracy compared to traditional inflammatory indices.The CLSII-based prognostic nomogram exhibits excellent calibration and clinical net benefit,offering a tool for individualized survival prediction in patients with unresectable HCC undergoing TACE.