| Objective: To study the distribution characteristics of peripheral blood lymphocyte subsets(PBLS)in benign and malignant bone tumors,as well as its prognostic value for osteosarcoma.Methods: The clinical data of patients with benign and malignant bone tumors admitted to our hospital from January 2012 to June 2019 were collected,including general clinical data,peripheral blood lymphocyte subsets parameters and blood routine parameters.According to the inclusive and exclusive criteria,70 patients with malignant bone tumors(osteosarcoma group)and 70 patients with benign bone tumors(control group)were enrolled in this study.The differences of PBLS absolute counts,PBLS relative ratios and blood routine parameters between the two groups were compared with Mann-Whitney U test.In the cohort of osteosarcoma,the entire cohort was divided into several subgroups based on the variables of Enneking stage,recurrence or metastasis status and so on,the distribution characteristics and differences of PBLS absolute counts and PBLS relative ratios among different subgroups were compared with Mann-Whitney U test or Kruskal-Wallis H test;the predictive value of PBLS absolute counts,PBLS relative ratios and blood routine parameters for the prognosis of osteosarcoma was analyzed by the AUC of receiver operating characteristic(ROC)curve;the Kaplan-Meier curves were utilized to plot the survival curves of different subgroups,and the differences of survival in different subgroups were analyzed by the Log-rank test;the prognostic factors of survival for osteosarcoma were identified by the Cox regression analysis.Results:(1)A total of 140 patients were included in this study,including 70 osteosarcoma patients and 70 benign bone tumor patients.The median overall survival of osteosarcoma cohort was 34.90(4.60-76.90)months,and the 1-,3-and 5-year survival rates were 87.14%,54.28% and 22.86%,respectively.The patients in the control group were all benign bone tumor patients,including 8 cases(11.43%)of osteoid osteoma,50cases(71.43%)of osteochondroma and 12 cases(17.14%)of chondroma.(2)There existed no significant differences in PBLS absolute counts between osteosarcoma group and control group.While in the relative ratios of PBLS,patients in osteosarcoma group showed lower levels of CD4+/CD8+,CD19+/CD8+,CD16+CD56+/CD8+ and CD4+/CD3+(P<0.05).Concerning the blood routine parameters,the osteosarcoma group harvested higher levels of WBC,Neutrophil,Monocyte,PLT,NLR and PLR(P<0.05),while got a lower level of LMR(P<0.05).(3)Compared with patients in the subgroup of Enneking II or patients with no recurrence or metastasis,patients in the subgroup of Enneking III,with lung metastases at initial diagnosis or with recurrence or metastasis during treatment showed lower levels of CD3+CD4+ absolute count,CD19+absolute count,CD16+CD56+ absolute count,CD4+/CD3+ ratio,CD4+/CD8+ ratio,CD19+/CD3+ ratio and CD16+CD56+/CD3+ ratio(P<0.05),and got higher levels of CD3+CD8+ absolute count and CD8+/CD3+ ratio(P<0.05).(4)Regarding the prognostic values of PBLS parameters and blood routine test parameters for the overall survival of osteosarcoma,in PBLS parameters,the area under the receiver operating characteristic curve(AUC)of CD16+CD56+ absolute count,CD4+/CD8+ ratio,CD19+/CD3+ ratio and CD4+/CD3+ ratio were 0.638,0.781,0.657 and 0.768,respectively.In blood routine test parameters,the AUC of NLR,PLR,LMR and PNI were 0.720,0.632,0.639 and 0.718,respectively.(5)In univariate Cox regression analysis,preoperative neoadjuvant chemotherapy,surgery,chemotherapy,Enneking stage,ALP,CD19+ absolute count,CD16+CD56+ absolute count,CD4+/CD8+ ratio,CD4+/CD3+ ratio,CD19+/CD3+ ratio,NLR,PLR,PNI,LMR,WBC and Neutrophil were identified as prognostic factors for overall survival of osteosarcoma.In multivariate Cox regression analysis,preoperative neoadjuvant chemotherapy,surgery,chemotherapy,Enneking stage,ALP,CD4+/CD8+ ratio,CD19+/ CD3+ ratio,NLR,PLR and PNI were confirmed as independent prognostic factors for the overall survival of osteosarcoma.(6)In the subgroup of Enneking II/III stage,with initial lung metastasis and with no recurrence or metastasis after treatment,patients with CD4+/CD8+ ratio ≥ 1.30 or CD19+/CD3+ ratio≥0.11 got a relatively longer overall survival(P<0.05).Conclusion: Significant differences of PBLS distribution were observed between osteosarcoma patients and benign bone tumor patients,as well as in different subgroups of osteosarcoma patients.PBLS parameters can serve as prognostic predictors for the overall survival of osteosarcoma patients.The differences of PBLS parameters between osteosarcoma patients and benign bone tumor patients were mainly reflected in the relative ratios of PBLS.Significant differences were observed in PBLS absolute counts and PBLS relative ratios among the subgroups with different Enneking stages and with different recurrence or metastasis statuses.Among the parameters of PBLS,the ratio of CD4+/CD8+ and the ratio of CD19+/CD3+ can be used as prognostic predictors for the overall survival of osteosarcoma. |
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