| Background and PurposeBreast cancer is mostly estrogen-dependent.Compared with other types of breast cancer,the risk of recurrence of luminal breast cancer is low.But there are still a small number of patients with recurrence and metastasis.Several reports have suggested that the number of peripheral blood leukocyte can be ralated to host immunity response.Some peripheral blood-based parameters can be regarded as the independent prognostic factors in patients with colorectal cancer,lung cancer,gastric cancer or liver cancer.However,due to the lacking of relevant clinical study,it is not clear whether the peripheral blood-based parameters are related to prognosis of luminal breast cancer patients.The purpose of the present study was to identify the prognostic significance of various peripheral blood-based biomarkers and to determine the optimal cut-off value suitable for luminal breast cancer patients.Try to determine some the relevant mechanisms of peripheral blood-based parameters in luminal breast cancer.MethodsTwo hundred and fifty-nine cases were analyzed retrospectively.Receiver operating characteristics(ROC)curves,were performed to evaluate the prediction status of absolute lymphocyte count(ALC),absolute monocyte count(AMC),lymphocyte-to-monocyte ratio(LMR),neutrophil-to-lymphocyte ratio(NLR),and platelet-lymphocyte ratio(PLR).The LMR cutoff value for survival analysis determined by ROC analysis had tested by theχ2 maybe have a relationship with clinical pathological characteristics,performed Kaplan-Meier method,comparison between groups was using log-rank test.Multivariate analysis was carried out using Cox proportional hazard model.CD8~+T cells in peripheral blood were determined in 259 patients by flow cytometry,and analyzed.MCF-7 cells were co-cultured with CD8~+T,the apoptosis rate of tumor cells was detected by flow cytometry.Fas L antibody was added to the culture system to observe the changes of the apoptosis rate of tumor cells.The expression of Fas in MCF-7 and T47D breast cancer cells treated with 5-fluorouracil(5-FU)/paclitaxel was detected by fluorescence quantitative PCR.After MCF-7 cells treated with 5-FU were co-cultured with CD8~+T,the killing effect of CD8~+T on tumor cells was detected by WST-1 method.Western blot was used to detect the expression of Fas in MCF-7 breast cancer cells and the expression of Fas L in CD8~+T cells.Fas L antibody was added to the culture system to observe the changes of CD8~+T on tumor cell killing.The experimental data were analyzed by bilateral t-test.ResultsROC curves and area under the curve(AUC)were used to determine the optimal cutoff points for the peripheral blood-based parameters,based on their utility as markers for the clinical outcome of relapse,cancer-related death.Regarding the LMR in luminal breast cancer patients,5.2 was identified as the optimal cutoff point for distinguishing good prognosis patients from poor prognosis patients(P=0.006).There was no statistically significance in NLR,PLR,AMC,or ALC by ROC analyses.All patients were also divided into either low-(<5.2)or high-(≥5.2)LMR groups.The TILs were correlated with LMR.Kaplan–Meier survival curves analysis showed that the disease-free survival(DFS)in luminal breast cancer patients with a LMR≥5.2 was significantly longer than those with a LMR<5.2(P=0.001).In luminal breast cancer patients with a LMR≥5.2,Kaplan–Meier survival curves demonstrated that the node-negative patients who received CEF regimen showed a little better DFS than those with CE regimen,but the difference was not statistically significant.However,Kaplan-Meier survival curves demonstrated that the DFS in patients received the CEF regimen was significantly longer than the patients received CE regimen in node-positive luminal breast cancer(P<0.05).When the correlation between clinicopathological variables and DFS were analyzed by univariate analysis,LMR[hazard ratio(HR)=0.560;95%CI,0.395–0.793;P=0.001]and lymph node status(HR=1.748;95%CI,1.167–2.620;P=0.007)were significantly related to a higher risk of recurrence.In multivariate analysis,only LMR(HR=0.582;95%CI,0.408–0.831;P=0.003)were proven the independent prognosis factor of survival.The number and function(IL-2,TNF-ɑ,IFN-γ,MIP-1β,CD107ɑ)of CD8~+T cells were obviously elevated in patients with LMR≥5.2.CD8~+T cells killed tumor cells through Fas/Fas L pathway(P<0.05).Fas expressions in 5-FU treated MCF-7/T47D cell lines were higher than that in the control cell lines(P<0.01,P<0.01).The tumor cells treated with 5-FU were co-cultured with different concentrations of CD8~+T cells.The results showed that the sensitivity of 5-FU was dependent on the number of CD8~+T cells.Conclusions(1)LMR is positively correlated with the number of CD8~+T cells in peripheral blood,which is expected to be an adjunct to the prognosis of luminal breast cancer patients.(2)5-FU can enhance the Fas expression in estrogen receptor-positive tumor cells,and luminal node-positive patients with elevated LMR are expected to benefit from 5-FU chemotherapy regimens. |
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