| Objective The reasons why we designed this study were to analyze the divergence of immune status between cervical cancer invalids and physique females,and clarify the influence of concurrent chemoradiotherapy on the immune status of patients.Independent risk factors affecting prognosis were further analyzed through follow-up,and markers that could predict prognosis were screened.At the same time,it will lay a foundation for future immunotherapy screening beneficial patients by serological markers.Methods From October 2017 to November 2020,one hundred and forty-four cervical cancer invalids treated firstly in the Department of Radiotherapy,Affiliated Hospital of Inner Mongolia Medical University were distributed as the research group.Collecting the clinical data such as patients’ age,pathological type,differentiation level,maximum tumor diameter,lymph node metastasis,HPV(human papillomavirus)infection,International Federation of Gynecology and Obstetrics stage and antibiotic application.The invalids’ peripheral venous blood was collected before concurrent chemoradiotherapy and within one month after therapy respectively,and preserved the serum at-80℃ after centrifugation at 3500 r/min for 9 minutes.Twenty physique females in the same period served as the control group,and the preparation and preservation methods of specimens were the same as those of the research group.The treatment plan adopts 6MV-X ray,IGRT(Image Guided Radiation Therapy)or TOMO(Tomotherapy)pelvic field or extended field radiotherapy,with brachytherapy of 5-6 Gy/ time,once or twice a week for 4-6 times.Concurrent chemotherapy with cisplatin single or combined with paclitaxel for 4 cycles.After therapy,patients were followed up,follow-up time was from the end of treatment to disease recurrence,metastasis or death.The study endpoint was DFS(Disease Free Survival).The test method to detect s PD-1(soluble Programmed cell death protein 1)and s PD-L1(soluble Programmed cell death 1-ligand 1)was Elisa(Enzyme Linked Immunosorbent assay),and human Th1/Th2 cytokines were measured by flow fluorescence method.Wilcoxon rank sum test was used to compare the immune factors between the research group and the control group.Logistic regression was applied to clarify the independent factors that affect the prognosis,and the ROC(Receiver Operator Characteristic)curve was used to determine the authenticity,sensitiveness and specialty of predictive factors,and the K-M(Kaplan-Meier)curve was used to explore the clinical application value of predictive factors.Results(1)In the research group,the expression of s PD-1,TNF-α(Tumor Necrosis Factor-α),IL-4(Interleukin-4)and IL-6 were higher than those in the control group before concurrent chemoradiotherapy(p < 0.05).(2)After concurrent chemoradiotherapy,the expression of s PD-L1,s PD-1,IL-2,TNF-α,IFN-γ and IL-4were reduced compared with those before therapy(p < 0.05).(3)After concurrent chemoradiotherapy,IL-6 concentration in the poor prognosis group was obviously higher than that in the good prognosis group(p < 0.05).(4)HPV infection situation and using antibiotic during therapy had effects on prognosis(p < 0.05).(5)Age,IL-6level after treatment,and antibiotic use were the adverse factors for DFS.The likelihood of an adverse outcome increased by 7.3% with each additional year of age;For every 1 unit increase in IL-6 concentration after treatment,the likelihood of adverse outcome increased 7.5%.The risk of poor prognosis was 16.38 times higher in those taking antibiotics or having history of intrauterine infection than in those not taking antibiotics,but low-risk or high-risk HPV infection was the protective factors for recurrence or metastasis of cervical cancer(p < 0.05).(6)The sensitivity and specificity of s PD-1,TNF-α,IL-4 and IL-6 in differentiating patients from healthy women before concurrent chemoradiotherapy were(91.00%,93.20%),(57.60%,85.00%),(34.70%,94.60%),(76.40%,90.00%)respectively(p<0.05).(7)IL-6 concentration was measured after the end of concurrent chemoradiotherapy,and the cut-off value for predicting prognosis was 21.15 pg/ ml,sensitivity was 40.60%,specificity was 86.60%,AUC was 0.658,95%CI(0.544-0.773)(p<0.05).(8)After treatment,DFS of patients with IL-6 concentration exceeding the cut-off value was significantly shorter than that of patients with low IL-6 concentration(p < 0.05).Conclusions(1)The immune status of patients with cervical cancer was different from that of healthy women,and concurrent chemoradiotherapy has an effect on the immune status of patients.(2)Age,IL-6 level after treatment and antibiotic use or intrauterine infection were independent factors for recurrence,metastasis and death of cervical cancer.However,HPV positive are protective factors for poor prognosis.(3)After treatment,IL-6 concentration can be used as a biomarker to predict prognosis,and even become a new target of immunotherapy,with good clinical application value. |
PDF Full Text Request