Expression Levels and Clinical Significance of Foxp3 and Interleukin-6 in Multiple Myeloma

Abstract

Objective To investigate the expression levels,relevance and clinical significance of forkhead box protein (Foxp3) and interleukin (IL)-6 in multiple myeloma (MM).Methods From August 2011 to February 2013,a total of 41 MM patients in Shantou Central Hospital were collected into this study,as study group (n=41),including newly-diagnosis group (n=34) and disease progression group (n=7).According to the International Staging System (ISS) criteria,the newly-diagnosis group were divided into stage Ⅰ group (n=3),stage Ⅱ group (n=14) and stage Ⅲ group (n=17).After 4 courses of chemotherapy,38 MM patients could evaluate the efficacy.These patients were classified into after chemotherapy group (n =38).According to the efficacy,the after chemotherapy goup were divided into complete response (CR) group (n =7),partial response (PR) and minimal response (MR) group (n=16),no-change (NC) and progression disease (PD) group (n-=15).A total of 16 healthy individuals who received medical examination in the same period were included into control group (n =16).The study protocol was approved by the Ethical Review Board of Investigation in Human at Shantou Central Hospital.Informed consent was obtained from all participants.The blood specimens from the subjects were collected at the clinical laboratory.Expression levels of Foxp3 and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA).The cilinical data of the subjects were retrospectively analyzed:expression levels of Foxp3 and IL-6 were compared among different ISS stages,efficacy and before and after treatment.The correlation and clinical significance of Foxp3 and IL-6 expression levels in MM were analyzed.Results ① Expression levels of Foxp3 were significantly reduced in MM patients compared with in levels of Foxp3 healthy controls irrespective of treatment (P＜ 0.001),and considerably equal to those in the newly-diagnosis group and after chemotherapy group (P＞ 0.05).Expression levels of IL-6 were significantly higher in MM patients compared with those in healthy controls irrespective of treatment (P＜ 0.001),and considerably equal to those in the newly-diagnosis group and the after chemotherapy group (P＞ 0.05).② Expression levels of Foxp3 were reducing along with the increasing of the ISS stages in the newlydiagnosis group,but the difference wasn't statistically significant (P＞0.05).And the difference in pairwise comparison of different stages either wasn't statistically significant (P＞0.05).Expression levels of IL-6 were elevating along with the increasing of the ISS stages (P＜0.05).And there was a significant difference in IL-6 level between stage Ⅱ and Ⅲ group (P=0.009).③After chemotherapy,the expression levels of Foxp3 were reduced in order of CR group,PR+MR group and NC+PD group(P＜0.05).Foxp3 levels were significantly higher in CR group than those in PR+ MR group and NC+ PD group (P=0.012,0.001),and there was no significant difference those in between PR+MR group and NC+PD group (P＞ 0.05).Expression levels of IL-6 were elevated in order of CR group,PR+MR group and NC+PD group.IL-6 levels in NC+ PD group were significantly higher than those in CR group and PR+ MR group (P＜ 0.001),and there were significant difference in IL-6 levels between PR+MR group and CR group (P=0.028).④ There was a negative correlation between expression levels of Foxp3 and IL-6 in the study group before chemotherapy (R=-0.632,P＜0.01).Conclusions Expression levels of Foxp3 were significantly reduced in MM patients.The dynamic variation of Foxp3 levels may reflect patients' condition,and could be an important predictor of the efficacy.Expression level of IL-6 might contribute to early diagnosis,monitoring the chemotherapy efficacy and disease progression of patients with MM.The correlation between Foxp3 and IL-6 levels may reflect the dynamic balance between the tumor and the host immune response in the pathogenesis of MM. Key words: Multiple myeloma; Forkhead transcription factors; Interleukin-6; Prognosis; T-lymphocytes, regulatory