初诊食管癌患者外周血中IL-35水平与疾病进展和预后的关系

Relationship between IL-35 level in peripheral blood and disease progression and prognosis in newly diagnosed esophageal cancer patients

目的检测食管癌(EC)患者外周血中白介素-35(IL-35)水平,并分析其与EC患者临床病理特征和预后的关系。方法选取2014年6月至2019年12月宁波大学附属人民医院收治的68例初诊EC患者为观察组,36例健康志愿者为对照组,收集研究对象的外周血。采用酶联免疫吸附试验(ELISA)方法检测IL-35水平,采用实时荧光定量PCR(qRT-PCR)方法检测P35和EB病毒诱导基因3(EBI3)mRNA水平,并分析IL-35与初诊EC患者临床病理特征和预后的关系。结果初诊EC患者外周血IL-35水平[(104.46±34.78)pg/ml vs(36.35±16.34)pg/ml]和P35 mRNA[(43.79±7.28)vs(20.62±6.76)]、EBI3 mRNA[(18.68±3.86)vs(7.76±2.83)]表达水平显著高于对照组,差异均有统计学意义(P<0.05)。TNM分期Ⅲ~Ⅳ期患者IL-35水平显著高于Ⅰ~Ⅱ期患者[(115.85±28.85)pg/ml vs(96.19±36.27)pg/ml],差异有统计学意义(t=2.479,P<0.05);伴有淋巴结转移EC患者,IL-35水平显著高于无淋巴结转移患者[(119.83±29.74)pg/ml vs(92.23±33.65)pg/ml],差异有统计学意义(t=3.512,P<0.01);28例EC患者经食管癌根治术治疗后,IL-35水平显著下降[(102.65±15.51)pg/ml vs(43.28±12.93)pg/ml;t=11.551,P<0.01]。EC患者IL-35水平与总生存期(OS)呈负相关(r=-0.45,P<0.01);高IL-35水平的EC患者OS明显短于低IL-35水平患者,差异有统计学意义(P<0.01)。单因素分析结果显示:TNM分期、淋巴结转移及IL-35水平是影响EC患者OS的不良因素(P<0.01)。多因素分析结果显示:TNM分期、淋巴结转移和IL-35水平是影响EC患者OS的独立危险因素(P<0.05)。结论IL-35在EC患者中处于高表达状态,并且与肿瘤TNM分期和淋巴结转移有关。

Objective To investigate the relationship between interleukin-35(IL-35)level in peripheral blood and disease progression and prognosis in newly diagnosed esophageal cancer(EC)patients.Methods 68 newly diagnosed EC patients treated in the People's Hospital Affiliated to Ningbo University from June 2014 to December 2019 were selected as the observation group and 36 healthy volun-teers as the control group.Peripheral blood was collected.The levels of IL-35 were detected by enzyme-linked immunosorbent assay(ELISA).P35 and EBI3 mRNA were detected by real-time fluorescence quan-titative polymerase chain reaction(qRT-PCR);the relationship between IL-35 and elinicopathological fea-tures and prognosis of newly diagnosed EC patients was analyzed.Results The levels of IL-35[(104.46±34.78)pg/ml vs(36.35±16.34)pg/ml],P35 mRNA[(43.79±7.28)vs(20.62±6.76)]and EBI3 mRNA[(18.68±3.86)vs(7.76±2.83)]in newly diagnosed EC patients were significantly higher than those in the control group(all P values<0.05).The level of IL-35 in tumor node metastasis(TNM)stage Il-IV patients was significantly higher than that in stage 1-11 patients[(115.85±28.85)pg/ml vs(96.19±36.27)pg/ml],with stistically signifcant diference(1=2.479,P<0.05);The level of IL-35 in EC patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis[(119.83±29.74)pg/ml vs(92.23±33.65)pg/ml],and the difference was also statis-tically significant(1=3.512,P<0.01);After radical esophagectomy,the level of IL-35 in 28 EC patients decreased significantly[(102.65±15.51)pg/ml vs(43.28±12.93)pg/ml;t=11.551,P<0.01].The level of IL-35 in EC patients was negatively correlated with overall survival(OS)(r=-0.45,P<0.01);the OS in EC patients with high level of IL-35 was significanly shorter than that in low level patients(P<0.01).The results of univariate analysis showed that TNM staging,lymph node metastasis and IL-35 level were the unfavorable factors affecting the OS in EC patients(P<0.01).Multivariate analysis showed that TNM staging,lymph node metastasis and IL-35 level were independent risk factors afecting OS in EC pa-tients(P<0.05).Conclusions IL-35 is highly expressed in patients with EC,which closely related to disease stage and lymph node metastasis.