血清OPN、CXCL13、CXCL16与宫颈癌根治术患者增殖基因表达及术后复发的关系

Relationship between Serum OPN,CXCL13,CXCL16 and Proliferative Gene Expression and Postoperative Recurrence in Patients with Cervical Cancer after Radical Hysterectomy

目的:探讨血清骨桥蛋白(OPN)、CXC亚家族趋化因子(CXCL)13、CXCL16水平与宫颈癌根治术患者增殖基因表达的相关性及与患者术后复发的关系。方法:选取2014年1月至2016年1月期间本院诊治的92例宫颈癌根治术患者(宫颈癌组),64例宫颈上皮内瘤变(CIN)患者作为CIN组,48例健康查体志愿者作为对照组。采用酶联免疫吸附试验检测三组血清OPN、CXCL13、CXCL16水平。采用荧光定量PCR检测宫颈癌组和CIN组组织中增殖基因[血管生成素样蛋白4(ANGPTL4)mRNA、转录因子(FOXP3)mRNA]水平。Pearson相关分析血清OPN、CXCL13、CXCL16和增殖基因ANGPTL4 mRNA、FOXP3 mRNA的相关性。对宫颈癌组患者进行随访,根据随访期复发情况分为复发组39例、未复发组53例。单因素及多因素Logistic回归分析宫颈癌根治术后复发的危险因素。结果:宫颈癌组血清OPN、CXCL13、CXCL16水平显著高于CIN组和对照组(P<0.05)。宫颈癌组病灶中增殖基因ANGPTL4 mRNA、FOXP3 mRNA表达明显高于CIN组(P<0.05)。宫颈癌组血清OPN、CXCL13、CXCL16水平与增殖基因ANGPTL4 mRNA、FOXP3 mRNA表达均呈显著正相关(P<0.05)。随访过程中,出现复发患者39例,复发率为42.39%(39/92)。复发与未复发组患者在FIGO分期、组织学分级、浸润深度、淋巴结转移,血清OPN、CXCL13、CXCL16水平之间,差异具有显著性(P<0.05)。FIGO分期Ⅱ期、组织学分级低分化、浸润深度>1/2、有淋巴结转移、血清OPN≥3.65 ng/mL、血清CXCL13≥191.63 pg/mL、血清CXCL16≥119.46 pg/mL是宫颈癌患者根治术后复发的危险因素(P<0.05)。结论:血清OPN、CXCL13、CXCL16水平与宫颈癌增殖基因表达呈正相关,血清OPN、CXCL13、CXCL16高表达是宫颈癌根治术后复发的危险因素。

Objective:To investigate the correlation between the levels of serum osteopontin(OPN),CXC subfamily chemokine(CXCL)13 and CXCL16 and proliferative gene expression of cervical cancer after radical operation and their relationship with postoperative recurrence.Methods:92 patients with radical cervical cancer(cervical cancer group),64 patients with cervical intraepithelial neoplasia(CIN)were selected as CIN group and 48 healthy volunteers as control group who underwent radical hysterectomy in our hospital from January 2014 to January 2016 were selected.The levels of serum OPN,CXCL13 and CXCL16 in the three groups were detected by enzyme-linked immunosorbent assay.The levels of proliferating gene[angiopoietin-like protein 4(ANGPTL4)mRNA,transcription factor(FOXP3)mRNA]in cervical cancer group and CIN group were detected by fluorescence quantitative PCR.The correlation between serum OPN,CXCL13,CXCL16 and proliferation gene ANGPTL4 mRNA,FOXP3 mRNA were analyzed by Pearson correlation.The patients in the cervical cancer group were followed up,they were divided into 39 cases in the recurrence group and 53 cases in the non recurrence group according to the recurrence during the follow-up period.Univariate and multivariate logistic regression analysis was used to analyze the risk factors of recurrence after radical resection of cervical cancer.The risk factors of recurrence after radical hysterectomy were analyzed by single factor analysis and multiple logistic regression.Results:The levels of serum OPN,CXCL13 and CXCL16 in cervical cancer group were significantly higher than those in CIN group and control group(P<0.05).The expressions of proliferating gene ANGPTL4 mRNA and Foxp3 mRNA in cervical cancer group were significantly higher than those in CIN group(P<0.05).The levels of serum OPN,CXCL13 and CXCL16 in cervical cancer group were significantly positively correlated with the expression of proliferation gene ANGPTL4 mRNA and Foxp3 mRNA(P<0.05).During the follow-up,39 patients had recurrence,and the recurrence rate was 42.39%(39/92).There were significant differences in FIGO stage,histological grade,depth of invasion,lymph node metastasis,serum OPN,CXCL13 and CXCL16 between recurrent and non recurrent groups(P<0.05).FIGO stageⅡ,histological grade poorly differentiated,depth of invasion>1/2,lymph node metastasis,serum OPN≥3.65 ng/mL,serum CXCL13≥191.63 pg/mL,serum CXCL16≥119.46 pg/mL were the risk factors for recurrence after radical operation of cervical cancer(P<0.05).Conclusion:The levels of serum OPN,CXCL13 and CXCL16 are positively correlated with the expression of proliferative genes in cervical cancer,The high expression of serum OPN,CXCL13 and CXCL16 is a risk factor for recurrence after radical hysterectomy.