食管鳞状细胞癌118例肿瘤标志物HSP90α联合Cyfra21-1和CEA检测临床意义

Detection and clinical significance of tumor markers HSP90α combined with Cyfra21-1 and CEA in patients with esophageal squamous cell carcinoma

目的目前食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)尚缺乏灵敏度高的诊断标志物,大多数患者确诊时已到中晚期且预后不良。本研究探讨热休克蛋白90α(heat shock protein 90α,HSP90α)、细胞角蛋白片段19抗原21-1(cytokeratin fragment 19antigen 21-1,Cyfra21-1)和癌胚抗原(carcinoembryonic antigen,CEA)联合检测对ESCC患者的诊断价值及其临床意义。方法选取2016-01-06-2018-12-10山东省肿瘤医院血液采集时未接受放化疗及手术治疗的118例ESCC患者为研究对象并采集血样,同期收集33名健康体检者血液标本。采用酶联免疫吸附测定法检测血浆HSP90α表达水平,采用电化学发光法检测血清Cyfra21-1和CEA表达水平。ROC曲线评估3个指标单独或联合检测对ESCC的诊断效能,各指标表达与食管癌患者临床病理因素的关联分析采用χ^2检验。结果 ESCC患者中HSP90α、Cyfra21-1和CEA中位数(四分位间距)分别为62.535(45.190~107.708)、3.365(2.038~4.633)和3.545(2.190~5.000)ng/mL,均高于对照组的48.882(36.190~64.033)、1.970(1.590~2.380)和1.990(1.990~2.635)ng/mL,差异有统计学意义,Z值分别为-3.566、-4.131和-4.829,均P=0。ESCC患者中HSP90α、Cyfra21-1和CEA阳性表达与患者的肿瘤大小、远端转移及TNM分期,差异均有统计学意义,P<0.05。ESCCⅣ期患者HSP90α、Cyfra21-1及CEA表达水平高于Ⅲ期患者,差异有统计学意义,P<0.05。ESCC患者中HSP90α与Cyfra21-1、CEA联合检测双阳性率分别为31.36%和34.75%,表达呈正相关(r=0.23,P=0.012;r=0.397,P=0)。HSP90α与Cyfra21-1、CEA联合检测对ESCC患者的诊断灵敏度为78.0%,特异性为72.8%,曲线下面积为0.862。结论肿瘤标志物HSP90α和Cyfra21-1、CEA在ESCC患者中呈现高表达状况,联合检测能够提高ESCC患者的诊断灵敏性和特异性,3种肿瘤标志物联合检测对于ESCC早期诊断与评估分期有一定价值。

OBJECTIVE At present,esophageal squamous cell carcinoma(ESCC)is lack of highly effective sensitive diagnostic markers.Most of the patients have reached the middle and late stage at the time of diagnosis and poor prognosis.This study was to investigate the diagnostic value and clinical significance of combined detection of heat shock protein90α(HSP90α),cytokeratin fragment 19 antigen 21-1(CYFRA21-1)and carcinoembryonic antigen(CEA)in patients with ESCC.METHODS From January 6,2016 to December 10,2018,118 patients with ESCC who were not treated by radiotherapy,chemotherapy and surgery were selected as the study objects and blood samples were collected.At the same time,33 blood samples of healthy examiners were collected.The content of HSP90αin plasma was determined by enzyme-linked immunosorbent assay(ELISA),Cyfra21-1 and CEA expression level in serum by electro-chemiluminescence assay(ECL).ROC curve was used to evaluate the diagnostic efficacy of ESCC by three indicators alone or in combination.Chi square test was used to analyze the correlation between the expression of each indicator and the clinicopathological factors of esophageal cancer patients.RESULTS The HSP90α,Cyfra21-1 and CEA median(interquartile spacing)was 62.535(45.190-107.708),3.365(2.038-4.633)and 3.545(2.190-5.000)ng/ml,which were higher than 48.882(36.190-64.033),1.970(1.590-2.380)and 1.990(1.990-2.635)ng/ml of the control group,with statistical significance(Z=-3.566,Z=-4.131,Z=-4.829,P=0).The positive expression of HSP90α,Cyfra21-1 and CEA in patients with ESCC was significantly different from the depth of tumor size,distal metastasis and clinical stage(P<0.05).The positive expression of HSP90α,CYFRA21-1 and CEA in patients with ESCC was significantly different from the depth of tumor invasion,lymph node metastasis,distal metastasis and clinical stage(P<0.05).The expression levels of HSP 90α,CYFRA21-1 and CEA in patients with ESCC stageⅣwere significantly higher than those in patients with stageⅢ(P<0.05).The double positive rates of HSP90α,CYFRA21-1 and CEA were 31.4%and 34.7%respectively,and the expression was positively correlated(r=0.23,P=0.012;r=0.397,P=0).The sensitivity,specificity and AUC of H HSP90αcombined with CYFRA21-1 and CEA were 78.0%,72.8%and 0.862 respectively.CONCLUSIONS Tumor markers HSP90α,Cyfra21-1 and CEA are highly expressed in ESCC patients.Combined detection can significantly improve the sensitivity and specificity of diagnosis in ESCC patients.Combined detection of three tumor markers has a certain diagnostic value for early diagnosis and evaluation of staging of esophageal cancer.