热休克蛋白联合检测在结直肠癌中的诊断价值研究
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摘要
目的通过测定结直肠癌(colorectal cancer,CRC)患者血清热休克蛋白60(HSP60)、癌胚抗原(CEA)、癌抗原242(CA242)、癌抗原724(CA724)及细胞角蛋白19片段抗原(CYFRA21-1)水平变化,探讨最佳检测方案。方法选取2017年6—12月唐山市人民医院收治的CRC患者156例作为CRC组,另选取同期来院体检健康者40例作为正常对照组。收集两组受试者血清,采用酶联免疫吸附双抗体夹心法测定血清HSP60水平,采用电化学发光法测定CEA、CA242、CA724、CYFRA21-1水平;分析CRC组血清HSP60水平与临床特征之间的关系;以病理诊断为金标准,绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析HSP60、CEA、CA242、CA724、CYFRA21-1单项检测及不同联合检测方案对CRC的诊断效能。结果与正常对照组比较,CRC组血清HSP60、CEA、CA242、CA724和CYFRA21-1水平均有所升高,差异均有统计学意义(P<0.05或P<0.01)。CRC组血清HSP60水平与患者性别、年龄、病变部位无关(P> 0.05),TNM分期I+Ⅱ期患者血清HSP60水平低于Ⅲ+Ⅳ期患者,差异有统计学意义(P<0.01)。单项检测诊断效能分析显示,ROC曲线下面积(area under the cure,AUC):HSP60(0.858)> CEA(0.801)> CYFRA21-1(0.793)>CA724(0.708)> CA242(0.706),5种肿瘤标志物单项检测的诊断效能中等,其中HSP60单项检测的诊断效能最高。不同联合检测方案诊断效能分析显示,AUC:HSP60+CEA+CA242+CA724+CYFRA21-1(0.973)> HSP60+CEA(0.924)> CEA+CA242+CA724+CYFRA21-1 (0.916)> CEA+CA242+CA724(0.846),5种肿瘤标志物联合检测诊断效能最高,优于其他组合方案,差异均有统计学意义(P<0.01)。结论HSP60对CRC的诊断及TNM分期有较高的应用价值,HSP60+CEA+CA242+CA724+CYFRA21-1联合检测可显著提高CRC的诊断率。
Objective To investigate the changes of serum heat shock protein 60(HSP60),carcinoembryonic antigen(CEA),carcinogen 242(CA242),carcinogen 724(CA724) and cytokeratin 19 fragment antigen(CYFRA21-1) levels in patients with colorectal cancer(CRC),and to explore the diagnostic value of the optimal protocol for detection of CRC.Methods From June 2017 to December 2017,156 CRC patients who were admitted to Tangshan People's Hospital were enrolled as CRC group and 40 healthy people who underwent physical examination in our hospital during the same period served as normal control group.Serum samples of the two groups were collected and levels of serum HSP60 were determined by enzyme-linked immunosorbent double antibody sandwich method.CEA,CA242,CA724,CYFRA21-1 levels were measured by electrochemiluminescence method.The relationship between serum HSP60 level and clinical features in CRC group was analyzed.In addition,with pathological diagnosis as the gold standard,receiver operating characteristic(ROC) curve was delineated to analyze the diagnostic efficacy of HSP60,CEA,CA242,CA724,and CYFRA21-1 by single test and different combined test schemes for CRC.Results Compared with the normal control group,the serum levels of HSP60,CEA,CA242,CA724 and CYFRA21-1in CRC group were higher(P<0.05 or P<0.01).The level of serum HSP60 in CRC group was not correlated with sex,age and lesion site(P>0.05),but there were significant differences in different TNM stages(P<0.01).Based on analysis of diagnostic efficacy by single detection,the area under ROC curve(AUC) was:HSP60(0.858)>CEA(0.801)>CYFRA21-1(0.793)>CA724(0.708)>CA242(0.706).The diagnostic efficacy of single detection of five tumor markers was moderate,and that of HSP60 was the highest.Analysis of diagnostic efficacy of different combined detection schemes showed AUC:HSP60 + CEA + CA242 + CA724 + CYFR A21-1(0.973)>HSP60 + CEA(0.924)>CEA + CA242 + CA724 + CYFRA21-1(0.916)>CEA + CA242 + CA724(0.846).The combined detection of five tumor markers had the highest diagnostic efficacy,which was superior to other combination schemes(P<0.01).Conclusion HSP60 has a high value in the diagnosis of CRC and TNM staging.The combined detection of HSP60 + CEA + CA242 + CA724 + CYFRA21-1 can significantly improve the diagnostic rate of CRC.
Objective To investigate the changes of serum heat shock protein 60(HSP60),carcinoembryonic antigen(CEA),carcinogen 242(CA242),carcinogen 724(CA724) and cytokeratin 19 fragment antigen(CYFRA21-1) levels in patients with colorectal cancer(CRC),and to explore the diagnostic value of the optimal protocol for detection of CRC.Methods From June 2017 to December 2017,156 CRC patients who were admitted to Tangshan People's Hospital were enrolled as CRC group and 40 healthy people who underwent physical examination in our hospital during the same period served as normal control group.Serum samples of the two groups were collected and levels of serum HSP60 were determined by enzyme-linked immunosorbent double antibody sandwich method.CEA,CA242,CA724,CYFRA21-1 levels were measured by electrochemiluminescence method.The relationship between serum HSP60 level and clinical features in CRC group was analyzed.In addition,with pathological diagnosis as the gold standard,receiver operating characteristic(ROC) curve was delineated to analyze the diagnostic efficacy of HSP60,CEA,CA242,CA724,and CYFRA21-1 by single test and different combined test schemes for CRC.Results Compared with the normal control group,the serum levels of HSP60,CEA,CA242,CA724 and CYFRA21-1in CRC group were higher(P<0.05 or P<0.01).The level of serum HSP60 in CRC group was not correlated with sex,age and lesion site(P>0.05),but there were significant differences in different TNM stages(P<0.01).Based on analysis of diagnostic efficacy by single detection,the area under ROC curve(AUC) was:HSP60(0.858)>CEA(0.801)>CYFRA21-1(0.793)>CA724(0.708)>CA242(0.706).The diagnostic efficacy of single detection of five tumor markers was moderate,and that of HSP60 was the highest.Analysis of diagnostic efficacy of different combined detection schemes showed AUC:HSP60 + CEA + CA242 + CA724 + CYFR A21-1(0.973)>HSP60 + CEA(0.924)>CEA + CA242 + CA724 + CYFRA21-1(0.916)>CEA + CA242 + CA724(0.846).The combined detection of five tumor markers had the highest diagnostic efficacy,which was superior to other combination schemes(P<0.01).Conclusion HSP60 has a high value in the diagnosis of CRC and TNM staging.The combined detection of HSP60 + CEA + CA242 + CA724 + CYFRA21-1 can significantly improve the diagnostic rate of CRC.
引文
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[20]张文利,李洪生,高雪芹.Western blot检测结直肠癌组织热休克蛋白60、70、90α的表达及其临床意义[J].中国病原生物学杂志,2010,5(11):831-833.
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[22]郗群,毛文虹.基于机器学习的结直肠癌血清标志物筛选及早期诊断模型评估[J].解放军预防医学杂志,2016,34(6):879-883,889.
[23]王祥峰.结直肠癌患者血清及粪便中热休克蛋白60检测的临床意义[D].第三军医大学,2007.
[24]曾龙飞,田刚,姚健.Logistic回归和PLS-DA模型评价肿瘤标志物对结肠癌的诊断价值[J].重庆医学,2017,46(8):1038-1041.
[25]陈舒颖,邱芳华,李秋明,等.血清DCD、CA199、CA724和CEA联合检测对大肠癌的诊断价值[J].实用医学杂志,2017,33(15):2482-2485.
[2]杨学全,纪维义.结直肠癌外科诊治近况[J].中国煤炭工业医学杂志,2003,6(9):791-792.
[3]Arnold M,Sierra M S,Laversanne M,et al.Global patterns and trends in colorectal cancer incidence and mortality[J].Gut,2017,66(4):683-691.
[4]Ng S C,Wong S H.Colorectal cancer screening in Asia[J].Br Med Bull,2013,105:29-42.
[5]田正凤,陈洪,翟爱军,等.北京云岗地区体检人群结直肠癌机会性筛查结果分析[J].首都医科大学学报,2016,37(1):34-37.
[6]崔龙.晚期结直肠癌术前评估及治疗策略[J].中华消化外科杂志,2013,12(6):409-412.
[7]中国结直肠癌诊疗规范(2015版)[J].中华消化外科杂志,2015,14(10):783-799.
[8]Rappa F,Unti E,Baiamonte P,et al.Different immunohistochemical levels of Hsp60 and Hsp70 in a subset of brain tumors and putative role of Hsp60 in neuroepithelial tumorigenesis[J].Eur J Histochem,2013,57(2):e20.
[9]Kazimirko V K,Kutovoy V V,Bobyk V I,et al.CHAPERONES FUNCTION HSP60 AND HSP90AND THEIR ROLE IN CARDIAC PATHOLOGY[J].Lik Sprava,2014(9-10):19-24.
[10]Ikwegbue P C,Masamba P,Oyinloye B E,et al.Roles of Heat Shock Proteins in Apoptosis,Oxidative Stress,Human Inflammatory Diseases,and Cancer[J].Pharmaceuticals(Basel),2017,11(1):pii:E2.
[11]Tong W W,Tong G H,Kong H,et al.The tumor promoting roles of HSP60 and HIF2αin gastric cancer cells[J].Tumor Biology,2016,37(7):1-6.
[12]Campanella C,D'Anneo A,Marino Gammazza A,et al.The histone deacetylase inhibitor SAHA induces HSP60 nitration and its extracellular release by exosomal vesicles in human lung-derived carcinoma cells[J].Oncotarget,2016,7(20):28849-28867.
[13]Campanella C,Rappa F,Sciume C,et al.Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery[J].Cancer,2015,121(18):3230-3239.
[14]Pace A,Barone G,Lauria A,et al.Hsp60,a novel target for antitumor therapy:structure-function features and prospective drugs design[J].Curr Pharm Des,2013,19(15):2757-2764.
[15]Caruso Bavisotto C,Cappello F,Macario A J L,et al.Exosomal HSP60:a potentially useful biomarker for diagnosis,assessing prognosis,and monitoring response to treatment[J].Expert Rev Mol Diagn,2017,17(9):815-822.
[16]李世龙,张宝,宋扬,等.肿瘤标志物CEA、CA50、CA19-9、CA72-4、CA242及HSP60联合检测在大肠癌诊断中的应用[J].河北医药,2015,37(7):1004-1006.
[17]Reclusa P,Taverna S,Pucci M,et al.Exosomes as diagnostic and predictive biomarkers in lung cancer[J].J Thorac Dis,2017,9(Suppl 13):S1373-S1382.
[18]Whiteside T L.The potential of tumor-derived exosomes for noninvasive cancer monitoring[J].Expert Rev Mol Diagn,2015,15(10):1293-1310.
[19]马中华,丁洁,王科明.外泌体在结肠癌中的研究进展[J].临床肿瘤学杂志,2016,21(12):1126-1131.
[20]张文利,李洪生,高雪芹.Western blot检测结直肠癌组织热休克蛋白60、70、90α的表达及其临床意义[J].中国病原生物学杂志,2010,5(11):831-833.
[21]Kalia M.Biomarkers for personalized oncology:recent advances and future challenges[J].Metabolism,2015,64(3 Suppl 1):S16-S21.
[22]郗群,毛文虹.基于机器学习的结直肠癌血清标志物筛选及早期诊断模型评估[J].解放军预防医学杂志,2016,34(6):879-883,889.
[23]王祥峰.结直肠癌患者血清及粪便中热休克蛋白60检测的临床意义[D].第三军医大学,2007.
[24]曾龙飞,田刚,姚健.Logistic回归和PLS-DA模型评价肿瘤标志物对结肠癌的诊断价值[J].重庆医学,2017,46(8):1038-1041.
[25]陈舒颖,邱芳华,李秋明,等.血清DCD、CA199、CA724和CEA联合检测对大肠癌的诊断价值[J].实用医学杂志,2017,33(15):2482-2485.