血清Cripto-1在胃癌早期诊断和疗效判断中的初步探讨
|
摘要
目的探讨血清Cripto-1在胃癌诊断和疗效判断中的应用价值,为临床提供参考依据。方法选择2018年1-6月山东大学齐鲁医院收治的胃癌患者79例(胃癌组)、慢性萎缩性胃炎患者42例(慢性萎缩性胃炎组)和体检健康者30例(健康对照组)的血清标本。Cripto-1采用酶联免疫吸附法检测,癌胚抗原(CEA)、糖链抗原724(CA724)采用电化学免疫发光法测定。结果胃癌组、萎缩性胃炎组和健康对照组血清Cripto-1水平中位数(四分位数)分别为3.76(1.42～9.73)μg/L、0.71(0.34～0.86)μg/L、0.36(0.28～0.51)μg/L,差异有统计学意义(P<0.001);其中胃癌组血清Cripto-1水平高于萎缩性胃炎组和健康对照组(均P<0.05);萎缩性胃炎组高于健康对照组(P<0.05)。血清CEA水平中位数(四分位数)3.46(2.15～4.59)U/L和CA724水平3.45(2.44～4.75)U/L仅在胃癌组升高(均P<0.05)。Cripto-1诊断胃癌的受试者工作特征曲线下面积为0.818(95%CI:0.747～0.876),其明显高于CEA和CA724(均P<0.05)。胃癌患者手术后血清Cripto-1水平明显低于手术前水平(P<0.05)。结论血清Cripto-1在胃癌患者中表达升高,经手术治疗后水平发生下降,其诊断价值优于CEA和CA724,是一项潜在的胃癌早期诊断和疗效判断指标。
Objective To explore the value of serum Cripto-1 in the diagnosis and treatment of gastric cancer,and to provide reference for clinical practice.Methods From January to June 2018,serum specimens of 79 patients with gastric cancer(gastric cancer group),42 patients with chronic atrophic gastritis(chronic atrophic gastritis group)and 30 healthy subjects(healthy control group)were collected in Qilu Hospital of Shandong University.Cripto-1 was detected by enzyme-linked immunosorbent assay,and carcinoembryonic antigen(CEA)and sugar chain antigen 724(CA724)were determined by electrochemical immunoluminescence.Results Levels of serum Cripto-1 in gastric cancer group,chronic atrophic gastritis group and healthy control group were 3.76(1.42-9.73)μg/L,0.71(0.34-0.86)μg/L and 0.36(0.28-0.51)μg/L,and a significant difference was observed among 3 groups(P<0.001).Among them,levels of serum Cripto-1 in gastric cancer group were significantly higher than those in chronic atrophic gastritis group and healthy control group(all P<0.05);levels in chronic atrophic gastritis group were significantly higher than those in healthy control group(P<0.05).Levels of serum CEA 3.46(2.15-4.59)U/L and CA724 3.45(2.44-4.75)U/L were only significantly increased in gastric cancer group(P<0.05).The area under the receiver operating characteristic curve for gastritis group diagnosis was 0.818(95%CI:0.747-0.876),significantly higher than CEA and CA724(all P<0.05).For gastric cancer patients,serum Cripto-1 were significantly decreased after operation when compared with levels in pre operation(P<0.05).Conclusion The expression of serum Cripto-1 increased in patients with gastric cancer and decreased after operation.Its diagnostic value is better than that of CEA and CA724.It is a potential index for early diagnosis and evaluation of curative effect of gastric cancer.
Objective To explore the value of serum Cripto-1 in the diagnosis and treatment of gastric cancer,and to provide reference for clinical practice.Methods From January to June 2018,serum specimens of 79 patients with gastric cancer(gastric cancer group),42 patients with chronic atrophic gastritis(chronic atrophic gastritis group)and 30 healthy subjects(healthy control group)were collected in Qilu Hospital of Shandong University.Cripto-1 was detected by enzyme-linked immunosorbent assay,and carcinoembryonic antigen(CEA)and sugar chain antigen 724(CA724)were determined by electrochemical immunoluminescence.Results Levels of serum Cripto-1 in gastric cancer group,chronic atrophic gastritis group and healthy control group were 3.76(1.42-9.73)μg/L,0.71(0.34-0.86)μg/L and 0.36(0.28-0.51)μg/L,and a significant difference was observed among 3 groups(P<0.001).Among them,levels of serum Cripto-1 in gastric cancer group were significantly higher than those in chronic atrophic gastritis group and healthy control group(all P<0.05);levels in chronic atrophic gastritis group were significantly higher than those in healthy control group(P<0.05).Levels of serum CEA 3.46(2.15-4.59)U/L and CA724 3.45(2.44-4.75)U/L were only significantly increased in gastric cancer group(P<0.05).The area under the receiver operating characteristic curve for gastritis group diagnosis was 0.818(95%CI:0.747-0.876),significantly higher than CEA and CA724(all P<0.05).For gastric cancer patients,serum Cripto-1 were significantly decreased after operation when compared with levels in pre operation(P<0.05).Conclusion The expression of serum Cripto-1 increased in patients with gastric cancer and decreased after operation.Its diagnostic value is better than that of CEA and CA724.It is a potential index for early diagnosis and evaluation of curative effect of gastric cancer.
引文
[1]CHEN W,ZHENG R,ZHANG S,et al.Cancer incidence and mortality in China,2013[J].Cancer Lett,2017,401:63-71.
[2]NAMIKAWA T,ISHIDA N,TSUDA S,et al.Successful treatment of liver metastases arising from early gastric cancer achieved clinical complete response by nivolumab[J].Surg Case Rep,2018,4(1):71.
[3]POROKH V,VAHARA P,BRTA T,et al.Soluble Cripto-1induces accumulation of supernumerary centrosomes and formation of aberrant mitoses in human embryonic stem cells[J].Stem Cells Dev,2018,27(16):1077-1084.
[4]SILVA L P,DA SILVA L A B,SEDASSARI B T,et al.Cripto-1is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland[J].Eur Arch Otorhinolaryngol,2018,275(6):1595-1600.
[5]ZHANG H,ZHANG B,GAO L,et al.Clinical significance of cripto-1expression in lung adenocarcinoma[J].Oncotarget,2017,8(45):79087-79098.
[6]LIU Q,CUI X,YU X,et al.Cripto-1acts as a functional marker of cancer stem-like cells and predicts prognosis of the patients in esophageal squamous cell carcinoma[J].Mol Cancer,2017,16(1):81.
[7]WANG J H,WEI W,XU J,et al.Elevated expression of Cripto-1correlates with poor prognosis in hepatocellular carcinoma[J].Oncotarget,2015,6(33):35116-35128.
[8]PARK S W,DO H J,HAN M H,et al.The expression of the embryonic gene Cripto-1is regulated by OCT4in human embryonal carcinoma NCCIT cells[J].FEBS Lett,2018,592(1):24-35.
[9]KLAUZINSKA M,CASTRO N P,RANGEL M C,et al.The multifaceted role of the embryonic gene Cripto-1in cancer,stem cells and epithelial-mesenchymal transition[J].Semin Cancer Biol,2014,29:51-58.
[10]ZHANG Y,MI X,SONG Z,et al.Cripto-1promotes resistance to drug-induced apoptosis by activating the TAK-1/NF-κB/survivin signaling pathway[J].Biomed Pharmacother,2018,104:729-737.
[11]KALYAN A,CARNEIRO B A,CHANDRA S,et al.Nodal Signaling as a Developmental Therapeutics Target in Oncology[J].Mol Cancer Ther,2017,16(5):787-792.
[12]SHAN Y,LI S.Expression of Cripto-1gene protein and activin-A in human lung adenocarcinoma tissue[J].Pak JPharm Sci,2015,28(2Suppl):739-743.
[13]LO R C,LEUNG C O,CHAN K K,et al.Cripto-1contributes to stemness in hepatocellular carcinoma by stabilizing dishevelled-3and activating Wnt/β-catenin pathway[J].Cell Death Differ,2018,25(8):1426-1441.
[14]LIU Y,QIN Z,YANG K,et al.Cripto-1promotes epithelial-mesenchymal transition in prostate cancer via Wnt/β-catenin signaling[J].Oncol Rep,2017,37(3):1521-1528.
[15]XU C H,CHI C Z,ZHANG Q,et al.Diagnostic and prognostic value of serum Cripto-1in patients with nonsmall cell lung cancer[J].Clin Respir J,2018,12(10):2469-2474.
[16]ZHANG J G,ZHAO J,XIN Y.Significance and relationship between Cripto-1and p-STAT3expression in gastric cancer and precancerous lesions[J].World J Gastroenterol,2010,16(5):571-577.
[2]NAMIKAWA T,ISHIDA N,TSUDA S,et al.Successful treatment of liver metastases arising from early gastric cancer achieved clinical complete response by nivolumab[J].Surg Case Rep,2018,4(1):71.
[3]POROKH V,VAHARA P,BRTA T,et al.Soluble Cripto-1induces accumulation of supernumerary centrosomes and formation of aberrant mitoses in human embryonic stem cells[J].Stem Cells Dev,2018,27(16):1077-1084.
[4]SILVA L P,DA SILVA L A B,SEDASSARI B T,et al.Cripto-1is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland[J].Eur Arch Otorhinolaryngol,2018,275(6):1595-1600.
[5]ZHANG H,ZHANG B,GAO L,et al.Clinical significance of cripto-1expression in lung adenocarcinoma[J].Oncotarget,2017,8(45):79087-79098.
[6]LIU Q,CUI X,YU X,et al.Cripto-1acts as a functional marker of cancer stem-like cells and predicts prognosis of the patients in esophageal squamous cell carcinoma[J].Mol Cancer,2017,16(1):81.
[7]WANG J H,WEI W,XU J,et al.Elevated expression of Cripto-1correlates with poor prognosis in hepatocellular carcinoma[J].Oncotarget,2015,6(33):35116-35128.
[8]PARK S W,DO H J,HAN M H,et al.The expression of the embryonic gene Cripto-1is regulated by OCT4in human embryonal carcinoma NCCIT cells[J].FEBS Lett,2018,592(1):24-35.
[9]KLAUZINSKA M,CASTRO N P,RANGEL M C,et al.The multifaceted role of the embryonic gene Cripto-1in cancer,stem cells and epithelial-mesenchymal transition[J].Semin Cancer Biol,2014,29:51-58.
[10]ZHANG Y,MI X,SONG Z,et al.Cripto-1promotes resistance to drug-induced apoptosis by activating the TAK-1/NF-κB/survivin signaling pathway[J].Biomed Pharmacother,2018,104:729-737.
[11]KALYAN A,CARNEIRO B A,CHANDRA S,et al.Nodal Signaling as a Developmental Therapeutics Target in Oncology[J].Mol Cancer Ther,2017,16(5):787-792.
[12]SHAN Y,LI S.Expression of Cripto-1gene protein and activin-A in human lung adenocarcinoma tissue[J].Pak JPharm Sci,2015,28(2Suppl):739-743.
[13]LO R C,LEUNG C O,CHAN K K,et al.Cripto-1contributes to stemness in hepatocellular carcinoma by stabilizing dishevelled-3and activating Wnt/β-catenin pathway[J].Cell Death Differ,2018,25(8):1426-1441.
[14]LIU Y,QIN Z,YANG K,et al.Cripto-1promotes epithelial-mesenchymal transition in prostate cancer via Wnt/β-catenin signaling[J].Oncol Rep,2017,37(3):1521-1528.
[15]XU C H,CHI C Z,ZHANG Q,et al.Diagnostic and prognostic value of serum Cripto-1in patients with nonsmall cell lung cancer[J].Clin Respir J,2018,12(10):2469-2474.
[16]ZHANG J G,ZHAO J,XIN Y.Significance and relationship between Cripto-1and p-STAT3expression in gastric cancer and precancerous lesions[J].World J Gastroenterol,2010,16(5):571-577.