胃癌化疗前后血清巨噬细胞抑制因子-1水平的变化及其临床意义
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摘要
目的探讨进展期胃癌化疗前后血清巨噬细胞抑制因子-1(MIC-1)水平的变化及其临床意义。方法回顾性分析2013年1月~2015年1月在丽水市中心医院住院的进展期胃癌患者61例,应用酶联免疫吸附测定双抗体夹心法检测其化疗前、化疗2个周期后血清MIC-1水平,采用电化学发光免疫分析仪检测上述胃癌患者血清标本癌胚抗原(CEA)、糖类抗原(CA199)浓度,分析化疗前后血清肿瘤标志物水平的变化与临床资料的关系。结果化疗后MIC-1、CEA、CA199水平均明显低于化疗前,差异均有统计学意义(P<0.05)。MIC-1水平与临床分期及分化程度相关(P<0.05)。MIC-1联合CEA、CA199三者作为一个肿瘤标志物,化疗前其表达与临床分期、分化程度及化疗疗效相关(P<0.05),与腹水高度相关(P<0.01);化疗后其表达与腹水、分化程度、化疗效果均相关(P<0.01)。结论 MIC-1在诊断进展期胃癌方面有较高的研究价值,同时联合CEA、CA199检测可以更好地评价胃癌患者的化疗效果,对于判定胃癌患者预后及预示复发有一定的预测价值。MIC-1作为一种新的肿瘤标志物具有良好的应用前景及研究价值。
Objective To investigate the changes and the clinical significance of serum macrophage inhibitory cytokine(MIC-1) levels before and after chemotherapy in advanced gastric cancer. Methods The clinical data of 61 patients with advanced gastric cancer admitted to Lishui Central Hospital from January 2013 to January 2015 were retrospective analyzed. Double antibody sandwich ELISA method was applied to detect the serum MIC-1 levels before chemotherapy and after 2 cycles of chemotherapy. The carcinoembryonic antigen(CEA) and cancer antigen-199(CA199) concentration in serum samples of the gastric cancer were detected by electrochemiluminescence immunoassay analyzer. Relationship between the levels of serum tumor marker before and after chemotherapy and the clinical data were analyzed.Results After chemotherapy, the levels of MIC-1, CEA and CA199 were all significantly lower than those of before chemotherapy, with statistically significant differences(P < 0.05). The level of MIC-1 was correlated with the clinical stage and the degree of differentiation, with statistically significant differences(P < 0.05). MIC-1 combined with CEA and CA199 as one tumor marker, before chemotherapy, the expressions were correlated with the clinical stage, the degree of differentiation and the chemotherapy efficacy(P < 0.05), and was highly correlated with ascites(P < 0.01). After chemotherapy, the expressions were highly correlated with ascites, differentiation and chemotherapy efficacy(P < 0.01). Conclusion This study suggests that MIC-1 has high research value in the diagnosis of advanced gastric cancer. MIC-1 combine with CEA and CA199 can better evaluate the chemotherapy efficacy in patients with gastric cancer and has certain prognostic value for determining the prognosis and the occurrence. As a new tumor marker, MIC-1 has good application prospect and research value.
Objective To investigate the changes and the clinical significance of serum macrophage inhibitory cytokine(MIC-1) levels before and after chemotherapy in advanced gastric cancer. Methods The clinical data of 61 patients with advanced gastric cancer admitted to Lishui Central Hospital from January 2013 to January 2015 were retrospective analyzed. Double antibody sandwich ELISA method was applied to detect the serum MIC-1 levels before chemotherapy and after 2 cycles of chemotherapy. The carcinoembryonic antigen(CEA) and cancer antigen-199(CA199) concentration in serum samples of the gastric cancer were detected by electrochemiluminescence immunoassay analyzer. Relationship between the levels of serum tumor marker before and after chemotherapy and the clinical data were analyzed.Results After chemotherapy, the levels of MIC-1, CEA and CA199 were all significantly lower than those of before chemotherapy, with statistically significant differences(P < 0.05). The level of MIC-1 was correlated with the clinical stage and the degree of differentiation, with statistically significant differences(P < 0.05). MIC-1 combined with CEA and CA199 as one tumor marker, before chemotherapy, the expressions were correlated with the clinical stage, the degree of differentiation and the chemotherapy efficacy(P < 0.05), and was highly correlated with ascites(P < 0.01). After chemotherapy, the expressions were highly correlated with ascites, differentiation and chemotherapy efficacy(P < 0.01). Conclusion This study suggests that MIC-1 has high research value in the diagnosis of advanced gastric cancer. MIC-1 combine with CEA and CA199 can better evaluate the chemotherapy efficacy in patients with gastric cancer and has certain prognostic value for determining the prognosis and the occurrence. As a new tumor marker, MIC-1 has good application prospect and research value.
引文
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[13]Huang Y,He Q,Hillman MJ,et al.Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells[J].Cancer Res,2001,61(18):6918-6924.
[14]Yamaguchi K,Lee SH,Eling TE,et al.Identification of nonsteroidal anti-inflammatory drug-activated gene(NAG-1)as a novel downstream target of phosphatidyl inositol3-kinase/AKT/GSK-3beta pathway[J].J Biol Chem,2004,279(48):49617-49623.
[15]Liu T,Bauskin AR,Zaunders J,et al.Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells[J].Cancer Res,2003,63(16):5034-5040.
[16]Macchione E,Epifano O,Stefanini M,et al.Urokinase redistribution from the secreted to the cell-bound fraction in granulosa cells of rat preovulatory follicles[J].Biol Reprod,2000,62(4):895-903.
[17]Kim KK,Lee JJ,Yang Y,et al.Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of Erb B2 in human breast and gastric cancer cells[J].Carcinogenesis,2008,29(4):704-712.
[18]Lee JY,Cho KB,Kim ES,et al.Risk factors for local recurrence after en bloc endoscopic submucosal dissection for early gastric cancer[J].World J Gastrointest Endosc,2016,8(7):330-337.
[19]Zhang N,Lu B.Expression of macrophage inhibitory cytokine-1 in early gastric cancer cases treated using endoscopic mucosal resection and the correlation with prognosis[J].Oncol Lett,2017,14(2):1967-1970.
[20]Mehta RS,Song M,Bezawada N,et al.A prospective study of macrophage inhibitory cytokine-1(MIC-1/GDF 15)and risk of colorectal cancer[J].J Natl Cancer Inst,2014,106(4):dju016.
[21]Liu Y,Wang X,Wang T,et al.Macrophage Inhibitory Cytokine-1(MIC-1)as A Biomarker for Diagnosis and Prognosis of Stage I-II Non-small Cell Lung Cance[J].Chinese J Lung Cancer,2016,19(4):207-215.
[22]Murielle M,Surinder K,Batra.Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer[J].J Cell Physiol,2010,224(3):626-635.
[23]王小兵,付超,田海梅,等.胃癌患者血清中巨噬细胞抑制因子-1的临床价值研究[J].癌症进展,2011,9(4):379-383.
[24]吴佳,杨力,陶伟,等.血清巨噬细胞抑制因子-1检测对胃癌的诊断价值[J].宁夏医科大学学报,2014,36(6):638-640.
[2]Skipworth RJ,Deans DA,Tan BH,et al.Plasma MIC-1correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer[J].Br J Cancer,2010,102(4):665-672.
[3]Baek KE,Yoon SR,Kim JT,et al.Upregulation and secretion of macrophage inhibitory cytokine-1(MIC-1)in gastric cancers[J].Clin Chim Acta.2009,401(1/2):128-133.
[4]Lee DH,Yang Y,Lee SJ,et al.Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system[J].Cancer Res,2003,63(15):4648-4655.
[5]Bosman FT,Carneiro F,Hruban RH,et al.World Health Organization classification of tumours of the digestive system[M].Lyon:IARC Press,2010.
[6]Edge SB,Byrd DR,Compton CC,et al.AJCC Cancer Staging Manual.Colon and rectum[M].7th edition.New York:Springer-Verlag,2010.
[7]Ajani JA,Bentrem DJ,Besh S,et al.Gastric cancer,version2.2013:featured updates to the NCCN Guidelines[J].J Natl Compr Canc Ne,2013,11(5):531-546.
[8]Eisenhauer EA,Therasse P,Bogaerts J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J].Eur J Cancer,2009,45:228-247.
[9]Bootcov MR,Bauskin AR,Valenzuela SM,et al.MIC-1,a novel macrophage inhibitory cytokine,is a divergent member of the TGF-beta superfamily[J].Proc Natl Acad Sci USA,1997,94(21):11514-11519.
[10]管华琴,黄智铭,吴金明,等.巨噬细胞抑制因子1-m RNA在胃癌及癌前病变黏膜组织中的表达及其临床意义[J].中华消化杂志,2008,28(6):405-407.
[11]Yang H,Filipovic,Brown D,et al.Macrophage inhibitory cytokine-1:a novel biomarker for p53 pathway activation[J].Mol Cancer Ther,2003,2(10):1023-1029.
[12]Pang RP,Zhou JG,Zeng ZR,et al.Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3beta/NAG-1 pathway[J].Cancer Lett,2007,251(2):268-277.
[13]Huang Y,He Q,Hillman MJ,et al.Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells[J].Cancer Res,2001,61(18):6918-6924.
[14]Yamaguchi K,Lee SH,Eling TE,et al.Identification of nonsteroidal anti-inflammatory drug-activated gene(NAG-1)as a novel downstream target of phosphatidyl inositol3-kinase/AKT/GSK-3beta pathway[J].J Biol Chem,2004,279(48):49617-49623.
[15]Liu T,Bauskin AR,Zaunders J,et al.Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells[J].Cancer Res,2003,63(16):5034-5040.
[16]Macchione E,Epifano O,Stefanini M,et al.Urokinase redistribution from the secreted to the cell-bound fraction in granulosa cells of rat preovulatory follicles[J].Biol Reprod,2000,62(4):895-903.
[17]Kim KK,Lee JJ,Yang Y,et al.Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of Erb B2 in human breast and gastric cancer cells[J].Carcinogenesis,2008,29(4):704-712.
[18]Lee JY,Cho KB,Kim ES,et al.Risk factors for local recurrence after en bloc endoscopic submucosal dissection for early gastric cancer[J].World J Gastrointest Endosc,2016,8(7):330-337.
[19]Zhang N,Lu B.Expression of macrophage inhibitory cytokine-1 in early gastric cancer cases treated using endoscopic mucosal resection and the correlation with prognosis[J].Oncol Lett,2017,14(2):1967-1970.
[20]Mehta RS,Song M,Bezawada N,et al.A prospective study of macrophage inhibitory cytokine-1(MIC-1/GDF 15)and risk of colorectal cancer[J].J Natl Cancer Inst,2014,106(4):dju016.
[21]Liu Y,Wang X,Wang T,et al.Macrophage Inhibitory Cytokine-1(MIC-1)as A Biomarker for Diagnosis and Prognosis of Stage I-II Non-small Cell Lung Cance[J].Chinese J Lung Cancer,2016,19(4):207-215.
[22]Murielle M,Surinder K,Batra.Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer[J].J Cell Physiol,2010,224(3):626-635.
[23]王小兵,付超,田海梅,等.胃癌患者血清中巨噬细胞抑制因子-1的临床价值研究[J].癌症进展,2011,9(4):379-383.
[24]吴佳,杨力,陶伟,等.血清巨噬细胞抑制因子-1检测对胃癌的诊断价值[J].宁夏医科大学学报,2014,36(6):638-640.