热休克蛋白70及基质金属蛋白酶-7和EHD2蛋白在结直肠癌组织中的表达及意义
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摘要
目的探讨热休克蛋白70(HSP70)、基质金属蛋白酶-7(MMP-7)和EHD2蛋白在结直肠癌(CRC)组织中的表达及意义。方法选择2012年3月至2013年8月齐齐哈尔医学院附属第二医院收治的63例CRC患者的癌组织和癌旁正常组织标本,采用免疫组织化学染色法检测CRC组织和正常结直肠组织中HSP70、MMP-7和EHD2蛋白的表达,并分析HSP70、MMP-7和EHD2蛋白表达与CRC临床病理特征及患者5 a生存率的关系。结果 CRC组织中HSP70、MMP-7、EHD2蛋白阳性表达率分别为66.67%(42/63)、73.02%(46/63)、19.05%(12/63),正常结直肠组织中HSP70、MMP-7、EHD2蛋白阳性表达率分别为11.11%(7/63)、14.29%(9/63)、77.78%(49/63); CRC组织中HSP70、MMP-7阳性表达率显著高于正常结直肠组织(χ~2=40.909、44.173,P<0.05),CRC组织中EHD2阳性表达率显著低于正常结直肠组织(χ~2=43.504,P<0.05)。HSP70、MMP-7和EHD2蛋白表达与CRC患者的性别、年龄、肿瘤直径及肿瘤部位无相关性(P>0.05); HSP70、MMP-7和EHD2蛋白表达与CRC分化程度、Duke分期及淋巴结转移显著相关(P<0.05),CRC分化程度越低、Dukes分期越差及有淋巴结转移,HSP70和MMP-7阳性表达越高,EHD2阳性表达越低。63例患者均获得5 a随访,生存43例(68.3%),病死20例(31.7%)。HSP70阳性表达患者5 a生存率为59.52%(25/42),HSP70阴性表达患者5 a生存率为85.71%(18/21); MMP-7阳性表达患者5 a生存率为60.87%(28/46),MMP-7阴性表达患者5 a生存率为88.24%(15/17); EHD2阳性表达患者5 a生存率为100.00%(12/12),EHD2阴性表达患者5 a生存率为60.78%(31/51); HSP70和MMP-7阳性表达患者5 a生存率低于阴性表达患者(χ~2=4.260、3.902,P<0.05),EHD2阳性表达患者5 a生存率高于阴性表达患者(χ~2=5.893,P<0.05)。结论HSP70、MMP-7和EHD2的表达可能与结直肠癌的发生发展有关,可作为判断结直肠癌预后的指标。
Objective To investigate the expression and significance of heat shock protein 70(HSP70),matrix metalloproteinase-7(MMP-7) and EHD2 in colorectal cancer(CRC) tissues. Methods A total of 63 specimens of CRC tissues and 63 specimens of adjacent normal tissues were collected from the Second Affiliated Hospital of Qiqihar Medical University from March 2012 to August 2013.The expression of HSP70,MMP-7 and EHD2 protein in CRC and normal colorectal tissues were detected by immunohistochemical staining. The relationship between the expression of HSP70,MMP-7,EHD2 protein and the clinicopathological characteristics of CRC and the 5-year survival rate of patients was analyzed. Results The positive expression rate of HSP70,MMP-7 and EHD2 protein in CRC tissues was 66.67%(42/63),73.02%(46/63)and 19.05%(12/63),respectively. The positive expression rate of HSP70,MMP-7 and EHD2 in normal colorectal tissues was11.11%(7/63),14.29%(9/63) and 77.78%(49/63),respectively. The positive expression rate of HSP70 and MMP-7 in CRC tissues was significantly higher than that in normal colorectal tissues(χ~2=40.909,44.173; P<0.05). The positive expression rate of EHD2 in CRC tissues was significantly lower than that in normal colorectal tissues(χ~2=43.504,P<0.05).The expression of HSP70,MMP-7 and EHD2 protein had no significant correlation with the sex,age,tumor diameter and location in CRC patients(P>0.05). The expression of HSP70,MMP-7 and EHD2 protein was significantly correlated with tissue differentiation degree,Duke staging and lymph node metastasis of CRC(P<0.05). With the decrease of tissue differentiation,the worse of Dukes stage and lymph node metastasis,the positive expression of HSP70 and MMP-7 increased,and the positive expression of EHD2 decreased. Sixty-three patients were followed up for 5 years,43 patients of them survived(68.3%) and 20 patients of them died(31.7%). The 5-year survival rate of patients with HSP70 positive expression was59.52%(25/42),and that of patients with HSP70 negative expression was 85.71%(18/21). The 5-year survival rate of patients with MMP-7 positive expression was 60.87%(28/46),and that of patients with MMP-7 negative expression was88.24%(15/17). The 5-year survival rate of patients with EHD2 positive expression was 100.00%(12/12),and that of patients with EHD2 negative expression was 60.78%(31/51). The 5-year survival rate of patients with HSP70 and MMP-7 positive expression was lower than that of patients with negative expression(χ~2=4.260,3.902; P<0.05). The 5-year survival rate of patients with EHD2 positive expression was higher than that of patients with negative expression(χ~2=5.893,P<0.05). Conclusion The expression of HSP70,MMP-7 and EHD2 may be related to the occurrence and development of colorectal cancer,and them can be used as prognostic indicators of colorectal cancer.
Objective To investigate the expression and significance of heat shock protein 70(HSP70),matrix metalloproteinase-7(MMP-7) and EHD2 in colorectal cancer(CRC) tissues. Methods A total of 63 specimens of CRC tissues and 63 specimens of adjacent normal tissues were collected from the Second Affiliated Hospital of Qiqihar Medical University from March 2012 to August 2013.The expression of HSP70,MMP-7 and EHD2 protein in CRC and normal colorectal tissues were detected by immunohistochemical staining. The relationship between the expression of HSP70,MMP-7,EHD2 protein and the clinicopathological characteristics of CRC and the 5-year survival rate of patients was analyzed. Results The positive expression rate of HSP70,MMP-7 and EHD2 protein in CRC tissues was 66.67%(42/63),73.02%(46/63)and 19.05%(12/63),respectively. The positive expression rate of HSP70,MMP-7 and EHD2 in normal colorectal tissues was11.11%(7/63),14.29%(9/63) and 77.78%(49/63),respectively. The positive expression rate of HSP70 and MMP-7 in CRC tissues was significantly higher than that in normal colorectal tissues(χ~2=40.909,44.173; P<0.05). The positive expression rate of EHD2 in CRC tissues was significantly lower than that in normal colorectal tissues(χ~2=43.504,P<0.05).The expression of HSP70,MMP-7 and EHD2 protein had no significant correlation with the sex,age,tumor diameter and location in CRC patients(P>0.05). The expression of HSP70,MMP-7 and EHD2 protein was significantly correlated with tissue differentiation degree,Duke staging and lymph node metastasis of CRC(P<0.05). With the decrease of tissue differentiation,the worse of Dukes stage and lymph node metastasis,the positive expression of HSP70 and MMP-7 increased,and the positive expression of EHD2 decreased. Sixty-three patients were followed up for 5 years,43 patients of them survived(68.3%) and 20 patients of them died(31.7%). The 5-year survival rate of patients with HSP70 positive expression was59.52%(25/42),and that of patients with HSP70 negative expression was 85.71%(18/21). The 5-year survival rate of patients with MMP-7 positive expression was 60.87%(28/46),and that of patients with MMP-7 negative expression was88.24%(15/17). The 5-year survival rate of patients with EHD2 positive expression was 100.00%(12/12),and that of patients with EHD2 negative expression was 60.78%(31/51). The 5-year survival rate of patients with HSP70 and MMP-7 positive expression was lower than that of patients with negative expression(χ~2=4.260,3.902; P<0.05). The 5-year survival rate of patients with EHD2 positive expression was higher than that of patients with negative expression(χ~2=5.893,P<0.05). Conclusion The expression of HSP70,MMP-7 and EHD2 may be related to the occurrence and development of colorectal cancer,and them can be used as prognostic indicators of colorectal cancer.
引文
[1]FABRIZIO D A,GEORGE TJ J R,DUNNE R F,et al.Beyond mic-rosatellite testing:assessment of tumor mutational burden identifies subsets of colorectal cancer who may respond to immune checkpoint inhibition[J].J Gastrointest Oncol,2018,9(4):610-617.
[2]陈晓燕,罗金键.CXCL8在结直肠癌组织中的表达及其临床意义[J].新乡医学院学报,2018,35(6):505-508.
[3]路丽娟,刘明浩,胡文炜,等.血清氨基酸和CEA/CA19-9联合测定对结直肠癌诊断的价值[J].解放军医学杂志,2018,43(8):685-689.
[4]SEO H W,SEO J P,JUNG G.Heat shock protein 70 and heat shock protein 90 synergistically increase hepatitis B viral capsid assembly[J].Biochem Biophys Res Commun,2018,503(4):2892-2898.
[5]VENTO S I,JOUHI L,MOHAMED H,et al.MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma[J].Virchows Arch,2018,472(6):975-981.
[6]KIM Y,KIM M H,JEON S,et al.Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma[J].PLo S One,2017,12(3):e0174737.
[7]邹超世,林英,刘康海,等.多种肿瘤标志物联合检测诊断结直肠癌的临床价值及预后监测研究[J].国际检验医学杂志,2018,39(23):2960-2963.
[8]吕蔡,刘振湘,白志明.人前列腺癌组织中热休克蛋白90、糖蛋白96的表达及意义[J].现代泌尿外科杂志,2016,21(3):226-230.
[9]董鹏飞,邓晓明.非小细胞肺癌患者血清热休克蛋白90α的临床意义研究[J].中国全科医学,2015,18(19):2354-2356,2360.
[10]蓝永洪,解娜,饶朗毓,等.乳腺癌组织中热休克蛋白70和p53表达及相关性[J].中国老年学杂志,2017,37(21):5245-5246.
[11]BLACK J D,REZVANI K.Heat shock protein 70s as potential molecular targets for colon cancer therapeutics[J].Curr Med Chem,2016,23(28):3171-3188.
[12]JUBRAN R,KOCSIS J,GARAM N,et al.Circulating mitochondrial stress 70 protein/mortalin and cytosolic HSP70 in blood:risk indicators in colorectal cancer[J].Int J Cancer,2017,141(11):2329-2335.
[13]JAGADISH N,PARASHAR D,GUPTA N,et al.Heat shock protein70-2(HSP70-2)is a novel therapeutic target for colorectal cancer and is associated with tumor growth[J].BMC Cancer,2016,16(7):561.
[14]URUSHIBARA F,SHIOZAWA E,MIYACHI H,et al.Expression of matrix metalloproteinase-7 correlates with the invasion of T1colorectal carcinoma[J].Oncol Lett,2018,15(3):3614-3620.
[15]ISHIKAWA T,KIMURA Y,HIRANO H,et al.Matrix metalloproteinase-7 induces homotypic tumor cell aggregation via proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1[J].J Biol Chem,2017,292(50):20769-20784.
[16]JANG B,JUNG H,CHUNG H,et al.Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells[J].Biochem Biophys Res Commun,2016,477(1):47-53.
[17]SUN D W,ZHANG Y Y,QI Y,et al.Prognostic significance of MMP-7 expression in colorectal cancer:a meta-analysis[J].Cancer Epidemiol,2015,39(2):135-142.
[18]BANDAY M Z,SAMEER A S,MIR A H,et al.Matrix metalloproteinase(MMP)-2,-7 and-9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population:a case-control study and a mini review[J].Gene,2016,589(1):81-89.
[19]LV J,FAN N,WANG Y,et al.Identification of differentially expressed proteins of normal and cancerous human colorectal tissues by liquid chromatograph-mass spectrometer based on i TRAQ approach[J].Cancer Invest,2015,33(9):420-428.
[20]SHI Y,LIU X,SUN Y,et al.Decreased expression and prognostic role of EHD2 in human breast carcinoma:correlation with E-cadherin[J].J Mol Histol,2015,46(2):221-231.
[21]YANG X,REN H,YAO L,et al.Role of EHD2 in migration and invasion of human breast cancer cells[J].Tumour Biol,2015,36(5):3717-3726.
[2]陈晓燕,罗金键.CXCL8在结直肠癌组织中的表达及其临床意义[J].新乡医学院学报,2018,35(6):505-508.
[3]路丽娟,刘明浩,胡文炜,等.血清氨基酸和CEA/CA19-9联合测定对结直肠癌诊断的价值[J].解放军医学杂志,2018,43(8):685-689.
[4]SEO H W,SEO J P,JUNG G.Heat shock protein 70 and heat shock protein 90 synergistically increase hepatitis B viral capsid assembly[J].Biochem Biophys Res Commun,2018,503(4):2892-2898.
[5]VENTO S I,JOUHI L,MOHAMED H,et al.MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma[J].Virchows Arch,2018,472(6):975-981.
[6]KIM Y,KIM M H,JEON S,et al.Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma[J].PLo S One,2017,12(3):e0174737.
[7]邹超世,林英,刘康海,等.多种肿瘤标志物联合检测诊断结直肠癌的临床价值及预后监测研究[J].国际检验医学杂志,2018,39(23):2960-2963.
[8]吕蔡,刘振湘,白志明.人前列腺癌组织中热休克蛋白90、糖蛋白96的表达及意义[J].现代泌尿外科杂志,2016,21(3):226-230.
[9]董鹏飞,邓晓明.非小细胞肺癌患者血清热休克蛋白90α的临床意义研究[J].中国全科医学,2015,18(19):2354-2356,2360.
[10]蓝永洪,解娜,饶朗毓,等.乳腺癌组织中热休克蛋白70和p53表达及相关性[J].中国老年学杂志,2017,37(21):5245-5246.
[11]BLACK J D,REZVANI K.Heat shock protein 70s as potential molecular targets for colon cancer therapeutics[J].Curr Med Chem,2016,23(28):3171-3188.
[12]JUBRAN R,KOCSIS J,GARAM N,et al.Circulating mitochondrial stress 70 protein/mortalin and cytosolic HSP70 in blood:risk indicators in colorectal cancer[J].Int J Cancer,2017,141(11):2329-2335.
[13]JAGADISH N,PARASHAR D,GUPTA N,et al.Heat shock protein70-2(HSP70-2)is a novel therapeutic target for colorectal cancer and is associated with tumor growth[J].BMC Cancer,2016,16(7):561.
[14]URUSHIBARA F,SHIOZAWA E,MIYACHI H,et al.Expression of matrix metalloproteinase-7 correlates with the invasion of T1colorectal carcinoma[J].Oncol Lett,2018,15(3):3614-3620.
[15]ISHIKAWA T,KIMURA Y,HIRANO H,et al.Matrix metalloproteinase-7 induces homotypic tumor cell aggregation via proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1[J].J Biol Chem,2017,292(50):20769-20784.
[16]JANG B,JUNG H,CHUNG H,et al.Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells[J].Biochem Biophys Res Commun,2016,477(1):47-53.
[17]SUN D W,ZHANG Y Y,QI Y,et al.Prognostic significance of MMP-7 expression in colorectal cancer:a meta-analysis[J].Cancer Epidemiol,2015,39(2):135-142.
[18]BANDAY M Z,SAMEER A S,MIR A H,et al.Matrix metalloproteinase(MMP)-2,-7 and-9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population:a case-control study and a mini review[J].Gene,2016,589(1):81-89.
[19]LV J,FAN N,WANG Y,et al.Identification of differentially expressed proteins of normal and cancerous human colorectal tissues by liquid chromatograph-mass spectrometer based on i TRAQ approach[J].Cancer Invest,2015,33(9):420-428.
[20]SHI Y,LIU X,SUN Y,et al.Decreased expression and prognostic role of EHD2 in human breast carcinoma:correlation with E-cadherin[J].J Mol Histol,2015,46(2):221-231.
[21]YANG X,REN H,YAO L,et al.Role of EHD2 in migration and invasion of human breast cancer cells[J].Tumour Biol,2015,36(5):3717-3726.