CEACA M6与MMP-9在口腔鳞癌中的表达与临床意义
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摘要
目的研究癌胚抗原相关粘6(附因子CEACAM6)与基质金属蛋白酶-9(MMP-9)在口腔鳞癌组织中的表达及其临床意义。方法采用免疫组化的方法检测70例口腔鳞癌组织和30例正常口腔黏膜组织中CEACAM6和MMP-9的蛋白表达,分析其与口腔鳞癌临床病理参数的关系及二者的相关性。结果 CEACAM6和MMP-9在口腔鳞癌组织中表达阳性率分别为71.43%(50/70)74.29%(52/70),在正常口腔黏膜组织中表达阳性率分别为16.67%(5/30)、13.33%(4/30)。CEACAM6和MMP-9在口腔鳞癌组织中阳性表达率均高于正常口腔黏膜组织(P<0.05)。高表达的CEACAM6和MMP-9与口腔鳞癌的组织分化程度以及TNM分期有密切相关性(P<0.05),但与患者的性别、年龄、吸烟及肿瘤大小无相关性(P>0.05)。口腔鳞癌组织中CEACAM6与MMP-9的表达呈显著正相关(r=4.712,P<0.05)。结论 CEACAM6和MMP-9在口腔鳞癌中均呈高表达,参与了口腔鳞癌的发生发展,并可能为口腔鳞癌未来阶段的诊断、治疗、预后等提供重要依据。
Objective To investigate the expression and clinical significance of carcinoembryonic antigenassociated adhesion factor6(CEACAM6) and matrix metalloproteinase-9(MMP-9) in oral squamous cell carcinoma.Methods The expressions of CEACAM6 and MMP-9 in 70 oral squamous cell carcinoma tissues and 30 normal oral mucosa tissues were detected by immunohistochemistry. The relationship between CEACAM6 and MMP-9 expression in oral squamous cell carcinoma and the correlation between them were analyzed. Results The positive rates of CEACAM6 and MMP-9 in oral squamous cell carcinoma were 71.43%(50/70) 74.29%(52/70), respectively, and the positive expression rates in normal oral mucosa were 16.67%(5/30), 13.33%(4/30). The positive expression rates of CEACAM6 and MMP-9 in oral squamous cell carcinoma were higher than those in normal oral mucosa(P<0.05). Highly expressed CEACAM6 and MMP-9 were closely related to the degree of tissue differentiation and TNM staging of oral squamous cell carcinoma(P<0.05), but were not associated with gender, age, smoking and tumor size(P>0.05). There was a significant positive correlation between CEACAM6 and MMP-9 expression in oral squamous cell carcinoma(r=4.712, P<0.05). Conclusion CEACAM6 and MMP-9 are highly expressed in oral squamous cell carcinoma, which is involved in the development of oral squamous cell carcinoma and may provide important evidence for the diagnosis, treatment and prognosis of oral squamous cell carcinoma in the future.
Objective To investigate the expression and clinical significance of carcinoembryonic antigenassociated adhesion factor6(CEACAM6) and matrix metalloproteinase-9(MMP-9) in oral squamous cell carcinoma.Methods The expressions of CEACAM6 and MMP-9 in 70 oral squamous cell carcinoma tissues and 30 normal oral mucosa tissues were detected by immunohistochemistry. The relationship between CEACAM6 and MMP-9 expression in oral squamous cell carcinoma and the correlation between them were analyzed. Results The positive rates of CEACAM6 and MMP-9 in oral squamous cell carcinoma were 71.43%(50/70) 74.29%(52/70), respectively, and the positive expression rates in normal oral mucosa were 16.67%(5/30), 13.33%(4/30). The positive expression rates of CEACAM6 and MMP-9 in oral squamous cell carcinoma were higher than those in normal oral mucosa(P<0.05). Highly expressed CEACAM6 and MMP-9 were closely related to the degree of tissue differentiation and TNM staging of oral squamous cell carcinoma(P<0.05), but were not associated with gender, age, smoking and tumor size(P>0.05). There was a significant positive correlation between CEACAM6 and MMP-9 expression in oral squamous cell carcinoma(r=4.712, P<0.05). Conclusion CEACAM6 and MMP-9 are highly expressed in oral squamous cell carcinoma, which is involved in the development of oral squamous cell carcinoma and may provide important evidence for the diagnosis, treatment and prognosis of oral squamous cell carcinoma in the future.
引文
1周曾同,刘伟.口腔癌前病变的癌变风险预测.实用肿瘤杂志,2015,30(1):4-7.
2 Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics.CA Cancer J Clin,2005,55(2):74-108.
3 Fitzmaurice C,Dicker D,Pain A,et al.The global burden ofcancer.JAMA Oncol,2015,1(4):505-527.
4 Cameron S,de Long LM,Hazar-R,et al.Focal overexpressionof CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis.Mol Cancer,2012,28(11):74.
5 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion toextracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
6 Wallin U,Rothenberger D,Lowry A,et al.CEA-a predictor for pathologic complete response after neoadjuvant therapy for rectal cancer.Dis Colon Rectum,2013,56(7):859-868.
7 Nascimento DD,Durigan RDM,Tibana RA,et al.The response of matrix metalloproteins.Sports Med,2015,45(2):278-309.
8 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
9 Hammarstrom S.The carcinoembryonic antigen(CEA)fami-ly:structures suggested functions and expression in normal and malignant tissues.Semin Cancer Biol,1999,9(2):67-81.
10 Barnett T,Goebel SJ,Nothdurft MA,et al.Carci-noembryonic antigen family:characterization of c DNAs coding for NCA and CEA and suggestion of nonrandom sequence vari-ation in their conserved loop-domains.Genomics,1988,3(1):59-66.
11 Duxbury MS,Matros E,Clancy T,et al.CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanINlesions.Ann Surg,2005,241(3):491-496.
12 Beauchemin N,Arabzadeh A.Carcinoembryoni cantigen-related cell adhesion molecules(CEACAMs)in cancer progression and metastasis.Cancer Metastasis Rev,2013,32(5):643-671.
13 Chapin C,Bailey NA,Gonzales LW,et al.Distribution andsurfactant association of carcinoembryonic cell adhesion molecule 6 in human lung.Am J Physiol Lung Cell Mol Physiol,2012,302:216-225.
14 Katayama A,Bandoh N,Kishibe K,et al.Expressions of matrixmetalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumormetastases andprognosis.Clin Cancer Res,2004,10(2):634-637.
15 Ieta K,Tanaka F,Utsunomiya T,et al.CEACAM6 gene expression in intrahepatic cholangiocarcinoma.Br J Cancer,2006,95(2):532-540.
16 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
17 Chen J,Li Q,An Y,et al.CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer.Int J Oncol,2013,43(2):877-885.
18 Gebauer F,Wicklein D,Horst J,et al.Carcinoembryoni cantigen-related cell adhesion molecules(CEACAM)1,5 and 6as biomarkers in pancreatic cancer.PLo S One,2014,9(11):e113023.
19 Zang M,Zhang B,Zhang Y,et al.CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelialmesenchymal transition via PI3K/AKT signaling pathway.PLo S One,2014,9(11):e112908.
2 Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics.CA Cancer J Clin,2005,55(2):74-108.
3 Fitzmaurice C,Dicker D,Pain A,et al.The global burden ofcancer.JAMA Oncol,2015,1(4):505-527.
4 Cameron S,de Long LM,Hazar-R,et al.Focal overexpressionof CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis.Mol Cancer,2012,28(11):74.
5 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion toextracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
6 Wallin U,Rothenberger D,Lowry A,et al.CEA-a predictor for pathologic complete response after neoadjuvant therapy for rectal cancer.Dis Colon Rectum,2013,56(7):859-868.
7 Nascimento DD,Durigan RDM,Tibana RA,et al.The response of matrix metalloproteins.Sports Med,2015,45(2):278-309.
8 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
9 Hammarstrom S.The carcinoembryonic antigen(CEA)fami-ly:structures suggested functions and expression in normal and malignant tissues.Semin Cancer Biol,1999,9(2):67-81.
10 Barnett T,Goebel SJ,Nothdurft MA,et al.Carci-noembryonic antigen family:characterization of c DNAs coding for NCA and CEA and suggestion of nonrandom sequence vari-ation in their conserved loop-domains.Genomics,1988,3(1):59-66.
11 Duxbury MS,Matros E,Clancy T,et al.CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanINlesions.Ann Surg,2005,241(3):491-496.
12 Beauchemin N,Arabzadeh A.Carcinoembryoni cantigen-related cell adhesion molecules(CEACAMs)in cancer progression and metastasis.Cancer Metastasis Rev,2013,32(5):643-671.
13 Chapin C,Bailey NA,Gonzales LW,et al.Distribution andsurfactant association of carcinoembryonic cell adhesion molecule 6 in human lung.Am J Physiol Lung Cell Mol Physiol,2012,302:216-225.
14 Katayama A,Bandoh N,Kishibe K,et al.Expressions of matrixmetalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumormetastases andprognosis.Clin Cancer Res,2004,10(2):634-637.
15 Ieta K,Tanaka F,Utsunomiya T,et al.CEACAM6 gene expression in intrahepatic cholangiocarcinoma.Br J Cancer,2006,95(2):532-540.
16 Duxbury MS,Ito H,Ashley SW,et al.c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.Biochem Biophys Res Commun,2004,317(1):133-141.
17 Chen J,Li Q,An Y,et al.CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer.Int J Oncol,2013,43(2):877-885.
18 Gebauer F,Wicklein D,Horst J,et al.Carcinoembryoni cantigen-related cell adhesion molecules(CEACAM)1,5 and 6as biomarkers in pancreatic cancer.PLo S One,2014,9(11):e113023.
19 Zang M,Zhang B,Zhang Y,et al.CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelialmesenchymal transition via PI3K/AKT signaling pathway.PLo S One,2014,9(11):e112908.