黏蛋白1与卵巢癌关系的研究进展_West China Medical Journal

Authors：

 徐敏 ,  陈杰

四川大学华西第二医院妇产科（成都 610041）;

Corresponding author：

陈杰, Email: cjzb@sina.com

Keywords：

黏蛋白1; 卵巢癌; CA125; 靶向治疗

DOI：

10.7507/1002-0179.201600103

Video：

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卵巢癌是女性生殖系统的第二大恶性肿瘤，在各类女性生殖系统恶性肿瘤中病死率居于首位。黏蛋白（MUC）1是近年来引起广泛关注的用于诊断早期卵巢癌的标志物之一。研究发现，MUC可以充当细胞表面受体和传感器，传递信号刺激细胞反应，如细胞增生、分化和凋亡，异常的MUC表达提示卵巢癌的发生和发展。MUC在卵巢上皮性肿瘤是潜在的肿瘤标志物，在卵巢癌的诊断、治疗及预后判断中可能发挥重要作用。MUC1为一种膜结合型MUC，目前关于MUC1和卵巢癌的研究较多，现就MUC1与卵巢癌关系研究进展进行综述。

Citation： 徐敏, 陈杰. 黏蛋白1与卵巢癌关系的研究进展. West China Medical Journal, 2016, 31(2): 384-387. doi: 10.7507/1002-0179.201600103 Copy

1.	JemalA, SiegelR, Xu J, et al. Cancer statisties[J]. CA Cancer J Clin, 2010, 60(13):277-300.
2.	崔恒. 卵巢癌的早期诊断[J]. 中国妇产科临床杂志, 2010, 11(6):403-405.
3.	Bafna S, Kaur S, Batra SK. Membrane-bound mucins:the mechanistic basis for alterations in the growth and survival of cancer cells[J]. Oncogene, 2010, 29(20):2893-2904.
4.	Reis CA, Osorio H, Silva L, et al. Alterations in glycosylation as biomarkers for cancer detection[J]. J Clin Pathol, 2010, 63(4):322-329.
5.	Moore RG, Maclaughlan S. Current clinical use of biomarkers for epithelial ovarian cancer[J]. Curr Opin Oncol, 2010, 22(5):492-497.
6.	Romero I, Bast RC. Minireview:human ovarian cancer:biology, current management, and paths to personalizing therapy[J]. Endocrinology, 2012, 153(4):1593-1602.
7.	Werdelin O, Meldal M, Jensen T. Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells[J]. Proc Natl Acad Sci USA, 2002, 99(15):9611-9613.
8.	Kim D, Jung WH, Koo JS. Expression of MUC1, MUC2, MUC5AC and MUC5B in mucinous lesions of the breast[J]. Pathobiology, 2012, 79(3):144-153.
9.	Quin RJ, Mcguckin MA. Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with changes in cell-cell adhesion[J]. Int J Cancer, 2000, 87(4):499-506.
10.	Dong Y, Walsh MD, Cummings MC, et al. Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours[J]. J Pathol, 1997, 183(3):311-317.
11.	刘颖, 史惠蓉, 魏丽惠, 等. 肿瘤相关粘蛋白MUC1及其同种型MUC1/Y与卵巢上皮性肿瘤关系的研究[J]. 中国实用妇科与产科杂志, 2003, 19(5):26-28.
12.	安锦丹, 王静芬, 程慧, 等. 黏蛋白MUC1、MUC2和MUC5AC在卵巢上皮性肿瘤中的表达及意义[J]. 中华病理学杂志, 2004, 33(5):468-469.
13.	Feng H, Ghazizadeh M, Konishi H, et al. Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas[J]. Jpn J Clin Oncol, 2002, 32(12):525-529.
14.	Wang L, Ma J, Liu F, et al. Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance[J]. Gynecol Oncol, 2007, 105(3):695-702.
15.	Catharina HE, Frings PH. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer[J]. Histopathology, 2010, 57(4):597-606.
16.	Chauhan SC, Singh AP, Ruiz F, et al. Aberrant expression of MUC4 in ovarian carcinoma:diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)[J]. Mod Pathol, 2006, 19(10):1386-1394.
17.	Van Elssen CH, Frings PW, Bot FJ, et al. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer[J]. Histopathology, 2010, 57(4):597-606.
18.	Singh AP, Senapati S, Ponnusamy MP, et al. Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer[J]. Lancet Oncol, 2008, 9(11):1076-1085.
19.	Deng J, Wang L, Chen H, et al. The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression[J]. Cancer Metastasis Rev, 2013, 32(3/4):535-551.
20.	Jeschke U, Wiest I, Schumacher AL, et al. Determination of MUC1 in sera of ovarian cancer patients and in sera of patients with benign changes of the ovaries with CA15-3, CA27.29, and PankoMab[J]. Anticancer Res, 2012, 32(5):2185-2189.
21.	Shahbazi-Gahrouei D, Abdolahi M. Detection of MUC1-expressing ovarian cancer by C595 monoclonal antibody-conjugated SPIONs using MR imaging[J]. Sci World J, 2013(2013):609151.
22.	Engelstaedter V, Heublein S, Schumacher AL, et al. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients[J]. BMC Cancer, 2012, 12(15):600.
23.	Zhang D, Gao J, Zhu L, et al. Chemoresistance is associated with MUC1 and Lewisy antigen expression in ovarian epithelial cancers[J]. Int J Mol Sci, 2013, 14(6):11024-11033.
24.	Ricardo S, Marcos-Silva L, Pereira D, et al. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours[J]. Mol Oncol, 2015, 9(2):503-512.
25.	Janssen ML, Pels W, Massuger LF, et al. Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model:Effect of the radionuclide[J]. Int J Gynecol Cancer, 2003, 13(5):607-613.
26.	Dai F, Zhang Y, Zhu X, et al. Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation[J]. Target Oncol, 2012, 7(4):217-225.
27.	Dai F, Zhang Y, Zhu X, et al. The anti-chemoresistant effect and mechanism of MUC1 aptamer-miR-29b chimera in ovarian cancer[J]. Gynecol Oncol, 2013, 131(2):451-459.
28.	Liu N, Zhou C, Zhao J, et al. Reversal of paclitaxel resistance in epithelial ovarian carcinoma cells by a MUC1 aptamer-let-7i chimera[J]. Cancer Invest, 2012, 30(8):577-582.
29.	Mony JT, Zhang L, Ma T, et al. Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model[J]. Cancer Immunol Immunother, 2015, 64(9):1095-1108.
30.	Wang L, Chen H, Liu F, et al. Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer[J]. Cancer Lett, 2011, 300(2):122-133.
31.	Wang L, Chen H, Pourgholami MH, et al. Anti-MUC1 monoclonal antibody (C595) and docetaxel markedly reduce tumor burden and ascites, and prolong survival in an in vivo ovarian cancer model[J]. PLoS One, 2011, 6(9):e24405.
32.	Welinder C, Baldetorp B, Borrebaeck C, et al. A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti-tumor activity[J]. Glycobiology, 2011, 21(8):1097-1107.

1. JemalA, SiegelR, Xu J, et al. Cancer statisties[J]. CA Cancer J Clin, 2010, 60(13):277-300.
2. 崔恒. 卵巢癌的早期诊断[J]. 中国妇产科临床杂志, 2010, 11(6):403-405.
3. Bafna S, Kaur S, Batra SK. Membrane-bound mucins:the mechanistic basis for alterations in the growth and survival of cancer cells[J]. Oncogene, 2010, 29(20):2893-2904.
4. Reis CA, Osorio H, Silva L, et al. Alterations in glycosylation as biomarkers for cancer detection[J]. J Clin Pathol, 2010, 63(4):322-329.
5. Moore RG, Maclaughlan S. Current clinical use of biomarkers for epithelial ovarian cancer[J]. Curr Opin Oncol, 2010, 22(5):492-497.
6. Romero I, Bast RC. Minireview:human ovarian cancer:biology, current management, and paths to personalizing therapy[J]. Endocrinology, 2012, 153(4):1593-1602.
7. Werdelin O, Meldal M, Jensen T. Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells[J]. Proc Natl Acad Sci USA, 2002, 99(15):9611-9613.
8. Kim D, Jung WH, Koo JS. Expression of MUC1, MUC2, MUC5AC and MUC5B in mucinous lesions of the breast[J]. Pathobiology, 2012, 79(3):144-153.
9. Quin RJ, Mcguckin MA. Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with changes in cell-cell adhesion[J]. Int J Cancer, 2000, 87(4):499-506.
10. Dong Y, Walsh MD, Cummings MC, et al. Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours[J]. J Pathol, 1997, 183(3):311-317.
11. 刘颖, 史惠蓉, 魏丽惠, 等. 肿瘤相关粘蛋白MUC1及其同种型MUC1/Y与卵巢上皮性肿瘤关系的研究[J]. 中国实用妇科与产科杂志, 2003, 19(5):26-28.
12. 安锦丹, 王静芬, 程慧, 等. 黏蛋白MUC1、MUC2和MUC5AC在卵巢上皮性肿瘤中的表达及意义[J]. 中华病理学杂志, 2004, 33(5):468-469.
13. Feng H, Ghazizadeh M, Konishi H, et al. Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas[J]. Jpn J Clin Oncol, 2002, 32(12):525-529.
14. Wang L, Ma J, Liu F, et al. Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance[J]. Gynecol Oncol, 2007, 105(3):695-702.
15. Catharina HE, Frings PH. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer[J]. Histopathology, 2010, 57(4):597-606.
16. Chauhan SC, Singh AP, Ruiz F, et al. Aberrant expression of MUC4 in ovarian carcinoma:diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)[J]. Mod Pathol, 2006, 19(10):1386-1394.
17. Van Elssen CH, Frings PW, Bot FJ, et al. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer[J]. Histopathology, 2010, 57(4):597-606.
18. Singh AP, Senapati S, Ponnusamy MP, et al. Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer[J]. Lancet Oncol, 2008, 9(11):1076-1085.
19. Deng J, Wang L, Chen H, et al. The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression[J]. Cancer Metastasis Rev, 2013, 32(3/4):535-551.
20. Jeschke U, Wiest I, Schumacher AL, et al. Determination of MUC1 in sera of ovarian cancer patients and in sera of patients with benign changes of the ovaries with CA15-3, CA27.29, and PankoMab[J]. Anticancer Res, 2012, 32(5):2185-2189.
21. Shahbazi-Gahrouei D, Abdolahi M. Detection of MUC1-expressing ovarian cancer by C595 monoclonal antibody-conjugated SPIONs using MR imaging[J]. Sci World J, 2013(2013):609151.
22. Engelstaedter V, Heublein S, Schumacher AL, et al. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients[J]. BMC Cancer, 2012, 12(15):600.
23. Zhang D, Gao J, Zhu L, et al. Chemoresistance is associated with MUC1 and Lewisy antigen expression in ovarian epithelial cancers[J]. Int J Mol Sci, 2013, 14(6):11024-11033.
24. Ricardo S, Marcos-Silva L, Pereira D, et al. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours[J]. Mol Oncol, 2015, 9(2):503-512.
25. Janssen ML, Pels W, Massuger LF, et al. Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model:Effect of the radionuclide[J]. Int J Gynecol Cancer, 2003, 13(5):607-613.
26. Dai F, Zhang Y, Zhu X, et al. Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation[J]. Target Oncol, 2012, 7(4):217-225.
27. Dai F, Zhang Y, Zhu X, et al. The anti-chemoresistant effect and mechanism of MUC1 aptamer-miR-29b chimera in ovarian cancer[J]. Gynecol Oncol, 2013, 131(2):451-459.
28. Liu N, Zhou C, Zhao J, et al. Reversal of paclitaxel resistance in epithelial ovarian carcinoma cells by a MUC1 aptamer-let-7i chimera[J]. Cancer Invest, 2012, 30(8):577-582.
29. Mony JT, Zhang L, Ma T, et al. Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model[J]. Cancer Immunol Immunother, 2015, 64(9):1095-1108.
30. Wang L, Chen H, Liu F, et al. Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer[J]. Cancer Lett, 2011, 300(2):122-133.
31. Wang L, Chen H, Pourgholami MH, et al. Anti-MUC1 monoclonal antibody (C595) and docetaxel markedly reduce tumor burden and ascites, and prolong survival in an in vivo ovarian cancer model[J]. PLoS One, 2011, 6(9):e24405.
32. Welinder C, Baldetorp B, Borrebaeck C, et al. A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti-tumor activity[J]. Glycobiology, 2011, 21(8):1097-1107.

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