SOX2/CDX2/HNF4α在结直肠癌中的研究进展
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摘要
<正>结直肠癌是常见的消化道肿瘤之一,资料显示,全球结直肠癌的发病率位居恶性肿瘤第3位,死亡率位居第2位[1]。结直肠癌发病的地域分布差异较大,其中发达地区发病率较高。我国是结直肠癌的低发区,但发病率呈逐年上升趋势,居恶性肿瘤第
引文
[1] Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424.
[2]郑荣寿,孙可欣,张思维,等. 2015年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志,2019,41(1):19-28.
[3]李道娟,李倩,贺宇彤.结直肠癌流行病学趋势[J].肿瘤防治研究,2015,42(3):305-310.
[4] Niu H,Jia Y,Li T,et al. SOX2 inhibition promotes promoter demethylation of CDX2 to facilitate gastric intestinal metaplasia[J]. Dig Dis Sci,2017,62(1):124-132.
[5] Camilo V,Garrido M,Valente P,et al. Differentiation reprogramming in gastric intestinal metaplasia and dysplasia:role of SOX2 and CDX2[J]. Histopathology,2015,66(3):343-350.
[6] Colleypriest BJ,Burke ZD,Griffiths LP,et al. Hnf4alpha is a key gene that can generate columnar metaplasia in oesophageal epithelium[J]. Differentiation,2017,93:39-49.
[7] Sarkar A,Hochedlinger K. The sox family of transcription factors:versatile regulators of stem and progenitor cell fate[J]. Cell Stem Cell,2013,12(1):15-30.
[8]陈尚忠. SOX2在结直肠癌中的表达及意义的初步研究[D].长沙:中南大学,2010:43.
[9]袁杭.结直肠癌中CD44~+/SOX2~+细胞的表达及临床病理学意义[D].兰州:兰州大学,2017:56.
[10]刘清,帖君,薛增福,等.转录因子Oct4、Sox2在结肠癌中的表达及意义[J].现代肿瘤医学,2011,19(2):201-204.
[11] Han X,Fang Xuefeng,Lou Xiaoyan,et al. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients[J]. PLo S One,2012,7(8):e41335-e41344.
[12] Talebi A,Kianersi K,Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue,polyps,and colon adenocarcinoma using immunohistochemical staining[J]. Adv Biomed Res,2015,4:234-241.
[13] Lundberg IV,Lfgren Burstrm A,Edin S,et al. SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer[J]. PLo S One,2014,9(7):e101957-e101965.
[14] Neumann J,Bahr F,Horst D,et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer[J]. BMC Cancer,2011,11:518-525.
[15] Zheng J,Xu L,Pan Y,et al. Sox2 modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway[J]. Oncotarget,2017,8(58):98635-98645.
[16] Takeda K,Mizushima T,Yokoyama Y,et al. Sox2 is associated with cancer stem-like properties in colorectal cancer[J]. Sci Rep,2018,8(1):17639-17448.
[17] Lundberg IV,Edin S,Eklf V,et al. SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2in colorectal cancer[J]. BMC Cancer,2016,16:471-482.
[18] Liu H,Du L,Wen Z,et al. Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the m TOR signaling pathway[J]. Int J Mol Med,2013,32(1):59-66.
[19] Kang JM,Lee BH,Kim N,et al. CDX1 and CDX2 expression in intestinal metaplasia,dysplasia and gastric cancer[J]. J Korean Med Sci,2011,26(5):647-653.
[20] Coskun M,Troelsen JT,Nielsen OH. The role of CDX2 in intestinal homeostasis and inflammation[J]. Biochim Biophys Acta,2011,1812(3):283-289.
[21] He S,Sun XJ,Zheng JB,et al. Recombinant lentivirus with enhanced expression of caudal-related homeobox protein 2 inhibits human colorectal cancer cell proliferation in vitro[J]. Mol Med Rep,2015,12(2):1838-1844.
[22] Yu J,Liu D,Sun X,et al. CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/β-catenin signaling via transactivation of GSK-3βand Axin2 expression[J]. Cell Death Dis,2019,10(1):26-40.
[23] Zhang BY,Jones JC,Briggler AM,et al. Lack of caudal-type homeobox transcription factor 2 expression as a prognostic biomarker in metastatic colorectal cancer[J]. Clin Colorectal Cancer,2017,16(2):124-128.
[24] Bae JM,Lee TH,Cho NY,et al. Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients[J].World J Gastroenterol,2015,21(5):1457-1467.
[25] Dawson H,Galván JA,Helbling M,et al. Possible role of Cdx2in the serrated pathway of colorectal cancer characterized by BRAF mutation,high-level CpG Island methylator phenotype and mismatch repair-deficiency[J]. Int J Cancer,2014,134(10):2342-2351.
[26]刘俊远,黄桂林,李志刚,等. ING4和CDX2在结直肠癌中的表达及其与预后的关系[J].天津医药,2014,42(2):131-134.
[27] Dawson H,Koelzer VH,Lukesch AC,et al. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer[J]. Front Oncol,2013,3:265-271.
[28] Olsen J,Eiholm S,Kirkeby LT,et al. CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer[J]. Exp Mol Pathol,2016,100(1):59-66.
[29]张一山. CDX2及COX2的表达与结直肠癌预后的相关性研究[D].大连:大连医科大学,2017:48.
[30] Reggiani BL,Lionti S,Vitarelli E,et al. Prognostic significance of CDX2 immunoexpression in poorly differentiated clusters of colorectal carcinoma[J]. Virchows Arch,2017,471(6):731-741.
[31] Zheng J,He S,Qi J,et al. Targeted CDX2 expression inhibits aggressive phenotypes of colon cancer cells in vitro and in vivo[J]. Int J Oncol,2017,51(2):478-488.
[32] Hryniuk A,Grainger S,Savory JG,et al. Cdx1 and Cdx2 function as tumor suppressors[J]. J Biol Chem,2014,289(48):33343-33354.
[33] Dalerba P,Sahoo D,Paik S,et al. CDX2 as a prognostic biomarker in stageⅡand stageⅢcolon cancer[J]. N Engl J Med,2016,374(3):211-222.
[34] Shigematsu Y,Inamura K,Yamamoto N,et al. Impact of CDX2expression status on the survival of patients after curative resection for colorectal cancer liver metastasis[J]. BMC Cancer,2018,18(1):980-989.
[35] Sandberg TP,Sweere I,Van Pelt GW,et al. Prognostic value of low CDX2 expression in colorectal cancers with a high stromal content:a short report[J]. Cell Oncol,2019:Epub ahead of print.
[36] Xu W,Zhu Y,Shen W,et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer[J]. J Int Med Res,2019,DOI:10. 1177/0300060518819620.
[37] Tanaka T,Jiang S,Hotta H,et al. Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer[J]. J Pathol,2006,208(5):662-672.
[38] Yao HS,Wang J,Zhang XP,et al. Hepatocyte nuclear factor4alpha suppresses the aggravation of colon carcinoma[J]. Mol Carcinog,2016,55(5):458-472.
[39] Saandi T,Baraille F,Derbal-Wolfrom L,et al. Regulation of the tumor suppressor homeogene Cdx2 by HNF4alpha in intestinal cancer[J]. Oncogene,2013,32(32):3782-3788.
[40] Schwartz B,Algamas-Dimantov A,Hertz R,et al. Inhibition of colorectal cancer by targeting hepatocyte nuclear factor-4alpha[J]. Int J Cancer,2009,124(5):1081-1089.
[41] Darsigny M,Babeu JP,Seidman EG,et al. Hepatocyte nuclear factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species[J]. Cancer Res,2010,70(22):9423-9433.
[42] Oshima T,Kawasaki T,Ohashi R,et al. Downregulated P1 promoter-driven hepatocyte nuclear factor-4alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis[J]. Pathol Int,2007,57(2):82-90.
[43] Babeu JP,Jones C,Geha S,et al. P1 promoter-driven HNF4alpha isoforms are specifically repressed by beta-catenin signaling in colorectal cancer cells[J]. J Cell Sci,2018,131(13):jcs214734-jcs214748.
[44] Chellappa K,Deol P,Evans JR,et al. Opposing roles of nuclear receptor HNF4alpha isoforms in colitis and colitis-associated colon cancer[J]. Elife,2016,5:e10903-e10928.
[45] Vuong LM,Chellappa K,Dhahbi JM,et al. Differential effects of hepatocyte nuclear factor 4alpha isoforms on tumor growth and T-Cell factor 4/AP-1 interactions in human colorectal cancer cells[J]. Mol Cell Biol,2015,35(20):3471-3490.
[2]郑荣寿,孙可欣,张思维,等. 2015年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志,2019,41(1):19-28.
[3]李道娟,李倩,贺宇彤.结直肠癌流行病学趋势[J].肿瘤防治研究,2015,42(3):305-310.
[4] Niu H,Jia Y,Li T,et al. SOX2 inhibition promotes promoter demethylation of CDX2 to facilitate gastric intestinal metaplasia[J]. Dig Dis Sci,2017,62(1):124-132.
[5] Camilo V,Garrido M,Valente P,et al. Differentiation reprogramming in gastric intestinal metaplasia and dysplasia:role of SOX2 and CDX2[J]. Histopathology,2015,66(3):343-350.
[6] Colleypriest BJ,Burke ZD,Griffiths LP,et al. Hnf4alpha is a key gene that can generate columnar metaplasia in oesophageal epithelium[J]. Differentiation,2017,93:39-49.
[7] Sarkar A,Hochedlinger K. The sox family of transcription factors:versatile regulators of stem and progenitor cell fate[J]. Cell Stem Cell,2013,12(1):15-30.
[8]陈尚忠. SOX2在结直肠癌中的表达及意义的初步研究[D].长沙:中南大学,2010:43.
[9]袁杭.结直肠癌中CD44~+/SOX2~+细胞的表达及临床病理学意义[D].兰州:兰州大学,2017:56.
[10]刘清,帖君,薛增福,等.转录因子Oct4、Sox2在结肠癌中的表达及意义[J].现代肿瘤医学,2011,19(2):201-204.
[11] Han X,Fang Xuefeng,Lou Xiaoyan,et al. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients[J]. PLo S One,2012,7(8):e41335-e41344.
[12] Talebi A,Kianersi K,Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue,polyps,and colon adenocarcinoma using immunohistochemical staining[J]. Adv Biomed Res,2015,4:234-241.
[13] Lundberg IV,Lfgren Burstrm A,Edin S,et al. SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer[J]. PLo S One,2014,9(7):e101957-e101965.
[14] Neumann J,Bahr F,Horst D,et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer[J]. BMC Cancer,2011,11:518-525.
[15] Zheng J,Xu L,Pan Y,et al. Sox2 modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway[J]. Oncotarget,2017,8(58):98635-98645.
[16] Takeda K,Mizushima T,Yokoyama Y,et al. Sox2 is associated with cancer stem-like properties in colorectal cancer[J]. Sci Rep,2018,8(1):17639-17448.
[17] Lundberg IV,Edin S,Eklf V,et al. SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2in colorectal cancer[J]. BMC Cancer,2016,16:471-482.
[18] Liu H,Du L,Wen Z,et al. Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the m TOR signaling pathway[J]. Int J Mol Med,2013,32(1):59-66.
[19] Kang JM,Lee BH,Kim N,et al. CDX1 and CDX2 expression in intestinal metaplasia,dysplasia and gastric cancer[J]. J Korean Med Sci,2011,26(5):647-653.
[20] Coskun M,Troelsen JT,Nielsen OH. The role of CDX2 in intestinal homeostasis and inflammation[J]. Biochim Biophys Acta,2011,1812(3):283-289.
[21] He S,Sun XJ,Zheng JB,et al. Recombinant lentivirus with enhanced expression of caudal-related homeobox protein 2 inhibits human colorectal cancer cell proliferation in vitro[J]. Mol Med Rep,2015,12(2):1838-1844.
[22] Yu J,Liu D,Sun X,et al. CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/β-catenin signaling via transactivation of GSK-3βand Axin2 expression[J]. Cell Death Dis,2019,10(1):26-40.
[23] Zhang BY,Jones JC,Briggler AM,et al. Lack of caudal-type homeobox transcription factor 2 expression as a prognostic biomarker in metastatic colorectal cancer[J]. Clin Colorectal Cancer,2017,16(2):124-128.
[24] Bae JM,Lee TH,Cho NY,et al. Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients[J].World J Gastroenterol,2015,21(5):1457-1467.
[25] Dawson H,Galván JA,Helbling M,et al. Possible role of Cdx2in the serrated pathway of colorectal cancer characterized by BRAF mutation,high-level CpG Island methylator phenotype and mismatch repair-deficiency[J]. Int J Cancer,2014,134(10):2342-2351.
[26]刘俊远,黄桂林,李志刚,等. ING4和CDX2在结直肠癌中的表达及其与预后的关系[J].天津医药,2014,42(2):131-134.
[27] Dawson H,Koelzer VH,Lukesch AC,et al. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer[J]. Front Oncol,2013,3:265-271.
[28] Olsen J,Eiholm S,Kirkeby LT,et al. CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer[J]. Exp Mol Pathol,2016,100(1):59-66.
[29]张一山. CDX2及COX2的表达与结直肠癌预后的相关性研究[D].大连:大连医科大学,2017:48.
[30] Reggiani BL,Lionti S,Vitarelli E,et al. Prognostic significance of CDX2 immunoexpression in poorly differentiated clusters of colorectal carcinoma[J]. Virchows Arch,2017,471(6):731-741.
[31] Zheng J,He S,Qi J,et al. Targeted CDX2 expression inhibits aggressive phenotypes of colon cancer cells in vitro and in vivo[J]. Int J Oncol,2017,51(2):478-488.
[32] Hryniuk A,Grainger S,Savory JG,et al. Cdx1 and Cdx2 function as tumor suppressors[J]. J Biol Chem,2014,289(48):33343-33354.
[33] Dalerba P,Sahoo D,Paik S,et al. CDX2 as a prognostic biomarker in stageⅡand stageⅢcolon cancer[J]. N Engl J Med,2016,374(3):211-222.
[34] Shigematsu Y,Inamura K,Yamamoto N,et al. Impact of CDX2expression status on the survival of patients after curative resection for colorectal cancer liver metastasis[J]. BMC Cancer,2018,18(1):980-989.
[35] Sandberg TP,Sweere I,Van Pelt GW,et al. Prognostic value of low CDX2 expression in colorectal cancers with a high stromal content:a short report[J]. Cell Oncol,2019:Epub ahead of print.
[36] Xu W,Zhu Y,Shen W,et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer[J]. J Int Med Res,2019,DOI:10. 1177/0300060518819620.
[37] Tanaka T,Jiang S,Hotta H,et al. Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer[J]. J Pathol,2006,208(5):662-672.
[38] Yao HS,Wang J,Zhang XP,et al. Hepatocyte nuclear factor4alpha suppresses the aggravation of colon carcinoma[J]. Mol Carcinog,2016,55(5):458-472.
[39] Saandi T,Baraille F,Derbal-Wolfrom L,et al. Regulation of the tumor suppressor homeogene Cdx2 by HNF4alpha in intestinal cancer[J]. Oncogene,2013,32(32):3782-3788.
[40] Schwartz B,Algamas-Dimantov A,Hertz R,et al. Inhibition of colorectal cancer by targeting hepatocyte nuclear factor-4alpha[J]. Int J Cancer,2009,124(5):1081-1089.
[41] Darsigny M,Babeu JP,Seidman EG,et al. Hepatocyte nuclear factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species[J]. Cancer Res,2010,70(22):9423-9433.
[42] Oshima T,Kawasaki T,Ohashi R,et al. Downregulated P1 promoter-driven hepatocyte nuclear factor-4alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis[J]. Pathol Int,2007,57(2):82-90.
[43] Babeu JP,Jones C,Geha S,et al. P1 promoter-driven HNF4alpha isoforms are specifically repressed by beta-catenin signaling in colorectal cancer cells[J]. J Cell Sci,2018,131(13):jcs214734-jcs214748.
[44] Chellappa K,Deol P,Evans JR,et al. Opposing roles of nuclear receptor HNF4alpha isoforms in colitis and colitis-associated colon cancer[J]. Elife,2016,5:e10903-e10928.
[45] Vuong LM,Chellappa K,Dhahbi JM,et al. Differential effects of hepatocyte nuclear factor 4alpha isoforms on tumor growth and T-Cell factor 4/AP-1 interactions in human colorectal cancer cells[J]. Mol Cell Biol,2015,35(20):3471-3490.