Expressions of HIF-1α and CDX2 and Its Clinical Pathological Significance in Colorectal Adenocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHENG Jianbao ,  SUN Xuejun , WANG Wei , LI Shoushuai , REN Hailiang , LU Shaoying , SHI Jingsen.

Department of General Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China;

Corresponding author：

SUN Xuejun, Email: sunxy@mail.xjtu.edu.cn

Keywords：

Hypoxia-inducible factor-1α; Caudal homeobox gene 2; Colorectal cancer; Immunohistochemistry

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Objective To investigate the expressions of hypoxia-inducible factor-1α (HIF-1α) and caudal homeobox gene 2 (CDX2) in colorectal adenocarcinoma, and the relationships between them and the clinicopathologic factor of colorectal adenocarcinoma. Methods The expressions of HIF-1α and CDX2 were detected by immunohistochemistry in 62 specimens of colorectal adenocarcinoma and 20 specimens of normal colorectal mucosa tissue. The correlation between the expressions of HIF-1α and CDX2 was analyzed by Spearman rank correlation analysis. Results The positive rates of HIF-1α expression in normal colorectal mucosa tissue and colorectal adenocarcinoma were 5.0% （1/20） and 62.9% （39/62）, CDX2 were 95.0% （19/20） and 69.4% （43/62）, the differences of positive rate between different tissues were significant （P lt;0.05）. In colorectal adenocarcinoma, the expression of HIF-1α or CDX2 was related to tumor differentiation, lymph node metastasis, and Dukes staging (P lt;0.05). There was a negative correlation between HIF-1α and CDX2 expressions in colorectal adenocarcinoma （r=－0.293 2，P lt;0.05）. Conclusions The up-regulation of HIF-1α and down-regulation of CDX2 may be involved in the genesis of colorectal adenocarcinoma， and there is a negative correlation between the two kinds of protein. HIF-1α may participate in modulation of CDX2 expression and lead to accelerate the progression of colorectal carcinoma.

Citation： ZHENG Jianbao,SUN Xuejun,WANG Wei,LI Shoushuai,REN Hailiang,LU Shaoying,SHI Jingsen.. Expressions of HIF-1α and CDX2 and Its Clinical Pathological Significance in Colorectal Adenocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(12): 1265-1269. doi: Copy

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3.	Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas [J]. Am J Surg Pathol, 2003; 27(3): 303-310.
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6.	Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer [J]. Clin Cancer Res, 2009; 15(14): 4665-4673.
7.	陈振栋, 吉志武, 安树才, 等. HIF-1α和MMP-2在低分化胃癌中的表达及与浸润转移的关系 [J]. 中国普外基础与临床杂志, 2010; 17(2): 187-188.
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15.	张泽平, 江从庆. HIF-1α、MMP-2在结直肠腺癌组织中的表达及意义 [J]. 实用癌症杂志, 2008; 23(1): 18-20.
16.	刘胜新, 陈茂平. 大肠腺瘤及腺癌组织中缺氧诱导因子-1α的表达及意义 [J]. 中华消化杂志, 2006; 26(11): 781-782.
17.	秦姣, 龙汉安. 缺氧诱导因子-1α与肿瘤关系的研究进展 [J]. 西部医学, 2010; 22(7): 1323-1325.
18.	方义湖, 来茂德. 结直肠肿瘤的新标记-CDX2 [J]. 国际遗传学杂志, 2006; 29(4): 311-316.
19.	Tanaka S, Saito K, Ito T, et al. CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre-operative biopsy specimens [J]. Oncol Rep, 2007; 18(1): 87-92.
20.	Gross I, Duluc I, Benameur T, et al. The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells [J]. Oncogene, 2008; 27(1): 107-115.
21.	Benahmed F, Gross I, Guenot D, et al. The microenvironment controls CDX2 homeobox gene expression in colorectal cancer cells [J]. Am J Pathol, 2007; 170(2): 733-744.
22.	Bonhomme C, Duluc I, Martin E, et al. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development [J]. Gut, 2003; 52(10): 1465-1471.
23.	Bakaris S, Cetinkaya A, Ezberci F, et al. Expression of homeodomain protein CDX2 in colorectal adenoma and adenocarcinoma [J]. Histol Histopathol, 2008; 23(9): 1043-1047.
24.	Choi BJ, Kim CJ, Cho YG, et al. Altered expression of CDX2 in colorectal cancers [J]. APMIS, 2006; 114(1): 50-54.
25.	Zheng J, Sun X, Wang W, et al. Hypoxia-inducible factor-1alpha modulates the down-regulation of the homeodomain protein CDX2 in colorectal cancer [J]. Oncol Rep, 2010; 24(1): 97-104.
26.	郑见宝, 孙学军, 王炜, 等. 缺氧下调结肠癌细胞株CDX2表达的研究 [J]. 中国普通外科杂志, 2010; 19(4): 364-368.

1. Huang LE, Bunn HF. Hypoxia-inducible factor and its biomedical relevance [J]. J Biol Chem, 2003; 278(22): 19575-19578.
2. Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases [J]. Cancer Res, 1999; 59(22): 5830-5835.
3. Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas [J]. Am J Surg Pathol, 2003; 27(3): 303-310.
4. Grainger S, Savory JG, Lohnes D. Cdx2 regulates patterning of the intestinal epithelium [J]. Dev Biol, 2010; 339(1): 155-165.
5. Mallo GV, Soubeyran P, Lissitzky JC, et al. Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in colon cancer-derived cells [J]. J Biol Chem, 1998; 273(22): 14030-14036.
6. Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer [J]. Clin Cancer Res, 2009; 15(14): 4665-4673.
7. 陈振栋, 吉志武, 安树才, 等. HIF-1α和MMP-2在低分化胃癌中的表达及与浸润转移的关系 [J]. 中国普外基础与临床杂志, 2010; 17(2): 187-188.
8. Koumenis C. ER stress, hypoxia tolerance and tumor progression [J]. Curr Mol Med, 2006; 6(1): 55-69.
9. 郝朗松, 张忠民, 伍晓汀. 肿瘤细胞能量代谢机理的研究进展 [J]. 中国普外基础与临床杂志, 2010; 17(1): 97-101.
10. 袁源, 钟竑. 缺氧诱导因子-1结构及功能的研究进展 [J]. 现代生物医学进展, 2010; 10(5): 961-963.
11. Choi KS, Bae MK, Jeong JW, et al. Hypoxia-induced angiogenesis during carcinogenesis [J]. J Biochem Mol Biol, 2003; 36(1): 120-127.
12. Yasuda S, Arii S, Mori A, et al. Hexokinase Ⅱ and VEGF expression in liver tumors: correlation with hypoxia-inducible factor 1 alpha and its significance [J]. J Hepatol, 2004; 40(1): 117-123.
13. 韩东, 徐忠法. 结肠癌组织HIF-1α和MMP-9表达及其临床意义的探讨 [J]. 中华肿瘤防治杂志, 2008; 15(23): 1812-1814, 1820.
14. 丁震宇, 梁后杰. HIF-1α与P-gp在结肠癌组织中的表达及意义 [J]. 免疫学杂志, 2008; 24(3): 325-328.
15. 张泽平, 江从庆. HIF-1α、MMP-2在结直肠腺癌组织中的表达及意义 [J]. 实用癌症杂志, 2008; 23(1): 18-20.
16. 刘胜新, 陈茂平. 大肠腺瘤及腺癌组织中缺氧诱导因子-1α的表达及意义 [J]. 中华消化杂志, 2006; 26(11): 781-782.
17. 秦姣, 龙汉安. 缺氧诱导因子-1α与肿瘤关系的研究进展 [J]. 西部医学, 2010; 22(7): 1323-1325.
18. 方义湖, 来茂德. 结直肠肿瘤的新标记-CDX2 [J]. 国际遗传学杂志, 2006; 29(4): 311-316.
19. Tanaka S, Saito K, Ito T, et al. CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre-operative biopsy specimens [J]. Oncol Rep, 2007; 18(1): 87-92.
20. Gross I, Duluc I, Benameur T, et al. The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells [J]. Oncogene, 2008; 27(1): 107-115.
21. Benahmed F, Gross I, Guenot D, et al. The microenvironment controls CDX2 homeobox gene expression in colorectal cancer cells [J]. Am J Pathol, 2007; 170(2): 733-744.
22. Bonhomme C, Duluc I, Martin E, et al. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development [J]. Gut, 2003; 52(10): 1465-1471.
23. Bakaris S, Cetinkaya A, Ezberci F, et al. Expression of homeodomain protein CDX2 in colorectal adenoma and adenocarcinoma [J]. Histol Histopathol, 2008; 23(9): 1043-1047.
24. Choi BJ, Kim CJ, Cho YG, et al. Altered expression of CDX2 in colorectal cancers [J]. APMIS, 2006; 114(1): 50-54.
25. Zheng J, Sun X, Wang W, et al. Hypoxia-inducible factor-1alpha modulates the down-regulation of the homeodomain protein CDX2 in colorectal cancer [J]. Oncol Rep, 2010; 24(1): 97-104.
26. 郑见宝, 孙学军, 王炜, 等. 缺氧下调结肠癌细胞株CDX2表达的研究 [J]. 中国普通外科杂志, 2010; 19(4): 364-368.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of HIF-1α and CDX2 and Its Clinical Pathological Significance in Colorectal Adenocarcinoma

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