HIF-1α與CDX2在結直腸腺癌組織中的表達及意義△_《中國普外基礎與臨床雜志》

作者：

鄭見寶 ,  孫學軍 , 王煒 , 李守帥 , 任海亮 , 祿韶英 , 石景森

西安交通大學醫學院第一附屬醫院普通外科（西安 710061）;

關鍵詞：

缺氧誘導因子-1α 基因系尾型同源盒基因2 結直腸癌免疫組織化學

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目的探討缺氧誘導因子-1α(HIF-1α)與基因系尾型同源盒基因2(CDX2)蛋白在結直腸腺癌組織中的表達及其與結直腸癌發生、發展的關系，并且研究HIF-1α與CDX2表達之間的相關性。方法收集62例結直腸腺癌及20例正常結直腸組織標本,采用免疫組化SABC法檢測標本中HIF-1α、CDX2蛋白的表達，并采用Spearman等級相關分析分析HIF-1α與CDX2表達之間的相關性。結果在20例正常結直腸黏膜組織中HIF-1α及CDX2蛋白表達陽性率分別為5.0%（1/20）及95.0%（19/20），在62例結直腸腺癌組織中HIF-1α及CDX2蛋白表達陽性率分別為62.9%（39/62）及69.4%（43/62），不同組織中蛋白表達的差異均有統計學意義（P lt;0.05）。結直腸腺癌中，HIF-1α、CDX2蛋白的表達與腫瘤的分化程度、淋巴結轉移及Dukes分期有關（P lt;0.05）； Spearman等級相關分析表明，HIF-1α與CDX2的表達呈負相關（r=－0.293 2，P lt;0.05）。結論 HIF-1α表達上調、CDX2表達下調可能與結直腸腺癌的發生有關，且這兩者間呈負相關。HIF-1α可能參與調控CDX2的表達，進而加速了結直腸癌的惡性進展。

引用本文： 鄭見寶,孫學軍,王煒,李守帥,任海亮,祿韶英,石景森. HIF-1α與CDX2在結直腸腺癌組織中的表達及意義△. 中國普外基礎與臨床雜志, 2010, 17(12): 1265-1269. doi: 復制

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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.
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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.	陳振棟, 吉志武, 安樹才, 等. HIF-1α和MMP-2在低分化胃癌中的表達及與浸潤轉移的關系 [J]. 中國普外基礎與臨床雜志, 2010; 17(2): 187-188.
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9.	郝朗松, 張忠民, 伍曉汀. 腫瘤細胞能量代謝機理的研究進展 [J]. 中國普外基礎與臨床雜志, 2010; 17(1): 97-101.
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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.	韓東, 徐忠法. 結腸癌組織HIF-1α和MMP-9表達及其臨床意義的探討 [J]. 中華腫瘤防治雜志, 2008; 15(23): 1812-1814, 1820.
14.	丁震宇, 梁后杰. HIF-1α與P-gp在結腸癌組織中的表達及意義 [J]. 免疫學雜志, 2008; 24(3): 325-328.
15.	張澤平, 江從慶. HIF-1α、MMP-2在結直腸腺癌組織中的表達及意義 [J]. 實用癌癥雜志, 2008; 23(1): 18-20.
16.	劉勝新, 陳茂平. 大腸腺瘤及腺癌組織中缺氧誘導因子-1α的表達及意義 [J]. 中華消化雜志, 2006; 26(11): 781-782.
17.	秦姣, 龍漢安. 缺氧誘導因子-1α與腫瘤關系的研究進展 [J]. 西部醫學, 2010; 22(7): 1323-1325.
18.	方義湖, 來茂德. 結直腸腫瘤的新標記-CDX2 [J]. 國際遺傳學雜志, 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.	鄭見寶, 孫學軍, 王煒, 等. 缺氧下調結腸癌細胞株CDX2表達的研究 [J]. 中國普通外科雜志, 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. 陳振棟, 吉志武, 安樹才, 等. HIF-1α和MMP-2在低分化胃癌中的表達及與浸潤轉移的關系 [J]. 中國普外基礎與臨床雜志, 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, 張忠民, 伍曉汀. 腫瘤細胞能量代謝機理的研究進展 [J]. 中國普外基礎與臨床雜志, 2010; 17(1): 97-101.
10. 袁源, 鐘竑. 缺氧誘導因子-1結構及功能的研究進展 [J]. 現代生物醫學進展, 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. 韓東, 徐忠法. 結腸癌組織HIF-1α和MMP-9表達及其臨床意義的探討 [J]. 中華腫瘤防治雜志, 2008; 15(23): 1812-1814, 1820.
14. 丁震宇, 梁后杰. HIF-1α與P-gp在結腸癌組織中的表達及意義 [J]. 免疫學雜志, 2008; 24(3): 325-328.
15. 張澤平, 江從慶. HIF-1α、MMP-2在結直腸腺癌組織中的表達及意義 [J]. 實用癌癥雜志, 2008; 23(1): 18-20.
16. 劉勝新, 陳茂平. 大腸腺瘤及腺癌組織中缺氧誘導因子-1α的表達及意義 [J]. 中華消化雜志, 2006; 26(11): 781-782.
17. 秦姣, 龍漢安. 缺氧誘導因子-1α與腫瘤關系的研究進展 [J]. 西部醫學, 2010; 22(7): 1323-1325.
18. 方義湖, 來茂德. 結直腸腫瘤的新標記-CDX2 [J]. 國際遺傳學雜志, 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. 鄭見寶, 孫學軍, 王煒, 等. 缺氧下調結腸癌細胞株CDX2表達的研究 [J]. 中國普通外科雜志, 2010; 19(4): 364-368.

《中國普外基礎與臨床雜志》

HIF-1α與CDX2在結直腸腺癌組織中的表達及意義△

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《中國普外基礎與臨床雜志》

HIF-1α與CDX2在結直腸腺癌組織中的表達及意義△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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