• 南充市中心醫(yī)院肝膽外科（四川南充　637000）;

目的檢測Prox1 (prospero-related homeobox 1)基因在原發(fā)性肝細(xì)胞癌(HCC)中的表達(dá)，探討其與HCC病理學(xué)分級及臨床分期的相關(guān)性。方法 應(yīng)用RT-PCR方法檢測51例肝癌組織、癌旁組織和16例正常肝組織中Prox1基因表達(dá)，并分析其與HCC病理學(xué)分級和臨床分期的相關(guān)性。 結(jié)果Prox1 mRNA在肝癌、癌旁及正常肝組織中均有表達(dá)，但肝癌組織（0.243±0.102）和癌旁組織（0.537±0.235）的表達(dá)量均明顯低于正常肝組織（0.812±0.372），P lt;0.01或P lt;0.05， 且肝癌組織中Prox1 mRNA表達(dá)量又明顯低于癌旁組織（P lt;0.05）。肝癌組織中Prox1 mRNA的表達(dá)量在不同病理學(xué)分級（F=97.950，P lt;0.001）和臨床分期（F=228.300，P lt;0.001）的肝癌組織中差異均有統(tǒng)計學(xué)意義，且各病理學(xué)分級和臨床分期間兩兩比較，差異也均有統(tǒng)計學(xué)意義（P lt;0.001，P lt;0.01）。 Prox1 mRNA表達(dá)與肝癌的病理學(xué)分級（r=-0.930，P lt;0.01）和臨床分期（r=-0.980，P lt;0.01）呈負(fù)相關(guān)。 結(jié)論 Prox1 mRNA表達(dá)可能與HCC的發(fā)生、發(fā)展有關(guān)，然而其是否為HCC的抑癌基因有待進(jìn)一步證實。

引用本文： 楊紅春,馬海,王宇,陳運龍,李永. Prox1基因在原發(fā)性肝細(xì)胞癌中的表達(dá)及其與病理學(xué)分級及臨床分期的相關(guān)性研究. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(7): 737-740. doi: 復(fù)制

1. ElSerag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis [J]. Gastroenterology, 2007, 132(7): 25572576.
2. Wang JS, Huang T, Su J, et al. Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, Peoples Republic of China[J]. Cancer Epidemiol Biomarkers Prev, 2001, 10(2): 143146.
3. Zinovieva RD, Duncan MK, Johnson TR, et al. Structure and chromosomal localization of the human homeobox gene Prox 1[J]. Genomics, 1996, 35(3): 517522.
4. Oliver G, SosaPineda B, Geisendorf S, et al. Prox 1, a prosperorelated homeobox gene expressed during mouse development[J]. Mech Dev, 1993, 44(1): 316.
5. 董勝翔, 黃鋼. Prox1: 一種與實體腫瘤淋巴結(jié)轉(zhuǎn)移相關(guān)的細(xì)胞內(nèi)標(biāo)志 [J]. 腫瘤基礎(chǔ)與臨床, 2007, 20(2): 183184.
6. Kim H, Nguyen VP, Petrova TV, et al. Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature[J]. BMC Dev Biol, 2010, 10： 72.
7. Agarwal B, Saxena R, Morimiya A, et al. Lymphangiogenesis does not occur in breast cancer [J]. Am J Surg Pathol, 2005, 29(11): 14491455.
8. 張逸群, 葉雙梅, 蔣學(xué)鋒, 等. Prox1在乳腺癌組織中的表達(dá)及其與淋巴道轉(zhuǎn)移的關(guān)系 [J]. 腫瘤防治研究, 2010, 37(7): 777780.
9. 李力人, 萬德森, 潘志忠, 等. 大腸癌VEGFR3與Prox1的相關(guān)性研究 [J]. 廣東醫(yī)學(xué), 2005, 26(11): 14881490.
10. 傅仲學(xué), 肖世堯, 王春毅, 等. 轉(zhuǎn)錄因子Prox1對大腸癌中淋巴管生成的作用 [J]. 中華消化外科雜志, 2007, 6(6): 455458.
11. Xuan M, Fang YR, Wato M, et al. Immunohistochemical colocalization of lymphatics and blood vessels in oral squamous cell carcinomas[J]. J Oral Pathol Med, 2005, 34(6): 334339.
12. 李蘭雙, 胡麗娜. 宮頸癌淋巴道轉(zhuǎn)移模型的建立及Prox1臨床意義初探 [J]. 第三軍醫(yī)大學(xué)學(xué)報, 2009, 31(16): 15851588.
13. Yoshimoto T, Takahashi M, Nagayama S, et al. RNA mutations of prox1 detected in human esophageal cancer cells by the shifted termination assay[J]. Biochem Biophys Res Commun, 2007, 359(2): 258262.
14. 王煜, 范益民. Prox1和PCNA在人腦膠質(zhì)瘤中的表達(dá)及意義 [J]. 中國現(xiàn)代醫(yī)生, 2010, 48(22): 12, 11.
15. Shimoda M, Takahashi M, Yoshimoto T, et al. A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma[J]. Clin Cancer Res, 2006, 12(20 Pt 1): 60056011.
16. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies[J]. Cancer， 1954, 7(3): 462503.
17. Greene FL， Page DL， Fleming ID， et al． AJCC Cancer Staging Handbook [M]. 6th edition． New York： SpringerVerleg．Inc．2002： 140150.
18. Papoutsi M, Dudas J, Becker J, et al. Gene regulation by homeobox transcription factor Prox1 in murine hepatoblasts[J]. Cell Tissue Res, 2007, 330(2): 209220.
19. Song KH, Li T, Chiang JY. A Prosperorelated homeodomain protein is a novel coregulator of hepatocyte nuclear factor 4 alpha that regulates the cholesterol 7 alphahydroxylase gene[J]. J Biol Chem, 2006, 281(15): 1008110088.
20. Dudas J, Mansuroglu T, Moriconi F, et al. Altered regulation of Prox1geneexpression in liver tumors[J]. BMC Cancer, 2008, 8: 92.
21. Dudas J, Elmaouhoub A, Mansuroglu T, et al. Prosperorelated homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from “oval cells”[J]. Histochem Cell Biol, 2006, 126(5): 549562.
22. Dudas J, Papoutsi M, Hecht M, et al. The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium[J]. Anat Embryol (Berl), 2004, 208(5): 359366.
23. Wigle JT, Chowdhury K, Gruss P, et al. Prox1 function is crucial for mouse lensfibre elongation[J]. Nat Genet, 1999, 21(3): 318322.
24. 李雯君, 張四洋, 崔澤實. Prox1與淋巴管新生和腫瘤轉(zhuǎn)移的關(guān)系 [J]. 國際病理科學(xué)與臨床雜志, 2010, 21(4): 332336.
25. Nagai H, Li Y, Hatano S, et al. Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies[J]. Genes Chromosomes Cancer, 2003, 38(1): 1321.
  1. 1. ElSerag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis [J]. Gastroenterology, 2007, 132(7): 25572576.
  2. 2. Wang JS, Huang T, Su J, et al. Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, Peoples Republic of China[J]. Cancer Epidemiol Biomarkers Prev, 2001, 10(2): 143146.
  3. 3. Zinovieva RD, Duncan MK, Johnson TR, et al. Structure and chromosomal localization of the human homeobox gene Prox 1[J]. Genomics, 1996, 35(3): 517522.
  4. 4. Oliver G, SosaPineda B, Geisendorf S, et al. Prox 1, a prosperorelated homeobox gene expressed during mouse development[J]. Mech Dev, 1993, 44(1): 316.
  5. 5. 董勝翔, 黃鋼. Prox1: 一種與實體腫瘤淋巴結(jié)轉(zhuǎn)移相關(guān)的細(xì)胞內(nèi)標(biāo)志 [J]. 腫瘤基礎(chǔ)與臨床, 2007, 20(2): 183184.
  6. 6. Kim H, Nguyen VP, Petrova TV, et al. Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature[J]. BMC Dev Biol, 2010, 10： 72.
  7. 7. Agarwal B, Saxena R, Morimiya A, et al. Lymphangiogenesis does not occur in breast cancer [J]. Am J Surg Pathol, 2005, 29(11): 14491455.
  8. 8. 張逸群, 葉雙梅, 蔣學(xué)鋒, 等. Prox1在乳腺癌組織中的表達(dá)及其與淋巴道轉(zhuǎn)移的關(guān)系 [J]. 腫瘤防治研究, 2010, 37(7): 777780.
  9. 9. 李力人, 萬德森, 潘志忠, 等. 大腸癌VEGFR3與Prox1的相關(guān)性研究 [J]. 廣東醫(yī)學(xué), 2005, 26(11): 14881490.
  10. 10. 傅仲學(xué), 肖世堯, 王春毅, 等. 轉(zhuǎn)錄因子Prox1對大腸癌中淋巴管生成的作用 [J]. 中華消化外科雜志, 2007, 6(6): 455458.
  11. 11. Xuan M, Fang YR, Wato M, et al. Immunohistochemical colocalization of lymphatics and blood vessels in oral squamous cell carcinomas[J]. J Oral Pathol Med, 2005, 34(6): 334339.
  12. 12. 李蘭雙, 胡麗娜. 宮頸癌淋巴道轉(zhuǎn)移模型的建立及Prox1臨床意義初探 [J]. 第三軍醫(yī)大學(xué)學(xué)報, 2009, 31(16): 15851588.
  13. 13. Yoshimoto T, Takahashi M, Nagayama S, et al. RNA mutations of prox1 detected in human esophageal cancer cells by the shifted termination assay[J]. Biochem Biophys Res Commun, 2007, 359(2): 258262.
  14. 14. 王煜, 范益民. Prox1和PCNA在人腦膠質(zhì)瘤中的表達(dá)及意義 [J]. 中國現(xiàn)代醫(yī)生, 2010, 48(22): 12, 11.
  15. 15. Shimoda M, Takahashi M, Yoshimoto T, et al. A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma[J]. Clin Cancer Res, 2006, 12(20 Pt 1): 60056011.
  16. 16. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies[J]. Cancer， 1954, 7(3): 462503.
  17. 17. Greene FL， Page DL， Fleming ID， et al． AJCC Cancer Staging Handbook [M]. 6th edition． New York： SpringerVerleg．Inc．2002： 140150.
  18. 18. Papoutsi M, Dudas J, Becker J, et al. Gene regulation by homeobox transcription factor Prox1 in murine hepatoblasts[J]. Cell Tissue Res, 2007, 330(2): 209220.
  19. 19. Song KH, Li T, Chiang JY. A Prosperorelated homeodomain protein is a novel coregulator of hepatocyte nuclear factor 4 alpha that regulates the cholesterol 7 alphahydroxylase gene[J]. J Biol Chem, 2006, 281(15): 1008110088.
  20. 20. Dudas J, Mansuroglu T, Moriconi F, et al. Altered regulation of Prox1geneexpression in liver tumors[J]. BMC Cancer, 2008, 8: 92.
  21. 21. Dudas J, Elmaouhoub A, Mansuroglu T, et al. Prosperorelated homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from “oval cells”[J]. Histochem Cell Biol, 2006, 126(5): 549562.
  22. 22. Dudas J, Papoutsi M, Hecht M, et al. The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium[J]. Anat Embryol (Berl), 2004, 208(5): 359366.
  23. 23. Wigle JT, Chowdhury K, Gruss P, et al. Prox1 function is crucial for mouse lensfibre elongation[J]. Nat Genet, 1999, 21(3): 318322.
  24. 24. 李雯君, 張四洋, 崔澤實. Prox1與淋巴管新生和腫瘤轉(zhuǎn)移的關(guān)系 [J]. 國際病理科學(xué)與臨床雜志, 2010, 21(4): 332336.
  25. 25. Nagai H, Li Y, Hatano S, et al. Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies[J]. Genes Chromosomes Cancer, 2003, 38(1): 1321.