Study on Expression of Prox1 Gene and Relevance with Pathological Grade and Clinical Stage in Patients with Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Hongchun , MA Hai , WANG Yu , CHEN Yunlong , LI Yong .

Department of Hepatobiliary Surgery, Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China;

Corresponding author：

Keywords：

Prospero-related homeobox 1 gene; Primary hepatocellular carcinoma; Edmondson pathological grade; TNM stage; Reverse transcription-PCR

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ObjectiveTo detect the expression of Prox1 (prospero-related homeobox 1) gene in primary hepatocellular carcinoma (HCC), and to analyze the correlation of Prox1 gene expression with pathological grade and clinical stage of HCC. MethodsThe expressions of Prox1 gene in carcinoma tissues and adjacent cancerous tissues in HCC as well as normal liver tissues were detected by semi-quantitative RT-PCR, then the correlation of Prox1 gene expression with HCC pathological grade and clinical stage were analyzed. ResultsThe expression of Prox1 gene in carcinoma tissues (0.243±0.102) and adjacent cancerous liver tissues (0.537±0.235) was significantly lower than that in normal liver tissue (0.812±0.372), respectively （ P lt;0.01 or P lt;0.05）. Furthermore, the expression of Prox1 gene in carcinoma tissues was significantly lower than that adjacent cancerous liver tissues (P lt;0.05). The expressions of Prox1 gene in different pathological grade (F=97.950, P lt;0.001) and clinical stage were significantly different (F=228.300, P lt;0.001), and when compared with each other, the differences of pathological grade and clinical stage were also significant (P lt;0.001 or P lt;0.01). The expressions of Prox1 gene in HCC carcinoma tissue were negatively correlated with pathological grade (r=-0.930, P lt;0.01) and clinical stage (r=-0.980, P lt;0.01) of HCC. ConclusionsExpression of Prox1 gene may be related to the initiation and development of HCC, however, that whether Prox1 gene functions as tumor suppressor in HCC needs further investigation.

Citation： YANG Hongchun,MA Hai,WANG Yu,CHEN Yunlong,LI Yong .. Study on Expression of Prox1 Gene and Relevance with Pathological Grade and Clinical Stage in Patients with Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(7): 737-740. doi: Copy

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.	董胜翔, 黄钢. Prox1: 一种与实体肿瘤淋巴结转移相关的细胞内标志 [J]. 肿瘤基础与临床, 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.	张逸群, 叶双梅, 蒋学锋, 等. Prox1在乳腺癌组织中的表达及其与淋巴道转移的关系 [J]. 肿瘤防治研究, 2010, 37(7): 777780.
9.	李力人, 万德森, 潘志忠, 等. 大肠癌VEGFR3与Prox1的相关性研究 [J]. 广东医学, 2005, 26(11): 14881490.
10.	傅仲学, 肖世尧, 王春毅, 等. 转录因子Prox1对大肠癌中淋巴管生成的作用 [J]. 中华消化外科杂志, 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.	李兰双, 胡丽娜. 宫颈癌淋巴道转移模型的建立及Prox1临床意义初探 [J]. 第三军医大学学报, 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在人脑胶质瘤中的表达及意义 [J]. 中国现代医生, 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, 张四洋, 崔泽实. Prox1与淋巴管新生和肿瘤转移的关系 [J]. 国际病理科学与临床杂志, 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. 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. 董胜翔, 黄钢. Prox1: 一种与实体肿瘤淋巴结转移相关的细胞内标志 [J]. 肿瘤基础与临床, 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. 张逸群, 叶双梅, 蒋学锋, 等. Prox1在乳腺癌组织中的表达及其与淋巴道转移的关系 [J]. 肿瘤防治研究, 2010, 37(7): 777780.
9. 李力人, 万德森, 潘志忠, 等. 大肠癌VEGFR3与Prox1的相关性研究 [J]. 广东医学, 2005, 26(11): 14881490.
10. 傅仲学, 肖世尧, 王春毅, 等. 转录因子Prox1对大肠癌中淋巴管生成的作用 [J]. 中华消化外科杂志, 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. 李兰双, 胡丽娜. 宫颈癌淋巴道转移模型的建立及Prox1临床意义初探 [J]. 第三军医大学学报, 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在人脑胶质瘤中的表达及意义 [J]. 中国现代医生, 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, 张四洋, 崔泽实. Prox1与淋巴管新生和肿瘤转移的关系 [J]. 国际病理科学与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on Expression of Prox1 Gene and Relevance with Pathological Grade and Clinical Stage in Patients with Hepatocellular Carcinoma

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