切换至 "中华医学电子期刊资源库"

中华肝脏外科手术学电子杂志 ›› 2018, Vol. 07 ›› Issue (05) : 426 -430. doi: 10.3877/cma.j.issn.2095-3232.2018.05.018

所属专题: 文献

基础研究

垂体肿瘤转化基因1在肝细胞癌患者中的表达及意义
禤婕滢1, 郭云蔚2,(), 周浩雄2   
  1. 1. 510630 广州,中山大学附属第三医院消化内科;516000 广东省惠州市第三人民医院消化内科
    2. 510630 广州,中山大学附属第三医院消化内科
  • 收稿日期:2018-07-10 出版日期:2018-10-10
  • 通信作者: 郭云蔚
  • 基金资助:
    广东省科技计划项目(2016A020216012); 广州市科技计划项目(201803010018)

Expression and significance of pituitary tumor-transforming gene 1 in patients with hepatocellular carcinoma

Jieying Xuan1, Yunwei Guo2,(), Haoxiong Zhou2   

  1. 1. Department of Gastroenterology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Gastroenterology, the Third People's Hospital of Huizhou, Huizhou 516000, China
    2. Department of Gastroenterology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2018-07-10 Published:2018-10-10
  • Corresponding author: Yunwei Guo
  • About author:
    Corresponding author: Guo Yunwei, Email:
引用本文:

禤婕滢, 郭云蔚, 周浩雄. 垂体肿瘤转化基因1在肝细胞癌患者中的表达及意义[J/OL]. 中华肝脏外科手术学电子杂志, 2018, 07(05): 426-430.

Jieying Xuan, Yunwei Guo, Haoxiong Zhou. Expression and significance of pituitary tumor-transforming gene 1 in patients with hepatocellular carcinoma[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(05): 426-430.

目的

探讨垂体肿瘤转化基因(PTTG)1在肝细胞癌(肝癌)患者肝组织中的表达及意义。

方法

收集中山大学附属第三医院2011年7月至2016年12月确诊的60例肝癌肝切除病理组织标本和2016年6月至12月行肝癌肝切除的15例新鲜肝癌及癌旁组织标本。患者均签署知情同意书,符合医学伦理学规定。以同期因肝血管瘤行肝叶切除的远离血管瘤正常肝组织24例作为正常对照组。免疫组化法、Western blot、RT-PCR染色检测肝癌组织PTTG1表达。PTTG1表达与临床参数的相关性研究采用t检验、Mann-Whitney检验、Kruskal-Wallis检验。率的比较采用χ2检验或Fisher确切概率法。

结果

免疫组化检测显示肝癌和癌旁组织的PTTG1阳性率分别为65%(5%,80%)、3%(2%,6%),明显高于正常对照组织的2%(1%,2%) (Z=6.644,3.876;P<0.05)。Western blot检测显示肝癌组织和癌旁组织的PTTG1相对表达量分别为0.88(0.80,1.78)、0.83(0.53,1.27),明显高于正常对照组织的0.36(0.20,0.62) (Z=3.223,2.605;P<0.05)。RT-PCR检测显示肝癌组织PTTG1相对mRNA表达量为3.09(1.46,4.77),明显高于癌旁组织的0.90(0.62,1.14) (Z=2.605,P<0.05)。肝癌组织PTTG1蛋白表达与组织分化程度有关(χ2=3.849,P<0.05);而癌旁组织PTTG1表达与患者年龄、血清α-L-岩藻糖苷酶水平和肿瘤体积有关(t=2.463,χ2=4.342,6.070;P<0.05)。

结论

PTTG1在肝癌组织中高表达,且PTTG1蛋白表达与肝癌患者α-L-岩藻糖苷酶水平、肿瘤大小、分化程度等相关。

Objective

To investigate the expression and significance of pituitary tumor-transforming gene (PTTG) 1 in the liver tissues of patients with hepatocellular carcinoma (HCC).

Methods

60 HCC pathological tissues of patients undergoing hepatectomy from July 2011 to December 2016 and 15 fresh HCC and para-cancerous tissues of patients undergoing hepatectomy from June to December 2016 in the Third Affiliated Hospital of Sun Yat-sen University were collected. The informed consents of all patients were obtained and the local ethical committee approval was received. Normal liver tissues distant from the hemangioma of 24 patients undergoing lobectomy were collected as normal controls. The expression level of PTTG1 in HCC tissues was detected by immunohistochemistry, Western blot and RT-PCR. The correlation between expression levels of PTTG1 and clinical parameters of patients were analyzed using t test, Mann-Whitney test and Kruskal-Wallis test. The rate comparison was conducted by Chi-square test or Fisher's exact test.

Results

Immunohistochemical staining demonstrated that the positive rate of PTTG1 in HCC tissues and para-cancerous tissues were 65% (5%, 80%) and 3% (2%, 6%), significantly higher than 2% (1%, 2%) in normal control tissues (Z=6.644, 3.876; P<0.05). Western blot revealed that the relative expression levels of PTTG1 in HCC tissues and para-cancerous tissues were 0.88 (0.80, 1.78) and 0.83 (0.53, 1.27), significantly higher than 0.36 (0.20, 0.62) in normal control tissues (Z=3.223, 2.605; P<0.05). RT-PCR showed that the relative expression of PTTG1 mRNA in HCC tissues was 3.09 (1.46, 4.77), significantly higher than 0.90 (0.62, 1.14) in para-cancerous tissues (Z=2.605, P<0.05). In HCC tissues, the expression of PTTG1 protein was correlated with the degree of differentiation (χ2=3.849, P<0.05). The PTTG1 expression in para-cancerous tissues was correlated with age, serum level of α-L-fucosidase and tumor size (t=2.463, χ2=4.342, 6.070; P<0.05).

Conclusions

PTTG1 is highly expressed in HCC tissues. The expression of PTTG1 protein is correlated with the serum level of α-L-fucosidase, tumor size and degree of differentiation in HCC patients.

图1 肝细胞癌、癌旁、正常肝组织PTTG1的表达(免疫组化法×200)
图2 肝细胞癌患者PTTG1的Western blot结果
表1 肝癌癌旁组织PTTG1表达情况与患者临床参数的相关性
[1]
Pei L. Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function[J]. J Biol Chem, 2000, 275(40):31191-31198.
[2]
Solbach C, Roller M, Fellbaum C, et al. PTTG mRNA expression in primary breast cancer: a prognostic marker for lymph node invasion and tumor recurrence[J]. Breast, 2004, 13(1):80-81.
[3]
Romero F, Multon MC, Ramos-Morales F, et al. Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase[J]. Nucleic Acids Res, 2001, 29(6):1300-1307.
[4]
Boelaert K, McCabe CJ, Tannahill LA, et al. Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer[J]. J Clin Endocrinol Metab, 2003, 88(5): 2341-2347.
[5]
Fromowitz FB, Viola MV, Chao S, et al. ras p21 expression in the progression of breast cancer[J]. Hum Pathol, 1987, 18(12):1268-1275.
[6]
Bradshaw C, Kakar SS. Pituitary tumor transforming gene: an important gene in normal cellular functions and tumorigenesis[J]. Histol Histopathol, 2007, 22(2):219-226.
[7]
Haji Amousha MR, Sabetkish N, Heshmat R, et al. Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors[J]. Acta Med Iran, 2015, 53(4):236-241.
[8]
Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification[J]. Semin Liver Dis, 1999, 19(3): 329-338.
[9]
中华人民共和国卫生和计划生育委员会医政医管局.原发性肝癌诊疗规范(2017年版)[J].中华消化外科杂志,2017,16(7):635-647.
[10]
Cao XL, Gao JP, Wang W, et al. Expression of pituitary tumor transforming gene 1 is an independent factor of poor prognosis in localized or locally advanced prostate cancer cases receiving hormone therapy[J]. Asian Pac J Cancer Prev, 2012, 13(7):3083-3088.
[11]
Cho-Rok J, Yoo J, Jang YJ, et al. Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo[J]. Hepatology, 2006, 43(5):1042-1052.
[12]
Liang M, Chen X, Liu W, et al. Role of the pituitary tumor transforming gene 1 in the progression of hepatocellular carcinoma[J]. Cancer Biol Ther, 2011, 11(3): 337-345.
[13]
金中元,程瑞雪,郑长黎,等.PTTG基因表达在原发性肝细胞癌发生中的作用及其机制的初步研究[J].中国现代医学杂志,2004,14(24):37-40, 47.
[14]
Prezant TR, Kadioglu P, Melmed S. An intronless homolog of human proto-oncogene hPTTG is expressed in pituitary tumors: evidence for hPTTG family[J]. J Clin Endocrinol Metab, 1999, 84(3):1149-1152.
[15]
Zhang X, Horwitz GA, Prezant TR, et al. Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)[J]. Mol Endocrinol, 1999, 13(1):156-166.
[16]
Domínguez A, Ramos-Morales F, Romero F, et al. hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. evidence for a transcriptional activation function of hPTTG[J]. Oncogene, 1998, 17(17):2187-2193.
[17]
Fattovich G, Stroffolini T, Zagni I, et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors[J]. Gastroenterology, 2004, 127(5 Suppl 1):S35-50.
[18]
MacDonald DC, Nelson M, Bower M, et al. Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era[J]. World J Gastroenterol, 2008, 14(11):1657-1663.
[19]
Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG)[J]. Mol Endocrinol, 1997, 11(4):433-441.
[20]
Deugnier Y, David V, Brissot P, et al. Serum alpha-L-fucosidase: a new marker for the diagnosis of primary hepatic carcinoma?[J]. Hepatology, 1984, 4(5):889-892.
[1] 中国医师协会肝癌专业委员会. 肝细胞癌伴微血管侵犯诊断和治疗中国专家共识(2024版)[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 313-324.
[2] 丁丁, 杨云川, 马翔, 马中正, 霍俊一, 周磊. 术前C-反应蛋白-白蛋白-淋巴细胞比值在肝细胞癌预后中的价值评估[J/OL]. 中华普通外科学文献(电子版), 2024, 18(04): 261-265.
[3] 汤宏涛, 何坤. 中晚期肝细胞癌介入治疗的进展及前景[J/OL]. 中华普通外科学文献(电子版), 2024, 18(04): 305-308.
[4] 李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[5] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[6] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[7] 公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[8] 李一帆, 朱帝文, 任伟新, 鲍应军, 顾俊鹏, 张海潇, 曹耿飞, 阿斯哈尔·哈斯木, 纪卫政. 血GP73水平在原发性肝癌TACE疗效评价中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 825-830.
[9] 刘敏思, 李荣, 李媚. 基于GGT与Plt比值的模型在HBV相关肝细胞癌诊断中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 831-835.
[10] 焦振东, 惠鹏, 金上博. 三维可视化结合ICG显像技术在腹腔镜肝切除术治疗复发性肝癌中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 859-864.
[11] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[12] 袁雨涵, 杨盛力. 体液和组织蛋白质组学分析在肝癌早期分子诊断中的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 883-888.
[13] 吴警, 吐尔洪江·吐逊, 温浩. 肝切除术前肝功能评估新进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 889-893.
[14] 邓万玉, 陈富, 许磊波. 肝硬化与非肝硬化乙肝相关性肝癌患者术后无复发生存比较及其影响因素分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 670-674.
[15] 王向前, 李清峰, 陈磊, 丘文丹, 姚志成, 李熠, 吴荣焕. 姜黄素抑制肝细胞癌索拉非尼耐药作用及其调控机制[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 729-735.
阅读次数
全文


摘要