Identification of Hepatoma-derived Growth Factor As a Potential Prognostic and Diagnostic Marker for Extrahepatic Cholangiocarcinoma

Overview

Journal World J Surg

Publisher Wiley

Specialty General Surgery

Date 2013 Jun 25

PMID 23793608

Citations 4

Authors

Yuxia Han

Wenxia Zhang

Yanfeng Liu

Affiliations

Soon will be listed here.

Abstract

Background: Hepatoma-derived growth factor (HDGF) has been reported to play a pivotal role in the development and progression of several tumors. The aim of the present study was to analyze whether HDGF is a potential prognostic and diagnostic marker for extrahepatic cholangiocarcinoma (EHCC).

Methods: The immunostaining of HDGF was analyzed by immunohistochemistry for 65 pathologically confirmed EHCC, and its correlation with clinicopathologic factors and prognosis was investigated. Meanwhile, to evaluate the diagnostic value of HDGF, an enzyme-linked immunosorbent assay (ELISA) was performed to measure HDGF levels in the serum samples of 83 EHCC patients and 51 healthy controls.

Results: Positive expression of HDGF was detected in 30 (46.2 %) patients with EHCC and correlated with poor tumor differentiation (P = 0.024). Univariate analysis showed that the positive HDGF expression group had a significantly poorer survival rate than the negative HDGF expression group did (P < 0.001). Multivariate analysis demonstrated that HDGF expression and N stage were independent prognostic factors. The mean serum HDGF level in EHCC patients was 2.39-fold higher than that in healthy controls (P = 0.002). The optimal cut-off value for HDGF was 122.15 pg/mL, providing a sensitivity of 66.27 % and a specificity of 88.24 %. The area under the curve (AUC) of HDGF was 0.807 (95 % confidence interval 0.730-0.870), demonstrating that HDGF was a potential biomarker for EHCC.

Conclusions: HDGF was a valuable independent prognostic factor after curative resection in EHCC, and it provided an important basis for screening/treating high-risk patients. Meanwhile, our study indicated that serum HDGF levels can be used as a noninvasive and potential diagnostic marker for EHCC.

Citing Articles

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies.

Enomoto H, Nakamura H, Nishikawa H, Nishiguchi S, Iijima H Int J Mol Sci. 2020; 21(12).

PMID: 32545762 PMC: 7352308. DOI: 10.3390/ijms21124216.

Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy.

Keane M, Shah A, Pereira S, Joshi D F1000Res. 2017; 6:1643.

PMID: 28944047 PMC: 5585877. DOI: 10.12688/f1000research.11371.1.

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?.

Park H, Kim K, Paik J, Chie E, Kim S, Jang J Clin Transl Oncol. 2015; 18(6):625-31.

PMID: 26459257 DOI: 10.1007/s12094-015-1409-5.

A new clinically based staging system for perihilar cholangiocarcinoma.

Chaiteerakij R, Harmsen W, Marrero C, Aboelsoud M, Ndzengue A, Kaiya J Am J Gastroenterol. 2014; 109(12):1881-90.

PMID: 25384902 PMC: 4341961. DOI: 10.1038/ajg.2014.327.

References

Akdogan M, Sasmaz N, Kayhan B, Biyikoglu I, Disibeyaz S, Sahin B . Extraordinarily elevated CA19-9 in benign conditions: a case report and review of the literature. Tumori. 2002; 87(5):337-9. DOI: 10.1177/030089160108700513. View

Uyama H, Tomita Y, Nakamura H, Nakamori S, Zhang B, Hoshida Y . Hepatoma-derived growth factor is a novel prognostic factor for patients with pancreatic cancer. Clin Cancer Res. 2006; 12(20 Pt 1):6043-8. DOI: 10.1158/1078-0432.CCR-06-1064. View

Weidner N, Semple J, Welch W, Folkman J . Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991; 324(1):1-8. DOI: 10.1056/NEJM199101033240101. View

Yu Y, Shen H, Yu H, Zhong F, Zhang Y, Zhang C . Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis. Mol Biosyst. 2011; 7(6):1908-16. DOI: 10.1039/c0mb00265h. View

Hicklin D, Ellis L . Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2004; 23(5):1011-27. DOI: 10.1200/JCO.2005.06.081. View

Mobius C, Demuth C, Aigner T, Wiedmann M, Wittekind C, Mossner J . Evaluation of VEGF A expression and microvascular density as prognostic factors in extrahepatic cholangiocarcinoma. Eur J Surg Oncol. 2007; 33(8):1025-9. DOI: 10.1016/j.ejso.2007.02.020. View

Yoshida K, Nakamura H, Okuda Y, Enomoto H, Kishima Y, Uyama H . Expression of hepatoma-derived growth factor in hepatocarcinogenesis. J Gastroenterol Hepatol. 2003; 18(11):1293-301. DOI: 10.1046/j.1440-1746.2003.03191.x. View

Lee K, Choi E, Kim M, Lee S, Jang B, Kim T . Hepatoma-derived growth factor regulates the bad-mediated apoptotic pathway and induction of vascular endothelial growth factor in stomach cancer cells. Oncol Res. 2011; 19(2):67-76. DOI: 10.3727/096504010x12864748215043. View

Okuda Y, Nakamura H, Yoshida K, Enomoto H, Uyama H, Hirotani T . Hepatoma-derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor. Cancer Sci. 2003; 94(12):1034-41. PMC: 11160104. DOI: 10.1111/j.1349-7006.2003.tb01397.x. View

10.

Patel T . Cholangiocarcinoma. Nat Clin Pract Gastroenterol Hepatol. 2006; 3(1):33-42. DOI: 10.1038/ncpgasthep0389. View

11.

Ren H, Tang X, Lee J, Feng L, Everett A, Hong W . Expression of hepatoma-derived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer. J Clin Oncol. 2004; 22(16):3230-7. DOI: 10.1200/JCO.2004.02.080. View

12.

Hu T, Huang C, Liu L, Lin P, Liu S, Chang H . Expression of hepatoma-derived growth factor in hepatocellular carcinoma. Cancer. 2003; 98(7):1444-56. DOI: 10.1002/cncr.11653. View

13.

Yamamoto S, Tomita Y, Hoshida Y, Takiguchi S, Fujiwara Y, Yasuda T . Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma. Clin Cancer Res. 2006; 12(1):117-22. DOI: 10.1158/1078-0432.CCR-05-1347. View

14.

Zhang A, Long W, Guo Z, Liu G, Hu Z, Huang Y . Development and clinical evaluation of a multi-purpose mAb and a sandwich ELISA test for hepatoma-derived growth factor in lung cancer patients. J Immunol Methods. 2010; 355(1-2):61-7. DOI: 10.1016/j.jim.2010.02.011. View

15.

Meng J, Xie W, Cao L, Hu C, Zhe Z . shRNA targeting HDGF suppressed cell growth and invasion of squamous cell lung cancer. Acta Biochim Biophys Sin (Shanghai). 2010; 42(1):52-7. DOI: 10.1093/abbs/gmp102. View

16.

Hu T, Lin J, Chen H, Liu L, Chuah S, Tai M . The expression and prognostic role of hepatoma-derived growth factor in colorectal stromal tumors. Dis Colon Rectum. 2009; 52(2):319-26. DOI: 10.1007/DCR.0b013e31819d1666. View

17.

Mao J, Xu Z, Fang Y, Wang H, Xu J, Ye J . Hepatoma-derived growth factor involved in the carcinogenesis of gastric epithelial cells through promotion of cell proliferation by Erk1/2 activation. Cancer Sci. 2008; 99(11):2120-7. PMC: 11159754. DOI: 10.1111/j.1349-7006.2008.00928.x. View

18.

Kishima Y, Yamamoto H, Izumoto Y, Yoshida K, Enomoto H, Yamamoto M . Hepatoma-derived growth factor stimulates cell growth after translocation to the nucleus by nuclear localization signals. J Biol Chem. 2001; 277(12):10315-22. DOI: 10.1074/jbc.M111122200. View

19.

Nakamura H, Kambe H, Egawa T, Kimura Y, Ito H, Hayashi E . Partial purification and characterization of human hepatoma-derived growth factor. Clin Chim Acta. 1989; 183(3):273-84. DOI: 10.1016/0009-8981(89)90361-6. View

20.

Patel A, Harnois D, Klee G, Larusso N, Gores G . The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol. 2000; 95(1):204-7. DOI: 10.1111/j.1572-0241.2000.01685.x. View