- Original article
- Open access
- Published:
Evaluation of serum endoglin as noninvasive marker in hepatocellular carcinoma
The Egyptian Journal of Internal Medicine volume 27, pages 15–20 (2015)
Abstract
Introduction
Hepatitis C viral (HCV) infection is a major risk factor for liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). A number of laboratory-based methods has been developed for the noninvasive diagnostic evaluation of HCC. Endoglin (CD105) is a homodimeric membrane glycoprotein expressed on endothelial cells that can bind to transforming growth factor-b1 and transforming growth factor-b3.
Aim of the study
The aim of this study was to evaluate the diagnostic value of endoglin and a-fetoprotein (AFP) in patients with chronic HCV infection with and without HCC.
Patients and methods
A total of 50 HCV patients were chosen and divided into two patients groups, group I (26 cirrhotic patients) and group II (24 HCC patients), and compared with group III (10 healthy volunteers) as controls. For all participants, thorough clinical examination, blood picture, liver function tests, HCV antibody, AFP, and serum endoglin were performed. Abdominal ultrasound, abdominal triphasic computed tomographic scan, and liver biopsy for those diagnosed HCC by triphasic computed tomography were performed.
Results
We found highly significant increase in serum endoglin in HCV patients with HCC (group III) compared with HCV patients with liver cirrhosis (group I) and controls (group III). There was significant positive correlation between serum endoglin and aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and AFP. In addition, there was significant negative correlation between serum endoglin and hemoglobin, albumin, and prothrombin concentration. The cutoff value for serum AFP for which HCC is suspected was greater than 2.17 ng/ml with sensitivity 98% and specificity 80%, whereas the cutoff value for serum endoglin was greater than 6.05 ng/ml with sensitivity 98% and specificity 90%.
Conclusion
Serum endoglin surpassed serum AFP due to the higher degree of diagnostic specificity, as well as sensitivity. Serum endoglin showed a better diagnostic performance and proved to be more reliable as a tumor marker for HCC. Serum endoglin may be used with serum AFP as complementary biomarker as noninvasive technique to aid diagnosis of HCC.
References
Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005; 5:558–567.
Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007; 13:2436–244.
Wasfi OAS, Sadek NA. Prevalence of hepatitis B surface antigen and hepatitis C virus antibodies among blood donors in Alexandria, Egypt. East Mediterr Health J 2011; 17:238–242.
Tabll A, Shoman S, Ghanem H, Nabil M, El Din NGB, El Awady MK. Assessment of human cytomegalovirus co-infection in Egyptian chronic HCV patients. Virol J 2011; 8:343.
Hanafi MI, Mohamed AM, Kassem MS, Shawki M. Needlestick injuries among health care workers of University of Alexandria Hospitals. East Mediterr Health J 2011; 17:26–35.
Ahmed AM, Hassan MS, Abd-Elsayed A, Hassan H, Hasanain AF, Helmy A. Insulin resistance, steatosis, and fibrosis in Egyptian patients with chronic Hepatitis C virus infection. Saudi J Gastroenterol 2011; 17:245–251.
Huang S, He X. The role of microRNAs in liver cancer progression. Br J Cancer 2011; 104:235–240.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365:1118–1127.
Sherman M, Klein A. AASLD single-topic research conference on hepatocellular carcinoma: conference proceedings. Hepatology 2004; 40:1465–1473.
Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?. Am J Gastroenterol 2006; 101:524–532.
Lopez-Novoa JM, Bernabeu C. The physiological role of endoglin in the cardiovascular system. Am J Physiol Heart Circ Physiol 2010; 299:H959–H974.
Nassiri F, Cusimano MD, Scheithauer BW, Rotondo F, Fazio A, Yousef GM. Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res 2011; 31:2283–2290.
Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, et al. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver. World J Gastroenterol 2005; 11:176–181.
Richard K, Sterling M, Wright EC, Morgan TR, Seeff LB, Hoefs JC, et al. Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C. Am J Gastroenterol 2009; 107:64–74.
Maynard SE, Moore Simas TAL, Bur L, Crawford MJ, Solitro MJ, et al. Soluble endoglin for the prediction of preeclampsia in a high risk cohort. Hypertens Pregnancy 2010; 29:330–341.
Miller FD, Abu-Raddad LJ. Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt. Proc Natl Acad Sci USA 2010; 107:14757–14762.
Wand J. Prevention of hepatocellular carcinoma. N Engl J Med 2004; 351:1567–1570.
European Association for the Study of the Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56:908–943.
Sterling L, Jeffers F, Gordon F, Venook AP, Reddy KR, Satomura S, et al. Utility of Lens culinaris agglutinin-reactive fraction of alpha feto protein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2012; 7:104–113.
Villanueva A, Minguez B, Forner A, Reig M, Llovet JM. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med 2010; 61:317–328.
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371:838–851.
Wedemeyer H, Hofmann WP, Lueth S, Malinski P, Thimme R, Tacke F, et al. ALT screening for chronic liver diseases: scrutinizing the evidence. Z Gastroenterol 2010; 489:46–55.
McHutchison JG, Manns MP, Longo DL. Definition and management of anemia in patients infected with hepatitis C virus. Liver Int 2006; 26:389–398.
Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006; 44:1039–1046.
MC Yu, KM Chan, CF Lee, YS Lee, FZ Eldeen, HS Chou, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence?. J Gastrointest Surg 2011; 15:1440–1449.
Preativatanyou K, Honsawek S, Chongsrisawat V, Vejchapipat P, Theamboonlers A, Poovorawan Y. Correlation of circulating endoglin with clinical outcome in biliary atresia. Eur J Pediatr Surg 2010; 20:237–241.
Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-b signaling in fibrosis. Growth Factors 2011; 29:196–202.
Dooley S, Dijke P. TGF-b in progression of liver disease. Cell Tissue Res 2012; 347:245–256.
Meurer SK, Tihaa L, Borkham-Kamphorst E, Weiskirchen R. Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibrogenic Smad signalling. Cell Signal 2011; 23:683–699.
Talaat M, El-Sayed N, Kandeel A, Azab MA, Afifi S, Youssef FG, et al. Sentinel surveillance for patients with acute hepatitis in Egypt, 2001–04. East Mediterr Health J. 2010; 16:134–140.
Esmat G, Hashem M, El-Raziky M, El-Akel W, El-Naghy S, El-Koofy N, et al. Risk factors for hepatitis C virus acquisition and predictors of persistence among Egyptian children. Liver Int 2011; 10:1478–3231.
Ezzat S, Abdel-Hamid M, Eissa SA. Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt. Int J Hyg Environ Health 2005; 208:329–339.
Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol 2006; 12:1175–1181.
Yagmur E, Rizk M, Stanzel S, Hellerbrand C, Lammert F, Trautwein C, et al. Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma. Eur J Gastroenterol Hepatol 2007; 9:755–761.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Mohamed, R.A., Maghraby, H.M., Abd El Salam, E.M. et al. Evaluation of serum endoglin as noninvasive marker in hepatocellular carcinoma. Egypt J Intern Med 27, 15–20 (2015). https://doi.org/10.4103/1110-7782.155832
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.4103/1110-7782.155832