본문 바로가기
KERD
논문KCI 등재

Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

초록

Background/Aims: α-Fetoprotein (AFP) is the biomarkermost widely used to detect hepatocellular carcinoma (HCC),despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3)and osteopontin (OPN) are secreted glycoproteins that are reportedlyassociated with tumorigenesis and metastasis. Thisstudy was conducted to evaluate the clinical utility of usingplasma GPC3 and OPN as diagnostic biomarkers for HCC. Methods: We measured the plasma levels of GPC3 and OPNin 120 HCC and 40 chronic liver disease (CLD) patients viaan enzyme-linked immunosorbent assay. The diagnostic accuracyof each tumor marker was evaluated using receiveroperating characteristic (ROC) curve analysis. Results: TheGPC3 levels in the HCC patients (75.8 ng/mL) were significantlyhigher (p=0.020) than the levels in patients withCLD (66.4 ng/mL). The area under the ROC curve (AUROC)values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patientswith low serum AFP and PIVKA II levels, the AUROC of GPC3remained relatively high (0.66), and GPC3 showed a highsensitivity (62.1%) for detecting small HCC tumors. Conclusions:The plasma levels of GPC3 and OPN demonstratedlow diagnostic accuracy for HCC. However, GPC3 may havea complementary role in diagnosing HCC in patients withnondiagnostic levels of conventional tumor markers and withsmall-sized tumors.

Abstract

Background/Aims: α-Fetoprotein (AFP) is the biomarkermost widely used to detect hepatocellular carcinoma (HCC),despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3)and osteopontin (OPN) are secreted glycoproteins that are reportedlyassociated with tumorigenesis and metastasis. Thisstudy was conducted to evaluate the clinical utility of usingplasma GPC3 and OPN as diagnostic biomarkers for HCC. Methods: We measured the plasma levels of GPC3 and OPNin 120 HCC and 40 chronic liver disease (CLD) patients viaan enzyme-linked immunosorbent assay. The diagnostic accuracyof each tumor marker was evaluated using receiveroperating characteristic (ROC) curve analysis. Results: TheGPC3 levels in the HCC patients (75.8 ng/mL) were significantlyhigher (p=0.020) than the levels in patients withCLD (66.4 ng/mL). The area under the ROC curve (AUROC)values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patientswith low serum AFP and PIVKA II levels, the AUROC of GPC3remained relatively high (0.66), and GPC3 showed a highsensitivity (62.1%) for detecting small HCC tumors. Conclusions:The plasma levels of GPC3 and OPN demonstratedlow diagnostic accuracy for HCC. However, GPC3 may havea complementary role in diagnosing HCC in patients withnondiagnostic levels of conventional tumor markers and withsmall-sized tumors.

참고문헌 (36)

  1. Venook AP, "The incidence and epidemiology of hepatocellular carcinoma : a global and regional perspective", Oncologist, 15(Suppl 4), pp.5~13 (2010)
  2. El-Serag HB, "Hepatocellular carcinoma", N Engl J Med, 365, pp.1118~1127 (2011)
  3. Stravitz RT, "Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome", Am J Med, 121, pp.119~126 (2008)
  4. Bruix J, "Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)
  5. McMahon BJ, "Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study", Hepatology, 32(4 Pt 1), pp.842~846 (2000)
  6. Sherman M, "Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population", Hepatology, 22, pp.432~438 (1995)
  7. Kasahara A, "Clinical evaluation of plasma des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes", Dig Dis Sci, 38, pp.2170~2176 (1993)
  8. Ikoma J, "Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gammacarboxy prothrombin: a prospective study", Hepatogastroenterology, 49, pp.235~238 (2002)
  9. Lok AS, "Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma", Gastroenterology, 138, pp.493~502 (2010)
  10. Capurro M, "Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma", Gastroenterology, 125, pp.89~97 (2003)
  11. Nakatsura T, "Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker", Biochem Biophys Res Commun, 306, pp.16~25 (2003)
  12. Anborgh PH, "Role of the metastasis-promoting protein osteopontin in the tumour microenvironment", J Cell Mol Med, 14, pp.2037~2044 (2010)
  13. El-Tanani MK, "Role of osteopontin in cellular signaling and metastatic phenotype", Front Biosci, 13, pp.4276~4284 (2008)
  14. Johnston NI, "Osteopontin as a target for cancer therapy", Front Biosci, 13, pp.4361~4372 (2008)
  15. Pan HW, "Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma", Cancer, 98, pp.119~127 (2003)
  16. Gotoh M, "Overexpression of osteopontin in hepatocellular carcinoma", Pathol Int, 52, pp.19~24 (2002)
  17. Bruix J, "Management of hepatocellular carcinoma", Hepatology, 42, pp.1208~1236 (2005)
  18. Vauthey JN, "Simplified staging for hepatocellular carcinoma", J Clin Oncol, 20, pp.1527~1536 (2002)
  19. Forner A, "Current strategy for staging and treatment: the BCLC update and future prospects", Semin Liver Dis, 30, pp.61~74 (2010)
  20. Filmus J, "Glypicans: proteoglycans with a surprise", J Clin Invest, 108, pp.497~501 (2001)
  21. Lin H, "Frequent silencing of the GPC3 gene in ovarian cancer cell lines", Cancer Res, 59, pp.807~810 (1999)
  22. Murthy SS, "Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma", Oncogene, 19, pp.410~416 (2000)
  23. Hsu HC, "Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma:biological significance and temporospatial distribution", Cancer Res, 57, pp.5179~5184 (1997)
  24. Liu H, "Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma", World J Gastroenterol, 16, pp.4410~4415 (2010)
  25. Tangkijvanich P, "Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers", J Gastroenterol Hepatol, 25, pp.129~137 (2010)
  26. Qiao SS, "Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma", Hepatogastroenterology, 58, pp.1718~1724 (2011)
  27. Singal A, "Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis", Aliment Pharmacol Ther, 30, pp.37~47 (2009)
  28. Trevisani F, "Serum alphafetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status", J Hepatol, 34, pp.570~575 (2001)
  29. Wai PY, "The role of Osteopontin in tumor metastasis", J Surg Res, 121, pp.228~241 (2004)
  30. Zhang CH, "Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis", Int J Cancer, 130, pp.2685~2692 (2012)
  31. Kim J, "Elevated plasma osteopontin levels in patients with hepatocellular carcinoma", Am J Gastroenterol, 101, pp.2051~2059 (2006)
  32. Zhang H, "The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma", J Cancer Res Clin Oncol, 132, pp.709~717 (2006)
  33. Shang S, "Identification of osteopontin as a novel marker for early hepatocellular carcinoma", Hepatology, 55, pp.483~490 (2012)
  34. Lorena D, "Osteopontin expression in normal and fibrotic liver altered liver healing in osteopontindeficient mice", J Hepatol, 44, pp.383~390 (2006)
  35. Syn WK, "Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis", Hepatology, 53, pp.106~115 (2011)
  36. Urtasun R, "Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin α(V)β(3) engagement and PI3K", pAkt, Hepatology, pp.2012, 55[DOI]

관련 논문AI추천

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis김진욱, 장은선, 전예주, 정숙향, 최윤숙대한간학회 · Clinical and Molecular Hepatology2016 · 제22권 제3호Feasibility of α-fetoprotein as a diagnostic tool for hepatocellular carcinoma in Korea강현, 배시현, 이준성, 이현웅, Dae Geon Ahn, Hyung Joon Kim, Joon Hyoek Lee, Yong Han Paik대한내과학회 · The Korean Journal of Internal Medicine2016 · 제31권 제1호간세포암의 진단과 치료에서 종양표지자의 역할장영, 장재영대한내과학회 · 대한내과학회지2020 · 제95권 제1호Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma김도영, 김범경, 김승업, 김현숙, 김혜미, 박전한, 박준용, 백신화, 안상훈, 이재면, 이종두, 이현규, 최성훈, 한광협연세대학교의과대학 · Yonsei Medical Journal2015 · 제56권 제5호Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary MalignanciesEugene Kim, Ju Dong Yang, Lewis R. Roberts, Rachel A. Pedersen, Surakit Pungpapong, W. Ray Kim거트앤리버 소화기연관학회협의회 · Gut and Liver2010 · 제4권 제4호Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region김도영, Bao Nguyen Toan, Chee-Kiat Tan, Henry Lik Yuen Chan, Irsan Hasan, Lyana Setiawan, Ming-Lung Yu, Namiki Izumi, Nguyen Nguyen Huyen, Pierce Kah-Hoe Chow, Rosmawati Mohamed, Stephen Lam Chan, Tawesak Tanwandee, Teng-Yu Lee, Thi Thanh Nguyen Hai, Tian Yang, Woochang Lee대한간학회 · Clinical and Molecular Hepatology2023 · 제29권 제2호

이 간행물의 다른 논문 (15건)