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Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays

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Background/Aims: The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed. Methods: To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (AffymetrixU133A) were used. Overexpressed genes were checked for their potential use as new markers for discrimination and their expression values were validated by reverse transcription polymerase chain reaction and immunohistochemistry analyses. Results: 695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p<0.05, fold change >2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and nonmalignant liver tissues was established. A panel of 12 genes (e.g., HSP90, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers. Conclusions: A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.

Abstract

Background/Aims: The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed. Methods: To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (AffymetrixU133A) were used. Overexpressed genes were checked for their potential use as new markers for discrimination and their expression values were validated by reverse transcription polymerase chain reaction and immunohistochemistry analyses. Results: 695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p<0.05, fold change >2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and nonmalignant liver tissues was established. A panel of 12 genes (e.g., HSP90, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers. Conclusions: A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.

참고문헌 (45)

  1. El-Serag HB, "Hepatocellular carcinoma: an epidemiologic view", J Clin Gastroenterol, 35(5 Suppl 2), pp.S72~S78 (2002)[DOI]
  2. Davila JA, "Cholangiocarcinoma: the other liver cancer on the rise", Am J Gastroenterol, 97, pp.3199~3200 (2002)
  3. McGlynn KA, "International trends and patterns of primary liver cancer", Int J Cancer, 94, pp.290~296 (2001)[DOI]
  4. El-Serag HB, "Hepatocellular carcinoma: epidemiology and molecular carcinogenesis", Gastroenterology, 132, pp.2557~2576 (2007)[DOI]
  5. Yao FY, "A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy", Liver Transpl, 9, pp.684~692 (2003)[DOI]
  6. Llovet JM, "Sorafenib in advanced hepatocellular carcinoma", N Engl J Med, 359, pp.378~390 (2008)[DOI]
  7. Valle JW, "Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study - The UK ABC-01 Study", Br J Cancer, 101, pp.621~627 (2009)[DOI]
  8. Bruix J, "Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)[DOI]
  9. European Association for the Study of the Liver, "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma", J Hepatol, 56, pp.908~943 (2012)[DOI]
  10. Kim SA, "Intrahepatic mass-forming cholangiocarcinomas: enhancement patterns at multiphasic CT, with special emphasis on arterial enhancement pattern--correlation with clinicopathologic findings", Radiology, 260, pp.148~157 (2011)[DOI]
  11. Kang Y, "Intrahepatic massforming cholangiocarcinoma: enhancement patterns on gadoxetic acid-enhanced MR images", Radiology, 264, pp.751~760 (2012)[DOI]
  12. Nanashima A, "Intrahepatic cholangiocarcinoma: relationship between tumor imaging enhancement by measuring attenuation and clinicopathologic characteristics", Abdom Imaging, 38, pp.785~792 (2013)[DOI]
  13. Radwan NA, "The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1", Diagn Pathol, 7, pp.149~ (2012)[DOI]
  14. Lamps LW, "The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review", Adv Anat Pathol, 10, pp.39~43 (2003)[DOI]
  15. Kakar S, "Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms", Arch Pathol Lab Med, 131, pp.1648~1654 (2007)
  16. Chu PG, "Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alphafetoprotein", Am J Surg Pathol, 26, pp.978~988 (2002)[DOI]
  17. Kakar S, "Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumors and its correlation with albumin in situ hybridization in hepatocellular carcinoma", Am J Clin Pathol, 119, pp.361~366 (2003)[DOI]
  18. Minervini MI, "Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors", Mod Pathol, 10, pp.686~692 (1997)
  19. Lok AS, "Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma", Gastroenterology, 138, pp.493~502 (2010)[DOI]
  20. Marrelli D, "CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions", Am J Surg, 198, pp.333~339 (2009)[DOI]
  21. Man XB, "Upregulation of glypican-3 expression in hepatocellular carcinoma but downregulation in cholangiocarcinoma indicates its differential diagnosis value in primary liver cancers", Liver Int, 25, pp.962~966 (2005)[DOI]
  22. Wang L, "Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset", Tumour Biol, 34, pp.1679~1684 (2013)[DOI]
  23. Heringlake S, "Identification and expression analysis of the aldoketoreductase1-B10 gene in primary malignant liver tumours", J Hepatol, 52, pp.220~227 (2010)[DOI]
  24. Hass HG, "Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: detection by oligonucleotide microarray and real-time PCR analysis", World J Gastroenterol, 14, pp.2501~2510 (2008)[DOI]
  25. Rajeevan MS, "Validation of array-based gene expression profiles by real-time (kinetic) RTPCR", J Mol Diagn, 3, pp.26~31 (2001)[DOI]
  26. Ganjei P, "Histologic markers in primary and metastatic tumors of the liver", Cancer, 62, pp.1994~1998 (1988)[DOI]
  27. Fujiwara M, "Arginase-1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies", Cancer Cytopathol, 120, pp.230~237 (2012)[DOI]
  28. Rullier A, "Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis", Am J Surg Pathol, 24, pp.870~876 (2000)[DOI]
  29. Sugiki T, "Specific characteristics of scirrhous hepatocellular carcinoma", Hepatogastroenterology, 56, pp.1086~1089 (2009)
  30. Gambarin-Gelwan M, "Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation", Am J Gastroenterol, 95, pp.1535~1538 (2000)[DOI]
  31. Hass HG, "Diagnostic and prognostic aspects of hepatocellular carcinoma: a retrospective analysis in 145 patients", J Gastroenterol Hepatol Res, 6, pp.2358~2364 (2017)[DOI]
  32. Kokudo N, "Evidence-based clinical practice guidelines for hepatocellular carcinoma in Japan: the J-HCC guidelines", J Gastroenterol, 44(Suppl 19), pp.119~121 (2009)[DOI]
  33. Durnez A, "The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma: a possible progenitor cell origin", Histopathology, 49, pp.138~151 (2006)[DOI]
  34. Uenishi T, "Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence", Cancer Sci, 94, pp.851~857 (2003)[DOI]
  35. Park SY, "Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary", Hum Pathol, 33, pp.1078~1085 (2002)[DOI]
  36. Ahopelto K, "Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer", Cancer Biol Ther, 17, pp.163~168 (2016)[DOI]
  37. Tan GS, "Novel proteomic biomarker panel for prediction of aggressive metastatic hepatocellular carcinoma relapse in surgically resectable patients", J Proteome Res, 13, pp.4833~4846 (2014)[DOI]
  38. Corona G, "Differential proteomic analysis of hepatocellular carcinoma", Int J Oncol, 36, pp.93~99 (2010)
  39. Cheng W, "Role of the novel HSP90 inhibitor AUY922 in hepatocellular carcinoma: potential for therapy", Mol Med Rep, 12, pp.2451~2456 (2015)[DOI]
  40. Kobayashi H, "A Kunitz-type protease inhibitor, bikunin, inhibits ovarian cancer cell invasion by blocking the calcium-dependent transforming growth factor-beta 1 signaling cascade", J Biol Chem, 278, pp.7790~7799 (2003)[DOI]
  41. Bullard RS, "Functional analysis of the host defense peptide human beta defensin-1: new insight into its potential role in cancer", Mol Immunol, 45, pp.839~848 (2008)[DOI]
  42. Arimura Y, "Elevated serum betadefensins concentrations in patients with lung cancer", Anticancer Res, 24, pp.4051~4057 (2004)
  43. Sirnes S, "Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome", Int J Cancer, 131, pp.570~581 (2012)[DOI]
  44. Elzarrad MK, "Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium", BMC Med, 6, pp.20~ (2008)[DOI]
  45. Xue TC, "Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis", Tumour Biol, 36, pp.5891~5899 (2015)[DOI]

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