Identification of Specific Biomarker Genes for Separating Intrahepatic Cholangiocarcinoma Type

  • Thitiluck Swangsri Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine,Mahidol University
Keywords: Intrahepatic Cholangiocarcinoma Biomarker genes

Abstract

Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. ICC is classified into 3 types: mass-forming (MF), periductal infiltrating (PI), and intraductal growth (IG). Among these, the PI and IG types are located in the bile duct, so that histopathologic diagnosis may be quite difficult. This study aims to identify the specific biomarkers for distinguish between PI and IG types. The top five up-regulated genes from PI (C19ORF33, UPK1B, CTHRC1, GREM1, KLK11) and IG type (CFTR, SLC5A1, MUC17, BDKRB2, CCL18) were examined in ICC samples (11 PI and 11 IG samples) using SYBR green-based real-time reverse transcription-PCR (qRT-PCR). Among these genes, the results showed that the CTHRC1 gene of the PI type identified with the highest up-regulation in PI (72.7%) and 27.3% in IG samples (P=0.034), whereas the CFTR gene of the IG type showed the highest up-regulation in 72.7% of IG and 9.1% of PI samples (P=0.001). Hence, the up-regulation of CTHRC1 and CFTR may serve as biomarkers for separating PI from IG types, respectively, and is also a potential diagnostic in ICC. (Thai Cancer J 2020;40:76-85)

 

Downloads

Download data is not yet available.

References

Khan SA,Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma.Lancet 2005;366:1303-14.

Ustundag Y, Bayraktar Y. Cholangiocarcinoma: a compactreview of the literature. World J Gastroenterol 2008;14:6458-66.

Mosconi S, Beretta GD, Labianca R, Zampino MG, Gatta G, Heinemann V. Cholangiocarcinoma. Crit Rev Oncol Hematol 2009;69:259-70.

Thamavit W, Pairojkul C, Tiwawech D, Shirai T, Ito N. Strong promoting effect of Opisthorchis viverrini infection on dimethyl nitrosamine-initiated hamster liver. Cancer Lett 1994;78:121-5.

Sripa B, Pairojkul C. Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastro enterol 2008;24:349-56.

Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin DM. Prevalence of Opisthorchis viverrini infection and incidence of Cholangio-carcinoma in Khon Kaen, Northeast Thailand. Trop Med Int Health 2004;9:588-94.

Rimola J, Forner A, Reig M, Vilana R, de Lope CR, Ayuso C, et al. Cholangiocarcinoma in irrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology 2009;50:791-8.

Hansel DE, Rahman A, Hidalgo M, Thuluvath PJ, Lillemoe KD, Shulic KR, et al. Identification of novel cellular targets in biliary tract cancers using global gene expression technology. Am J Pathol 2003; 163:217-29.

Jinawath N, Chamgramol V, Furukawa Y, Obama K, Tsunoda T, Sripa B, et al. Comparison of gene expression profiles between Opisthorchis viverrini and Non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma. Hepatology 2006;44:1025-38.

Obama K, Ura K, Li M, Katagiri T, Tsunoda T, Nomura A, et al. Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepatology 2005;41:1339-48.

Wan AG, Yoon SY, Oh Jh, Jeon YJ, Kim M, Kim JM, et al. Identification of intrahepatic cholangiocarcinoma related genes by comparison with normal liver sample using expressed sequence tags. Biochem Biophys Res Commun 2006;345:1022-32.

Subrungruang I, Thawornkuno C, Petmitr CP, Pairojkul C, Wongkham S, Petmitr S. gene expression profiling of intrahepatic Cholangiocarcinoma. Asian Pac J cancer Prev 2013;14:557-63.

Subrungruang I. Study of genetic profile in cholangiocarcinoma [Ph.D. (Tropical Medicine) Thesis in Tropical Nutrition and Food Science]. Bangkok: Faculty of Graduate Studies, Mahidol University; 2012.

Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001;33:1353-7.

Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol 2004;40:472-7.

Welzel TM, McGlynn KA, Hsing AW, O'Brien TR, Pfeiffer RM. Impact of classification of hilar cholangio-

carcinomas(Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst 2006;98:873-5.

Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014;60:1268-89.

Jiang N, Cui Y, Liu J, Zhu X, Wu H, Yang Z, et al.Multidimensional roles of collagen triple helix repeat containing 1 (CTHRC1) in malignant cancers. J Cancer 2016 ;7:2213-20.

Ke Z, He W, Lai Y, Guo X, Chen S, Li S, et al. Overexpression of collagen triple helix repeat containing 1CTHRC1) is associated with tumor aggressiveness and poor prognosis in human non-small cell lung cancer. Oncotarget 2014; 5: 9410-24.

Hou M, Cheng Z, Shen H, He S, Li Y, Pan Y, et al. High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis. Oncotarget 2015;6:35813-29.

Kim HC, Kim YS, Oh HW, Kim K, Oh SS, Kim JT, et al. Collagen triple helix repeat containing1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget 2014;5:519-29.

Chen YL, Wang TH, Hsu HC, Yuan RH, Jeng YM. Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis. PLoS one 2013;8:1-10.

Kim JH, Baek TH, Yim HS, Kim KH, Jeong SH, Kang HB, et al. Collagen triple helix repeat containing-1 (CTHRC1) expressionin invasive ductal carcinoma of the breast: the impact on prognosis and correlation to clinic opathologic features. Pathol Oncol Res 2013;19:731-7.

Tang L, Dai DL, Su M, Martinka M, Li G, Zhou Y. Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers. Clin Cancer Res 2006;12:3716-22.

Cohn JA, Strong TV, Picciotto MR, Nairn AC, Collins FS, Fitz JG. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology 1993;105:1857-64.

Warren N, Holmes JA, al-Jader L, West RR, Lewis DC, Padua RA. Frequency of carriers of cystic fibrosis gene among patients with myeloid malignancy and melanoma. BMJ 1991;302:760-1.

Padua RA, Warren N, Grimshaw D, SmithM, Lewis C, Whittaker J, et al. The cystic fibrosis delta F508 gene mutation and cancer. Hum Mutat 1997;10:45-8.

Li J, Zhang JT, Jiang X, Shi X, Shen J, Feng F, et al. The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer. Int J Oncol 2015;46:2107-15.

Zhang JT, Jiang XH, Xie C, Cheng H, Da Dong J, Wang Y, et al. Downregulation of CFTR promotes epithelial-to-mesenchymaltransition and is associated with poor prognosis of breast cancer. Biochim Biophys Acta 2013; 1833:2961-9.

Peng X, Wu Z, Yu L, Li J, Xu W, Chan HC, et al. Overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) is associated with human cervical cancer malignancy, progression and prognosis. Gynecol Oncol 2012;125:470-6.

Pall H, Zielenski J, Jonas MM, DaSilva DA, Potvin KM, Yuan XW, et al. Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function. J Pediatr 2007;151:255-9.

Shoda J, Kano M, Asano T, Irimura T, Ueda T,Iwasaki R, et al. Secretory low-molecular weight Phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: Factors of chronic proliferative cholangitis. Hepatology 1999;29:1025-36.

Kim HJ, Lee SK, Kim MH, Son JM, Lee SS, Park JS, et al. Cystic fibrosis transmembrane conductance regulators (CFTR) in biliary epithelium of patients with hepatolithiasis. Dig Dis Sci 2002;47:1758-65.

Mori T, Sugiyama M, Atomi Y. Gallstone disease: Management of intrahepatic stones. Best Pract Res Clin Gastroenterol 2006;20:1117-37.

Ntoulia M, Kaklamanis L, Valavanis C, Kafousi M, Stathopoulos E, Arapantoni P, et al. HER-2 DNA quantification of paraffin-embedded breast carcinomas with Light Cycler real-time PCR in comparison to immunohistochemistry and chromogenic in situ hybridization. Clin Biochem 2006; 39:942-6.

Gheni N. Westenberg D. Quantitative real-time PCR assay with immunohistochemicalevaluation of HER2/ neu oncogene in breast cancer patients and its correlation with clinicopathological findings. Indian J Pathol Microbiol 2020;63:S123-8.

Nistor A, Watson PH, Pettigrew N, Tabiti K, Dawson A, Myal Y. Real-time PCR complements immunohistochemistry in the determination of HER-2/ neu status in breast cancer. BMC Clin Pathol 2006;6:1-8.

Published
2020-07-10
Section
Original Articles