Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Jittiporn Chaisaingmongkol; Anuradha Budhu; Hien Dang; Siritida Rabibhadana; Benjarath Pupacdi; So Mee Kwon; Marshonna Forgues; Yotsawat Pomyen; Vajarabhongsa Bhudhisawasdi; Nirush Lertprasertsuke; Anon Chotirosniramit; Chawalit Pairojkul; Chirayu U Auewarakul; Thaniya Sricharunrat; Kannika Phornphutkul; Suleeporn Sangrajrang; Maggie Cam; Ping He; Stephen M Hewitt; Kris Ylaya; Xiaolin Wu; Jesper B Andersen; Snorri S Thorgeirsson; Joshua J Waterfall; Yuelin J Zhu; Jennifer Walling; Holly S Stevenson; Daniel Edelman; Paul S Meltzer; Christopher A Loffredo; Natsuko Hama; Tatsuhiro Shibata; Robert H Wiltrout; Curtis C Harris; Chulabhorn Mahidol; Mathuros Ruchirawat; Xin W Wang; TIGER-LC Consortium

doi:10.1016/j.ccell.2017.05.009

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Cancer Cell. 2017 Jul 10;32(1):57-70.e3. doi: 10.1016/j.ccell.2017.05.009. Epub 2017 Jun 22.

Authors

Jittiporn Chaisaingmongkol¹, Anuradha Budhu², Hien Dang², Siritida Rabibhadana³, Benjarath Pupacdi³, So Mee Kwon², Marshonna Forgues², Yotsawat Pomyen⁴, Vajarabhongsa Bhudhisawasdi⁵, Nirush Lertprasertsuke⁶, Anon Chotirosniramit⁶, Chawalit Pairojkul⁵, Chirayu U Auewarakul⁷, Thaniya Sricharunrat⁸, Kannika Phornphutkul⁹, Suleeporn Sangrajrang¹⁰, Maggie Cam¹¹, Ping He¹², Stephen M Hewitt¹³, Kris Ylaya¹³, Xiaolin Wu¹⁴, Jesper B Andersen¹⁵, Snorri S Thorgeirsson², Joshua J Waterfall¹⁶, Yuelin J Zhu¹⁶, Jennifer Walling¹⁶, Holly S Stevenson¹⁶, Daniel Edelman¹⁶, Paul S Meltzer¹⁶, Christopher A Loffredo¹⁷, Natsuko Hama¹⁸, Tatsuhiro Shibata¹⁹, Robert H Wiltrout²⁰, Curtis C Harris², Chulabhorn Mahidol²¹, Mathuros Ruchirawat²², Xin W Wang²³; TIGER-LC Consortium

Affiliations

¹ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok 10400, Thailand.
² Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
³ Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand.
⁴ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand.
⁵ Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
⁶ Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
⁷ HRH Princess Chulabhorn College of Medical Science, Bangkok 10210, Thailand.
⁸ Chulabhorn Hospital, Bangkok 10210, Thailand.
⁹ Rajavej Hospital, Chiang Mai 50000, Thailand.
¹⁰ National Cancer Institute, Bangkok 10400, Thailand.
¹¹ Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹² FDA, Silver Spring, MD 20993, USA.
¹³ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁴ Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
¹⁵ Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
¹⁶ Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁷ Georgetown University Medical Center, Washington, DC 20057, USA.
¹⁸ Division of Cancer Genomics, National Cancer Center Research Institute, The University of Tokyo, Tokyo 104-0045, Japan.
¹⁹ Division of Cancer Genomics, National Cancer Center Research Institute, The University of Tokyo, Tokyo 104-0045, Japan; Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 104-0045, Japan.
²⁰ Cancer Inflammation Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
²¹ Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; HRH Princess Chulabhorn College of Medical Science, Bangkok 10210, Thailand. Electronic address: pc@cri.or.th.
²² Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok 10400, Thailand. Electronic address: mathuros@cri.or.th.
²³ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: xw3u@nih.gov.

Abstract

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism. These molecular subtypes are found in 582 Asian, but less so in 265 Caucasian patients. Thus, Asian ICC and HCC, while clinically treated as separate entities, share common molecular subtypes with similar actionable drivers to improve precision therapy.

Keywords: TIGER-LC; cancer driver; cancer genomics; hepatocellular carcinoma; integrated genomics; intrahepatic cholangiocarcinoma; liver cancer; metabolomics; molecular subtypes; transcriptomics.

Published by Elsevier Inc.

MeSH terms

Asian People / genetics*
Carcinoma, Hepatocellular / diagnosis
Carcinoma, Hepatocellular / genetics*
Cholangiocarcinoma / diagnosis
Cholangiocarcinoma / genetics*
Cluster Analysis
Humans
Kaplan-Meier Estimate
Liver Neoplasms / diagnosis
Liver Neoplasms / genetics*
Prognosis
Transcriptome

Abstract

MeSH terms

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