Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

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  • 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
  • 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

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.

OriginalsprogEngelsk
TidsskriftCancer Cell
Vol/bind32
Udgave nummer1
Sider (fra-til)57-70.e3
ISSN1535-6108
DOI
StatusUdgivet - 10 jul. 2017

ID: 182354924