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

doi:10.1016/j.ccell.2017.05.009

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 YlayaXiaolin 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

128 Citations (Scopus)

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. Chaisaingmongkol et al. identify common molecular subtypes linked to similar prognosis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma, clinically different malignancies, among Thai patients. These molecular subtypes are also found in other Asian patients, but rarely in Caucasian patients.

Original language	English
Journal	Cancer Cell
Volume	32
Issue number	1
Pages (from-to)	57-70.e3
ISSN	1535-6108
DOIs	https://doi.org/10.1016/j.ccell.2017.05.009
Publication status	Published - 10 Jul 2017

Keywords

Asian Continental Ancestry Group
Carcinoma, Hepatocellular
Cholangiocarcinoma
Cluster Analysis
Humans
Kaplan-Meier Estimate
Liver Neoplasms
Prognosis
Transcriptome
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2017.05.009

http://www.cell.com/article/S1535610817302052/pdf

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Chaisaingmongkol, J., Budhu, A., Dang, H., Rabibhadana, S., Pupacdi, B., Kwon, S. M., Forgues, M., Pomyen, Y., Bhudhisawasdi, V., Lertprasertsuke, N., Chotirosniramit, A., Pairojkul, C., Auewarakul, C. U., Sricharunrat, T., Phornphutkul, K., Sangrajrang, S., Cam, M., He, P., Hewitt, S. M., ... Wang, X. W. (2017). Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma. Cancer Cell, 32(1), 57-70.e3. https://doi.org/10.1016/j.ccell.2017.05.009

Chaisaingmongkol, J, Budhu, A, Dang, H, Rabibhadana, S, Pupacdi, B, Kwon, SM, Forgues, M, Pomyen, Y, Bhudhisawasdi, V, Lertprasertsuke, N, Chotirosniramit, A, Pairojkul, C, Auewarakul, CU, Sricharunrat, T, Phornphutkul, K, Sangrajrang, S, Cam, M, He, P, Hewitt, SM, Ylaya, K, Wu, X, Andersen, JB, Thorgeirsson, SS, Waterfall, JJ, Zhu, YJ, Walling, J, Stevenson, HS, Edelman, D, Meltzer, PS, Loffredo, CA, Hama, N, Shibata, T, Wiltrout, RH, Harris, CC, Mahidol, C, Ruchirawat, M & Wang, XW 2017, 'Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma', Cancer Cell, vol. 32, no. 1, pp. 57-70.e3. https://doi.org/10.1016/j.ccell.2017.05.009

@article{4dbc9e5a7d5147d1a790fdfe2b109ed7,

title = "Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma",

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. Chaisaingmongkol et al. identify common molecular subtypes linked to similar prognosis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma, clinically different malignancies, among Thai patients. These molecular subtypes are also found in other Asian patients, but rarely in Caucasian patients.",

keywords = "Asian Continental Ancestry Group, Carcinoma, Hepatocellular, Cholangiocarcinoma, Cluster Analysis, Humans, Kaplan-Meier Estimate, Liver Neoplasms, Prognosis, Transcriptome, Journal Article",

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

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T1 - Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

AU - Chaisaingmongkol, Jittiporn

AU - Budhu, Anuradha

AU - Dang, Hien

AU - Rabibhadana, Siritida

AU - Pupacdi, Benjarath

AU - Kwon, So Mee

AU - Forgues, Marshonna

AU - Pomyen, Yotsawat

AU - Bhudhisawasdi, Vajarabhongsa

AU - Lertprasertsuke, Nirush

AU - Chotirosniramit, Anon

AU - Pairojkul, Chawalit

AU - Auewarakul, Chirayu U

AU - Sricharunrat, Thaniya

AU - Phornphutkul, Kannika

AU - Sangrajrang, Suleeporn

AU - Cam, Maggie

AU - He, Ping

AU - Hewitt, Stephen M

AU - Ylaya, Kris

AU - Wu, Xiaolin

AU - Andersen, Jesper B

AU - Thorgeirsson, Snorri S

AU - Waterfall, Joshua J

AU - Zhu, Yuelin J

AU - Walling, Jennifer

AU - Stevenson, Holly S

AU - Edelman, Daniel

AU - Meltzer, Paul S

AU - Loffredo, Christopher A

AU - Hama, Natsuko

AU - Shibata, Tatsuhiro

AU - Wiltrout, Robert H

AU - Harris, Curtis C

AU - Mahidol, Chulabhorn

AU - Ruchirawat, Mathuros

AU - Wang, Xin W

N1 - Published by Elsevier Inc.

PY - 2017/7/10

Y1 - 2017/7/10

N2 - 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. Chaisaingmongkol et al. identify common molecular subtypes linked to similar prognosis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma, clinically different malignancies, among Thai patients. These molecular subtypes are also found in other Asian patients, but rarely in Caucasian patients.

AB - 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. Chaisaingmongkol et al. identify common molecular subtypes linked to similar prognosis in intrahepatic cholangiocarcinoma and hepatocellular carcinoma, clinically different malignancies, among Thai patients. These molecular subtypes are also found in other Asian patients, but rarely in Caucasian patients.

KW - Asian Continental Ancestry Group

KW - Carcinoma, Hepatocellular

KW - Cholangiocarcinoma

KW - Cluster Analysis

KW - Humans

KW - Kaplan-Meier Estimate

KW - Liver Neoplasms

KW - Prognosis

KW - Transcriptome

KW - Journal Article

U2 - 10.1016/j.ccell.2017.05.009

DO - 10.1016/j.ccell.2017.05.009

M3 - Journal article

C2 - 28648284

SN - 1535-6108

VL - 32

SP - 57-70.e3

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Abstract

Keywords

UN SDGs

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