Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Ruidong Xue; Lu Chen; Chong Zhang; Masashi Fujita; Ruoyan Li; Shu Mei Yan; Choon Kiat Ong; Xiwen Liao; Qiang Gao; Shota Sasagawa; Yanmeng Li; Jincheng Wang; Hua Guo; Qi Tao Huang; Qian Zhong; Jing Tan; Lisha Qi; Wenchen Gong; Zhixian Hong; Meng Li; Jingmin Zhao; Tao Peng; Yinying Lu; Kiat Hon Tony Lim; Arnoud Boot; Atushi Ono; Kazuaki Chayama; Zemin Zhang; Steve George Rozen; Bin Tean Teh; Xin Wei Wang; Hidewaki Nakagawa; Mu Sheng Zeng; Fan Bai; Ning Zhang

doi:10.1016/j.ccell.2019.04.007

Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Ruidong Xue, Lu Chen, Chong Zhang, Masashi Fujita, Ruoyan Li, Shu Mei Yan, Choon Kiat Ong, Xiwen Liao, Qiang Gao, Shota Sasagawa, Yanmeng Li, Jincheng Wang, Hua Guo, Qi Tao Huang, Qian Zhong, Jing Tan, Lisha Qi, Wenchen Gong, Zhixian Hong, Meng LiJingmin Zhao, Tao Peng, Yinying Lu, Kiat Hon Tony Lim, Arnoud Boot, Atushi Ono, Kazuaki Chayama, Zemin Zhang, Steve George Rozen, Bin Tean Teh, Xin Wei Wang, Hidewaki Nakagawa^*, Mu Sheng Zeng, Fan Bai, Ning Zhang

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

213 Scopus citations

Abstract

We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC. Xue et al. perform genomic and transcriptomic analyses of combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC). They show that combined and mixed types of cHCC-ICC have different clinical and molecular features and that Nestin expression may be a diagnostic biomarker for cHCC-ICC.

Original language	English
Pages (from-to)	932-947.e8
Journal	Cancer Cell
Volume	35
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2019.04.007
State	Published - 10 06 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Allen and Lisa
bilinear differentiation
clonal origin
intratumor heterogeneity
liver cancer
metastatic route
molecular subtype
Nestin
phenotypic transition
single nucleus sequencing

UN SDGs

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

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10.1016/j.ccell.2019.04.007

Cite this

Xue, R., Chen, L., Zhang, C., Fujita, M., Li, R., Yan, S. M., Ong, C. K., Liao, X., Gao, Q., Sasagawa, S., Li, Y., Wang, J., Guo, H., Huang, Q. T., Zhong, Q., Tan, J., Qi, L., Gong, W., Hong, Z., ... Zhang, N. (2019). Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes. Cancer Cell, 35(6), 932-947.e8. https://doi.org/10.1016/j.ccell.2019.04.007

@article{fbad4486307d4965b470652f2631914c,

title = "Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes",

abstract = "We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC. Xue et al. perform genomic and transcriptomic analyses of combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC). They show that combined and mixed types of cHCC-ICC have different clinical and molecular features and that Nestin expression may be a diagnostic biomarker for cHCC-ICC.",

keywords = "Allen and Lisa, bilinear differentiation, clonal origin, intratumor heterogeneity, liver cancer, metastatic route, molecular subtype, Nestin, phenotypic transition, single nucleus sequencing",

author = "Ruidong Xue and Lu Chen and Chong Zhang and Masashi Fujita and Ruoyan Li and Yan, {Shu Mei} and Ong, {Choon Kiat} and Xiwen Liao and Qiang Gao and Shota Sasagawa and Yanmeng Li and Jincheng Wang and Hua Guo and Huang, {Qi Tao} and Qian Zhong and Jing Tan and Lisha Qi and Wenchen Gong and Zhixian Hong and Meng Li and Jingmin Zhao and Tao Peng and Yinying Lu and Lim, {Kiat Hon Tony} and Arnoud Boot and Atushi Ono and Kazuaki Chayama and Zemin Zhang and Rozen, {Steve George} and Teh, {Bin Tean} and Wang, {Xin Wei} and Hidewaki Nakagawa and Zeng, {Mu Sheng} and Fan Bai and Ning Zhang",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = jun,

day = "10",

doi = "10.1016/j.ccell.2019.04.007",

language = "英语",

volume = "35",

pages = "932--947.e8",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

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Xue, R, Chen, L, Zhang, C, Fujita, M, Li, R, Yan, SM, Ong, CK, Liao, X, Gao, Q, Sasagawa, S, Li, Y, Wang, J, Guo, H, Huang, QT, Zhong, Q, Tan, J, Qi, L, Gong, W, Hong, Z, Li, M, Zhao, J, Peng, T, Lu, Y, Lim, KHT, Boot, A, Ono, A, Chayama, K, Zhang, Z, Rozen, SG, Teh, BT, Wang, XW, Nakagawa, H, Zeng, MS, Bai, F & Zhang, N 2019, 'Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes', Cancer Cell, vol. 35, no. 6, pp. 932-947.e8. https://doi.org/10.1016/j.ccell.2019.04.007

TY - JOUR

T1 - Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

AU - Xue, Ruidong

AU - Chen, Lu

AU - Zhang, Chong

AU - Fujita, Masashi

AU - Li, Ruoyan

AU - Yan, Shu Mei

AU - Ong, Choon Kiat

AU - Liao, Xiwen

AU - Gao, Qiang

AU - Sasagawa, Shota

AU - Li, Yanmeng

AU - Wang, Jincheng

AU - Guo, Hua

AU - Huang, Qi Tao

AU - Zhong, Qian

AU - Tan, Jing

AU - Qi, Lisha

AU - Gong, Wenchen

AU - Hong, Zhixian

AU - Li, Meng

AU - Zhao, Jingmin

AU - Peng, Tao

AU - Lu, Yinying

AU - Lim, Kiat Hon Tony

AU - Boot, Arnoud

AU - Ono, Atushi

AU - Chayama, Kazuaki

AU - Zhang, Zemin

AU - Rozen, Steve George

AU - Teh, Bin Tean

AU - Wang, Xin Wei

AU - Nakagawa, Hidewaki

AU - Zeng, Mu Sheng

AU - Bai, Fan

AU - Zhang, Ning

PY - 2019/6/10

Y1 - 2019/6/10

N2 - We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC. Xue et al. perform genomic and transcriptomic analyses of combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC). They show that combined and mixed types of cHCC-ICC have different clinical and molecular features and that Nestin expression may be a diagnostic biomarker for cHCC-ICC.

AB - We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC. Xue et al. perform genomic and transcriptomic analyses of combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC). They show that combined and mixed types of cHCC-ICC have different clinical and molecular features and that Nestin expression may be a diagnostic biomarker for cHCC-ICC.

KW - Allen and Lisa

KW - bilinear differentiation

KW - clonal origin

KW - intratumor heterogeneity

KW - liver cancer

KW - metastatic route

KW - molecular subtype

KW - Nestin

KW - phenotypic transition

KW - single nucleus sequencing

UR - http://www.scopus.com/inward/record.url?scp=85066461090&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2019.04.007

DO - 10.1016/j.ccell.2019.04.007

M3 - 文章

C2 - 31130341

AN - SCOPUS:85066461090

SN - 1535-6108

VL - 35

SP - 932-947.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Abstract

Bibliographical note

Keywords

UN SDGs

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