Proteo-genomic characterization of virus-associated liver cancers reveals potential subtypes and therapeutic targets

Masashi Fujita, Mei-Ju May Chen, Doris Rieko Siwak, Shota Sasagawa, Ayako Oosawa-Tatsuguchi, Koji Arihiro, Atsushi Ono, Ryoichi Miura, Kazuhiro Maejima, Hiroshi Aikata, Masaki Ueno, Shinya Hayami, Hiroki Yamaue, Kazuaki Chayama, Ju-Seog Lee, Yiling Lu, Gordon B. Mills, Han Liang, Satoshi S. Nishizuka and Hidewaki Nakagawa ()
Additional contact information
Masashi Fujita: Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences
Mei-Ju May Chen: The University of Texas MD Anderson Cancer Center
Doris Rieko Siwak: The University of Texas MD Anderson Cancer Center
Shota Sasagawa: Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences
Ayako Oosawa-Tatsuguchi: Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences
Koji Arihiro: Hiroshima University Hospital
Atsushi Ono: Hiroshima University
Ryoichi Miura: Hiroshima University
Kazuhiro Maejima: Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences
Hiroshi Aikata: Hiroshima University
Masaki Ueno: Wakayama Medical University
Shinya Hayami: Wakayama Medical University
Hiroki Yamaue: Wakayama Medical University
Kazuaki Chayama: Hiroshima University
Ju-Seog Lee: The University of Texas MD Anderson Cancer Center
Yiling Lu: The University of Texas MD Anderson Cancer Center
Gordon B. Mills: Knight Cancer Institute, Oregon Health & Science University
Han Liang: The University of Texas MD Anderson Cancer Center
Satoshi S. Nishizuka: Iwate Medical University
Hidewaki Nakagawa: Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer subtype. Unsupervised classification of tumors based on protein expression profiles reveal three proteomic subclasses R1, R2, and R3. The R1 subclass is immunologically hot and demonstrated a good prognosis. R2 contains advanced proliferative tumor with TP53 mutations, high expression of VEGF receptor 2 and the worst prognosis. R3 is enriched with CTNNB1 mutations and elevated mTOR signaling pathway activity. Twenty-two proteins, including CDK1 and CDKN2A, are identified as potential prognostic markers. The proteomic classification presented in this study can help guide therapeutic decision making for liver cancer treatment.

Date: 2022
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DOI: 10.1038/s41467-022-34249-x

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