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, Hidewaki Nakagawa

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number6481
JournalNature communications
Issue number1
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)


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