Oncotarget

Research Papers:

Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase

Yuki Okawa _, Nobutaka Ebata, Nayoung K.D. Kim, Masashi Fujita, Kazuhiro Maejima, Shota Sasagawa, Toru Nakamura, Woong-Yang Park, Satoshi Hirano and Hidewaki Nakagawa

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Oncotarget. 2021; 12:1540-1552. https://doi.org/10.18632/oncotarget.28021

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Abstract

Yuki Okawa1,2, Nobutaka Ebata1,2, Nayoung K.D. Kim3,4, Masashi Fujita1, Kazuhiro Maejima1, Shota Sasagawa1, Toru Nakamura2, Woong-Yang Park3,4, Satoshi Hirano2 and Hidewaki Nakagawa1

1 Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

2 Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan

3 Geninus Inc., Seoul, Republic of Korea

4 Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea

Correspondence to:

Hidewaki Nakagawa,email: [email protected]
Satoshi Hirano,email: [email protected]

Keywords: biliary tract cancer; mutation; immunotherapic biomarker; knowledgebase; molecular targeted therapy

Received: April 30, 2021     Accepted: June 14, 2021     Published: July 20, 2021

Copyright: © 2021 Okawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Introduction: Treatment options for biliary tract cancer (BTC) are very limited. It is necessary to investigate actionable genes and candidate drugs using a sophisticated knowledgebase (KB) and characterize BTCs immunologically for evaluating the actionability of molecular and immune therapies.

Materials and Methods: The genomic and transcriptome data of 219 patients with BTC who underwent surgery were analyzed. Actionable mutations and candidate drugs were annotated using the largest available KB of the Asian population (CancerSCAN®). Predictive biomarkers of immune checkpoint inhibitors were analyzed using DNA and RNA sequencing data.

Results: Twenty-two actionable genes and 43 candidate drugs were annotated in 74 patients (33.8%). The most frequent actionable genes were PTEN (7.3%), CDKN2A (6.8%), KRAS (6.4%). BRCA2, CDKN2A, and FGFR2 mutations were most frequently identified in case of intrahepatic cholangiocarcinoma. PTEN and CDKN2A mutations were associated with significantly shorter overall survival. PD-L1 and PD-1 expression was significantly higher in case of extrahepatic cholangiocarcinoma and T-cell-high expression. In total, 49.7% of cases were evaluated as having actionability for molecular therapy or immune checkpoint inhibitors.

Conclusions: Identifying actionable genes and candidate drugs using the KB contribute to the development of therapeutic drugs and personalized treatment for BTC.


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