Nishihara, Hiroshi



School of Medicine, Clinical and Translational Research Center Genomics Unit, Keio Cancer Center, Keio University Graduate School of Medicine (Shinanomachi)



Related Websites

Contact Address

35 Shinanomachi, Shinjukuku, Tokyo, Japan

Telephone No.


Fax No.


Profile 【 Display / hide

  • 学 歴
    1995年(平成7年)3月 北海道大学医学部卒業(医学士)
    1999年(平成11年)3月 北海道大学大学院医学研究科 病理系専攻医学博士課程修了、学位取得(博士(医学))
    2002年(平成14年)3月 ~ 2004年(平成16年)7月
    Molecular pharmacology at University of California, San Diego, Department of Pharmacology (Dr. Paul A. Insel; as a research fellow)

    職 歴
    1999年(平成11年)4月 北海道大学医学部附属病院 病理部 (医員)
    2000年(平成12年)4月 北海道大学大学院医学研究科 分子細胞病理学 (助手)
    2008年(平成20年)10月 北海道大学大学院医学研究科 探索病理学講座 (特任准教授)
    2012年(平成24年)11月 北海道大学病院臨床研究開発センター 生体試料管理室 (室長(兼任))
    2015年(平成27年)1月 北海道大学大学院医学研究科探索病理学講座 (特任教授)
    2016年(平成28年)4月 北海道大学病院がん遺伝子診断部 (統括マネージャー(兼任))
    2017年(平成29年)4月 国立病院機構 北海道がんセンター がんゲノム医療センター(センター長)
    北海道大学病院 がん遺伝子診断部 客員教授(兼任;2018年3月まで)
    札幌医科大学医学部 客員教授(兼任;2019年3月まで)
         長崎大学医学部 客員教授(兼任)
    2017年(平成29年)7月 慶應義塾大学医学部 客員教授(兼任) 腫瘍センターゲノム医療ユニット  
    2017年(平成29年)11月 慶應義塾大学医学部 特任教授 腫瘍センターゲノム医療ユニット長
    社会医療法人北斗 北斗病院 病理・遺伝子診断科長(兼任)
    2018年(平成30年)10月 鹿児島大学医学部 客員教授(兼任)
    2019年(平成31年)4月  慶應義塾大学医学部 教授 臨床研究推進センター・腫瘍センターゲノム医療ユニット
    筑波大学医学部 客員教授(兼任)

Academic Background 【 Display / hide

  • 1989.04

    Hokkaido University, 医学部, 医学科

    日本, University, Graduated, Master's course

  • 1995.04

    Hokkaido University, 大学院, 医学研究科

    日本, Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Hokkaido University, Coursework, 1999.03

Licenses and Qualifications 【 Display / hide

  • 医師, 医師, 1995.04


Papers 【 Display / hide

  • 【大腸癌診療におけるprecision medicine】ゲノム解析を利用した大腸癌原発巣およびその肝転移巣に対するprecision medicine

    川俣 太, Patch Ann-Marie, Nones Katia, 本間 重紀, 西原 広史, 神山 俊哉, 武冨 紹信, Leggett Barbara, Waddell Nicola, Whitehall Vicki

    癌の臨床 ((株)篠原出版新社)  65 ( 4 ) 373 - 382 2021.01

    ISSN  0021-4949

     View Summary

    ゲノム解析を利用して同一患者の大腸癌原発巣と肝転移巣を比較検討し、化学療法の治療経過や転移過程における時空間的なゲノム変異の解明を試みた。その結果、臨床的に「actionable」な大腸癌ドライバー遺伝子が大腸癌と転移巣間では異なり、原発巣の病理結果から再発・転移巣に対する化学療法を選択しても、再発・転移巣には化学療法が奏功しない可能性が考えられた。また、ドライバー遺伝子の相違は原発巣から転移巣における治療過程でのclonal evolutionによって引き起こされることから、治療経過における転移巣切除や肝生検、リキッドバイオプシーを積極的に行うことで、より正確な真の癌個別化医療が進んでいくものと示唆された。

  • Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis

    Nakajima T., Yokota T., Shingu Y., Yamada A., Iba Y., Ujihira K., Wakasa S., Ooka T., Takada S., Shirakawa R., Katayama T., Furihata T., Fukushima A., Matsuoka R., Nishihara H., Dela F., Nakanishi K., Matsui Y., Kinugawa S.

    Scientific Reports (Scientific Reports)  9 ( 1 ) 3535 - 3535 2019.12

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2019, The Author(s). Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n = 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis.

  • A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation

    Kosaka T., Hongo H., Aimono E., Matsumoto K., Hayashida T., Mikami S., Nishihara H., Oya M.

    Pathology International (Pathology International)  69 ( 12 ) 715 - 720 2019.12

    Joint Work, Accepted,  ISSN  13205463

     View Summary

    © 2019 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Germline mutations and copy number changes in DNA damage repair (DDR) genes such as BRCA2 are associated with aggressive forms of prostate cancer (PCa). Although the prevalence of BRCA2 variants in PCa is increasing in Japan, the genomic and biological implications in Japanese patients are unclear. An 81-year-old male presented with prostatic adenocarcinoma with neuroendocrine differentiation accompanied by metastatic lung nodule and brain metastases. Platinum-based doublet chemotherapy combined with etoposide resulted in partial and complete remissions of brain and lung metastases, respectively. Next-generation sequencing of biopsy and peripheral blood samples demonstrated a somatic BRCA2 mutation at c.7008-2A>C and a germline mutation at p.E2877*. The patient's son had been diagnosed with breast cancer 2.5 years ago and was found to have the same germline BRCA2 mutation. BRCA2 mutation increases the risks of aggressive PCa and other cancer types in Japanese males. These forms may be highly responsive to platinum-based chemotherapy.

  • Cancer gene profiling explores the possible precision medicine for diffuse-type gastric adenocarcinoma.

    Marin Ishikawa, Hideyuki Hayashi, Naoya Sakamoto, Shinya Tanaka, Hiroshi Nishihara

    Medical oncology (Northwood, London, England) 37 ( 1 ) 10 - 10 2019.11

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Diffuse type gastric cancer (DGC), a pathological subtype, is one of the most common malignant solid tumors, and mortality of this tumor is not negligible, especially in early-onset cancer patients. In fact, affirmative personalized treatments based on gene profile have not been established yet. The aim of this study was to provide the possible genotype-matched treatment for DGC through comprehensive examination of genomic variants and analysis of clinicopathological characteristics. We retrospectively studied 23 formalin-fixed, paraffin-embedded samples of patients diagnosed as DGC between January 2003 and December 2015 at the Department of Cancer Pathology, Hokkaido University Graduate School of Medicine. The cases were divided into two groups: early-onset (< 50 years old) and elderly-onset (≥ 50 years old) DGC groups. We performed targeted genomic sequencing using a 163 cancer-related gene panel. The sequencing data were analyzed using an original bioinformatics pipeline called GenomeJack and were clinicopathologically evaluated. Intestinal metaplasia and atrophy were highly observed in the adjacent non-cancerous mucosa in the elderly-onset DGC group compared with those in the early-onset DGC group. The number of somatic variants was significantly higher in the elderly-onset DGC group than in the early-onset DGC group. Fifteen patients (65.2%) harbored at least one genomic alteration of the potential target for genotype-matched treatment. In addition, one patient with hypermutation phenotype was diagnosed as Lynch syndrome due to MLH1 mutation, suggesting the sensitivity for the treatment with immune checkpoint inhibitors. Not only does our study demonstrated the potential utility of the targeted genomic sequencing approach for making informed therapeutic decisions, but it also sheds light on DGC pathogenesis and progression.

  • Establishment of permutation for cancer risk estimation in the urothelium based on genome-wide DNA methylation analysis

    Tsumura K., Arai E., Tian Y., Shibuya A., Nishihara H., Yotani T., Yamada Y., Takahashi Y., Maeshima A.M., Fujimoto H., Nakagawa T., Kume H., Homma Y., Yoshida T., Kanai Y.

    Carcinogenesis (Carcinogenesis)  40 ( 11 ) 1308 - 1319 2019.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  01433334

     View Summary

    © 2019 The Author(s). Published by Oxford University Press. All rights reserved. The aim of this study was to establish permutation for cancer risk estimation in the urothelium. Twenty-six samples of normal control urothelium obtained from patients without urothelial carcinomas (C), 47 samples of non-cancerous urothelium without noticeable morphological changes obtained from patients with urothelial carcinomas (N), and 46 samples of the corresponding cancerous tissue (T) in the learning cohort and 64 N samples in the validation cohort, i.e. 183 tissue samples in total, were analyzed. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation 450K BeadChip, and DNA methylation levels were verified using pyrosequencing and MassARRAY. Amplicon sequencing was performed using the GeneRead DNAseq Targeted Panels V2. Although N samples rarely showed genetic mutations or copy number alterations, they showed DNA methylation alterations at 2502 CpG sites compared to C samples, and such alterations were inherited by or strengthened in T samples, indicating that DNA methylation alterations may participate in field cancerization in the urothelium. Receiver operating characteristic curve analysis confirmed the feasibility of cancer risk estimation to identify urothelium at the precancerous stage by DNA methylation quantification. Cancer risk estimation permutation was established using a combination of two marker CpG loci on the HOXC4, TENM3 and TLR1 genes (sensitivity and specificity 96-100%). Among them, the diagnostic impact of 10 patterns of permutation was successfully validated in the validation cohort (sensitivity and specificity 94-98%). These data suggest that cancer risk estimation using procedures such as urine tests during health checkups might become applicable for clinical use.

display all >>

Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 癌ゲノム医療 慶應義塾大学病院における脳腫瘍に対する網羅的がん遺伝子パネル検査 難治性髄膜腫を中心に

    藏成 勇紀, 笹尾 亮太, 四十物 絵理子, 中村 康平, 林 秀幸, 戸田 正博, 西原 広史, 佐々木 光

    Brain Tumor Pathology (日本脳腫瘍病理学会)  38 ( Suppl. ) 067 - 067 2021.05

    ISSN  1433-7398

  • HRAS変異を有する表皮母斑上に生じた多発有棘細胞癌

    柳 輝希, 北村 真也, 前田 拓哉, 奈良平 敦司, 氏家 英之, 西原 広史, 慶応義塾大学医学部腫瘍センターゲノム医療ユニット

    日本皮膚科学会雑誌 ((公社)日本皮膚科学会)  131 ( 5 ) 1404 - 1404 2021.05

    ISSN  0021-499X

  • 【日本人の疾患と健康のためのバイオバンクとデータベース活用法 試料と情報の的確な探し方と使い方】(第1章)バイオバンクプロジェクトの全体像 診療施設併設型バイオバンク(クリニカルバイオバンク)の機能と役割

    西原 広史

    実験医学 ((株)羊土社)  39 ( 7 ) 1041 - 1046 2021.05

    ISSN  0288-5514

     View Summary


  • いま知っておきたい最新の臨床検査 身近な疾患を先端技術で診断(Vol.1) がんゲノムプロファイリング検査

    西原 広史

    医学のあゆみ (医歯薬出版(株))  276 ( 13 ) 1205 - 1213 2021.03

    ISSN  0039-2359

     View Summary


  • ゲノム医療が切り拓くがん治療

    西原 広史

    日本内科学会雑誌 ((一社)日本内科学会)  110 ( 3 ) 511 - 519 2021.03

    ISSN  0021-5384

display all >>

Research Projects of Competitive Funds, etc. 【 Display / hide

  • Gene profiling for pressure ulcer


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 西原 広史, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • Clinical Sequence Platform for Brain Tumor


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 西原 広史, Grant-in-Aid for Scientific Research (C), Principal Investigator