Next-generation sequencing approach to detect chemoradiotherapy response in esophageal cancer

• Project/Area Number: 26861003
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kyushu University
• Principal Investigator: Hirata Hidenari 九州大学, 大学病院, その他 (90721267)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 化学放射線感受性 / 遺伝子異常 / 食道癌 / エキソームシークエンス / RNAシークエンス / メチル化シークエンス / 化学放射線治療 / CRT / 食道扁平上皮癌

Outline of Final Research Achievements

Esophageal Squamous Cell Carcinoma(ESCC) is resistant to chemoradiotherapy (CRT); therefore, identification of useful biomarkers predicting CRT response is required. To determine whether gene alterations associate with response to CRT, next-generation sequencingt of ESCC treated with definitive CRT was performed. We carried out whole-exome sequencing, DNA methylation sequencing, and RNA sequencing of 6 pretreatment and 2 recurrent ESCCs. Then, gene alterations of CRT responders were compared with CRT nonresponders. We found that the presence of TP53 mutation could not predict clinical response to CRT. We will analyze in detail for genome, epigenome and transcriptome profiles of ESCC treated with definitive CRT.

Research Products

• [Journal Article] Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma (2016)
  • Author(s): Hirata H, Sugimachi K, Komatsu H, Ueda M, Masuda T, Uchi R, Sakimura S, Nambara S, Saito T, Shinden Y, Iguchi T, Eguchi H, Ito S, Terashima K, Sakamoto K, Hirakawa M, Honda H, Mimori K.
  • Journal Title: Cancer Res. Volume: in press
  • Peer Reviewed
• [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. (2016)
  • Author(s): G. Sawada (他43名, 山本21番目)
  • Journal Title: Gastroenterology Volume: 150 Issue: 5 Pages: 1171-1182
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. (2016)
  • Author(s): R. Uchi (他40名, 山本36番目)
  • Journal Title: PLoS Genetics Volume: 12 Issue: 2 Pages: 1-24
  • DOI: 10.1371/journal.pgen.1005778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma (2015)
  • Author(s): Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T, Takahashi Y, Kurashige J, Matsumura T, Ueo H, Takano Y, Ueda M, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Yamasaki M, Tanaka F, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Tanaka Y, Calin G, Miyano S, Doki Y, Mori M, Mimori K
  • Journal Title: PLoS One Volume: 10(10) Issue: 10 Pages: e0139808-e0139808
  • DOI: 10.1371/journal.pone.0139808
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy for lung tumors. (2015)
  • Author(s): Asai K, Nakamura K, Shioyama Y, Sasaki T, Matsuo Y, Ohga S, Yoshitake T, Terashima K, Shinoto M, Matsumoto K, Hirata H, Honda H.
  • Journal Title: Int J Clin Oncol Volume: epub Issue: 6 Pages: 1117-21
  • DOI: 10.1007/s10147-015-0833-4
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma. (2014)
  • Author(s): Hirata H, Sugimachi K, Takahashi Y, Ueda M, Sakimura S, Uchi R, Kurashige J, Takano Y, Nanbara S, Komatsu H, Saito T, Shinden Y, Iguchi T, Eguchi H, Atsumi K, Sakamoto K, Doi T, Hirakawa M, Honda H, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: epub Issue: S3 Pages: 1402-9
  • DOI: 10.1245/s10434-014-4242-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of CDCP1 expression promotes invasiveness and poor prognosis in esophageal squamous cell carcinoma. (2014)
  • Author(s): Sawada G, Takahashi Y, Niida A, Shimamura T, Kurashige J, Matsumura T, Ueo H, Uchi R, Takano Y, Ueda M, Hirata H, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Miyano S, Doki Y, Mori M, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: 4 Issue: S4 Pages: 640-647
  • DOI: 10.1245/s10434-014-3740-4
  • Peer Reviewed / Open Access
• [Presentation] Fructose-1,6-biphosphatase発現異常は肝癌の腫瘍進展・糖代謝異常に寄与する (2016)
  • Author(s): 平田 秀成、杉町 圭史、増田 隆明、林 直樹、井口 友宏、江口 英利、伊藤修平、寺嶋 広太郎、坂本 勝美、平川 雅和、本田 浩、三森 功士
  • Organizer: 第18回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2016-02-05
• [Presentation] 食道発癌・癌進展の宿主側・腫瘍側・疫学環境要因からの三位一体の解明 (2015)
  • Author(s): 平田秀成、三森功士
  • Organizer: がんゲノム・エピゲノムセミナー
  • Place of Presentation: 花巻
  • Year and Date: 2015-10-27
• [Presentation] FBP1 suppresses tumor progression and retrieves altered glucose metabolism in Hepatocellular carcinoma (2015)
  • Author(s): Hirata H, Sugimachi K, Komatsu H, Ueda M, Uchi R, Sakimura S, Masuda T, Iguchi T, Eguchi H, Ito S, Hirakawa M, Honda H, Mimori K.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Comprehensive Mutation Analysis of Response to Chemoradiothrapy in Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): H Hirata, R Uchi, M Ueda, S Sakimura, Y Shinden, T Iguchi, K Atsumi, D Tsurumaru, K Sakamoto, K Sugimachi, M Hirakawa, T Sasaki, K Nakamura, H Honda, K Mimori.
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] エキソームシークエンスによる食道癌化学放射線感受性の多様性を規定する網羅的変異解析 (2015)
  • Author(s): 平田秀成、内龍太郎、上田正射、﨑村正太郎、小松久晃、南原翔、齋藤衆子、新田吉陽、井口友宏、江口英利、杉町圭史、渥美和重、坂本一美、平川雅和、本田浩、三森功士
  • Organizer: 第17回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2015-02-02 – 2015-02-06
• [Presentation] Mutational Analysis of Peritoneal Disseminated Model in Gastric Adenocarcinoma (2014)
  • Author(s): Hirata H, Kurashige J, Sugimachi K, Uchi R, Ueda M, Sakimura S, Takano Y, Shinden Y, Iguchi T, Eguchi H, Hirakawa H, Honda H, Mimori M.
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 放射線腫瘍医として知っておきたい分子標的治療 －放射線治療との併用を中心に－ (2014)
  • Author(s): 平田秀成
  • Organizer: 第26回九州放射線治療セミナー
  • Place of Presentation: 福岡
  • Year and Date: 2014-08-09 – 2014-08-10
• [Presentation] Down-regulation of PRRX1 confers cancer stem cell-like properties and poor prognosis in hepatocellular carcinoma (2014)
  • Author(s): Hirata H, Sugimachi K, Uchi R, Kurashige J, Matsumura T, Ueo H, Takano Y, Ueda M, Sakimura S, Shinden Y, Eguchi H, Sudo T, Hirakawa M, Honda H, Mimori M.
  • Organizer: The 105th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-05 – 2014-04-09