Innovation and clinical application of lung cancer screening modality using microbead-based technology

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15H03034
• Research Institution: Kawasaki Medical School
• Principal Investigator: 永坂 岳司 川崎医科大学, 医学部, 准教授 (30452569)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 検査・診断システム / 腫瘍診断学 / 腫瘍検査学 / エピゲノム

Outline of Annual Research Achievements

本研究は喀痰に含まれる腫瘍由来Free核酸に認められる腫瘍特異的メチル化CpGを効率よく精確かつMechanicalに検出を行う技術の開発を行い，現状の肺がん検診ツールのイノベーションとその臨床応用を行うことを目的とする。平成29年度の研究実績の概要を以下に示す。
①The Cancer Genome Atlas (TCGA) から肺がんや正常肺組織のメチル化アレイを用いたデータを参考に，喀痰からの肺がんスクリーニングに用いるマーカーの検討を平成28年度に施行し、その再現性の確認を組織を用い行なった。②xMAP/MAGPIXでは検出可能CpGサイトが50と限りがあるためLuminex200に設定を変更し、合計76CpGsの解析を可能とするアッセイの構築を行なった。③平成２８年度にて解析を行なった合計209例のTestグループと合計202例のValidationグループの喀痰を用い、Luminex200によるアッセイ系を用い再検討を行なった。④肺がん患者に対するAUCはTestグループ＝0.944、Validationグループ＝0.932と著しい再現性を認めた。⑤これら結果をもとに，Luminex200によるアッセイ系の特許の作成を開始。⑥論文化の施行。⑦また、気管支内視鏡による侵襲的精査だけでは肺癌を確定できなかった症例 (切除またはその他の手段により確定を得た症例) は約10％存在したが、その症例の喀痰からもメチル化CpGはLuminex200では再現性をもって検出されていたという結果を習得し、今後の展開を行う橋渡し研究の構築を開始した。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] BRAF V600E mutation is a predictive indicator of upfront chemotherapy for stage IV colorectal cancer. (2018)
  • Author(s): Morikawa T, Inada R, Nagasaka T, Mori Y, Kishimoto H, Kawai T, Umeda Y, Mishima H, Goel A, Fujiwara T
  • Journal Title: Oncology Letters Volume: 15 Pages: 2195-2201
  • DOI: 10.3892/ol.2017.7553
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors. (2018)
  • Author(s): Takehara Y, Nagasaka T, Nyuya A, Haruma T, Haraga J, Mori Y, Nakamura K, Fujiwara T, Boland CR, Goel A.
  • Journal Title: J Transl Med. Volume: 16 Pages: 5
  • DOI: 10.1186/s12967-017-1376-4.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles. (2018)
  • Author(s): Mori Y, Nyuya A, Yasui K, Toshima T, Kawai T, Taniguchi F, Kimura K, Inada R, Nishizaki M, Haraga J, Nakamura K, Umeda Y, Kishimoto H, Fujiwara T, Katata Y, Yamaguchi Y, Nagasaka T
  • Journal Title: Oncotarget Volume: 27 Pages: 16477-16488
  • DOI: 10.18632/oncotarget.24735
  • Peer Reviewed / Open Access
• [Journal Article] Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability. (2018)
  • Author(s): Haruma T, Nagasaka T, Nakamura K, Haraga J, Nyuya A, Nishida T, Goel A, Masuyama H, Hiramatsu Y.
  • Journal Title: PLoS One Volume: 13 Pages: e0195655
  • DOI: 10.1371/journal.pone.0195655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk Analysis for Invasive Fungal Infection after Living Donor Liver Transplantation: Which Patient Needs Potent Prophylaxis? (2018)
  • Author(s): Utsumi M, Umeda Y, Yagi T, Nagasaka T, Shinoura S, Yoshida R, Nobuoka D, Kuise T, Fuji T, Takagi K, Takaki A , Fujiwara T.
  • Journal Title: Dig Surg Volume: 不明 Pages: Apr 12
  • DOI: 10.1159/000486548
  • Peer Reviewed
• [Journal Article] Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer. (2018)
  • Author(s): Yoshioka T, Shien K, Namba K, Torigoe H, Sato H, Tomida S, Yamamoto H, Asano H, Soh J, Tsukuda K, Nagasaka T, Fujiwara T, Toyooka S
  • Journal Title: Cancer Sci Volume: 109 Pages: 1166-1176
  • DOI: 10.1111/cas.13546
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. (2018)
  • Author(s): Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, Wei Q, Qin H, Lin H, Ma Y, Goel A.
  • Journal Title: Mol Cancer Volume: 30 Pages: 16
  • DOI: 0.1186/s12943-018-0767-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of outcomes between symptomatic and asymptomatic patients with colorectal cancer: a propensity score-matched analysis of surgical invasiveness, medical costs and oncological outcomes. (2017)
  • Author(s): Inada R, Nagasaka T, Watanabe A, Yagi T, Mori Y, Kondo Y, Kishimoto H, Umeda Y, Fujiwara T.
  • Journal Title: BMJ Open Gastroenterol. Volume: 4 Pages: e000146
  • DOI: 10.1136/bmjgast-2017-000146.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation. (2017)
  • Author(s): Yoshida K, Umeda Y, Takaki A, Nagasaka T, Yoshida R, Nobuoka D, Kuise T, Takagi K, Yasunaka T, Okada H, Yagi T, Fujiwara T.
  • Journal Title: Acta Med Okayama Volume: 71 Pages: 381-390
  • DOI: 10.18926/AMO/55435
  • Peer Reviewed
• [Journal Article] SNORA21 - An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer. (2017)
  • Author(s): Yoshida K, Toden S, Weng W, Shigeyasu K, Miyoshi J, Turner J, Nagasaka T, Ma Y, Takayama T, Fujiwara T, Goel A.
  • Journal Title: EBioMedicine Volume: 22 Pages: 68-77
  • DOI: 10.1016/j.ebiom.2017.07.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circular RNA ciRS-7-A Promising Prognostic Biomarker and a Potential Therapeutic Target in Colorectal Cancer. (2017)
  • Author(s): Weng W, Wei Q, Toden S, Yoshida K, Nagasaka T, Fujiwara T, Cai S, Qin H, Ma Y, Goel A.
  • Journal Title: Clin Cancer Res Volume: 15 Pages: 3918-3928
  • DOI: 10.1158/1078-0432.CCR-16-2541
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. (2017)
  • Author(s): Okugawa Y, Toiyama Y, Toden S, Mitoma H, Nagasaka T, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A.
  • Journal Title: Gut. Volume: 66 Pages: 107-117
  • DOI: 10.1136/gutjnl-2015-309359.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adenocarcinoma in the jejunum 20 years after surgery for familial adenomatous polyposis (2017)
  • Author(s): Yuusaku Sugihara. Seiji Kawano, Keita Harada, Shiho Takashima, Daisuke Takei, Toshihiro Inokuchi, Masahiro Takahara, Sakiko Hiraoka, Yoshiko Mori, Hiroyuki Kishimoto, Takeshi Nagasaka, Hiroyuki Okada
  • Journal Title: Okayama Igakkai Zasshi Volume: 129 Pages: 111-114
  • DOI: 10.4044/joma.129.111
  • Peer Reviewed
• [Presentation] Primary Tumor Location と Genetic/Epigenetic 変異分布不均衡に対する検討 (2018)
  • Author(s): 永坂 岳司1、堅田 洋佑1、岡脇 誠1、山村 真弘1、母里 淑子2、安井 和也2、戸嶋 俊明2、岸本 浩行2、藤原 俊儀2、山口 佳之1
  • Organizer: 第８８回大腸癌研究会
• [Presentation] 大腸癌1070例の遺伝子変異情報を含めた臨床予後解析結果 (2017)
  • Author(s): 永坂 岳司（岡山大学、川崎医科大学） [共著者] 母里 淑子（岡山大学） 重安 邦俊（岡山大学） 河合 毅（岡山大学） 岸本 浩行（岡山大学） 藤原 俊儀（岡山大学） 山口 佳之（川崎医科大学）
  • Organizer: 第72回日本大腸肛門病学会学術集会
• [Presentation] A Novel Circulating Cell Free DNA-Based Assay Can Predict Tumor Response to Systematic Chemotherapy (2017)
  • Author(s): T. Toshima, T. Nagasaka, Y. Mori, T. Kawai, K. Yasui, T. Fuji, F. Taniguchi, K. Kimura, H. Kishimoto, Y. Umeda, A. Goel, T. Fujiwara
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] Heterogenity of epigenetic and EMT marks observed in hepatocellular carcinoma with keratin 19 proficiency (2017)
  • Author(s): Nagasaka T, Okada T, Yokomichi N, Taniguchi F, Toshima T, Yasui K, Fuji T, Mori Y, Kawai T, Umeda Y, Yagi T, Fujiwara T, Goel A
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] Multicenter phase II study of biweekly XELIRI plus Bevacizumab as a second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study) (2017)
  • Author(s): Y. Mori, N. Suzuki, T. Nagasaka, H. Tanioka, Y. Iwamoto, Y. Neki, T. Yamatsuji, M. Kobayashi, M. Nakajima, Y. Ojima, S. Ikeda, K. Kawamoto, K. Shinozaki, A. Tsuji, T. Hinoi, Y. Yamaguchi, K. Yamashita, M. Shimokawa, M. Okajima, S. Hazama
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] Gene expression signatures in BRAF V600E mutant colorectal cancer in relation to WNT signaling cascade (2017)
  • Author(s): asui K, Nagasaka T, Nyuya A, Toshima T, Kawai T, Shigeyasu K, Yano S, Mori Y, Haraga J, Nakamura K, Umeda Y, Goel A, Fujiwara T
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] POLE mutations and MSI were positive predictive factors for progression free survival in endometrial cancer patients at the risk of recurrence (2017)
  • Author(s): A. Nyuya, J. Haraga, Takeshi Nagasaka, K. Nakamura, T. Haruma, T. Nishida, K. Yasui, T. Fujiwara, Ajay Goel, H. Masuyama
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] Significance of MSH2 promoter methylation in endometrial cancer with MSH2 deficiency (2017)
  • Author(s): J. Haraga, Takeshi Nagasaka, K. Nakamura, A. Nyuya, T. Haruma, T. Nishida, K. Yasui, T. Fujiwara, Ajay Goel, H. Masuyama
  • Organizer: ESMO 2017 Congress
  • Int'l Joint Research
• [Presentation] Fine Mapping of a Critical Genetic Element for Liver Metasasis from Primary Colorectal Cancer (CRC) within the HIF3A Locus (2017)
  • Author(s): Carlos Zavala, Minoru Koi, Takahito Kitajima, Kazuya Yasui, Takeshi Nagasaka, Chan Choi, Hyeong-Rok Kim, Yuji Toiyama, John M. Carethers
  • Organizer: DDW2017
  • Int'l Joint Research
• [Presentation] Ovarian metastasectomy in colorectal cancer may improve the clinical outcomes of patients with metastatic colorectal cancer regardless of BRAF or KRAS mutational profiles (2017)
  • Author(s): Yoshiko Mori, Takeshi Nagasaka, Hiroaki Tanioka, Akihiro Nyuya, Takashi Kawai, Toshiaki Toshima, Kazuya Yasui, Kunitoshi Shigeyasu, Hiroyuki Kishimoto, Yuzo Umeda, Toshiyoshi Fujiwara
  • Organizer: ESMO-GI 2017
  • Int'l Joint Research
• [Presentation] The clinical predictor of antitumor efficacy of cetuximab retreatment in patients with metastatic colorectal cancer who had a clinical benefit in response to prior cetuximab based regimen (2017)
  • Author(s): Hiroaki Tanioka, Motoi Asano, Ryousuke Yoshida, Naohisa Waki, Masahiro Ishizaki, Kazuki Yamashita, Yoshiko Mori, Takeshi Nagasaka,
  • Organizer: ESMO-GI 2017
  • Int'l Joint Research
• [Presentation] Novel theranostic strategy against scirrhous gastric cancer; combination of chemotherapy and fluorescence oncolytic adenovirus (2017)
  • Author(s): Wataru Ishikawa, Satoru Kikuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] Novel evidence for AZIN1 RNA editing-mediated oncogenic role in colorectal cancer (2017)
  • Author(s): Kunitoshi Shigeyasu, Shusuke Toden, Yoshinaga Okugawa, Jinsei Miyoshi, Takeshi Nagasaka, Toshiyoshi Fujiwara, Leilei Chen, Ajay Goel
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] Gene expression profiles in BRAF V600E mutant colorectal cancer and association with SFRP2 methylation status (2017)
  • Author(s): Kazuya Yasui, Takeshi Nagasaka, Toshiaki Toshima, Takashi Kawai, Kunitoshi Shigeyasu, Yoshiko Mori, Junko Haraga, Keiichiro Nakamura, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] Fluorescence-guided spatiotemporal dynamics of epithelial-mesenchymal transition under inflammatory microenvironment during colorectal cancer progression (2017)
  • Author(s): Takeshi Ieda, Hiroshi Tazawa, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Takeshi Imamura, Toshiyoshi Fujiwara
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] Clinicopathological significance of endometrial cancer with MSH2 deficiency (2017)
  • Author(s): Junko Haraga, Takeshi Nagasaka, Keiichirou Nakamura, Tomoko Haruma, Takeshi Nishida, Akihiro Nyuya, Kazuya Yasui, Hisashi Masuyama, Toshiyoshi Fujiwara, Yuji Hiramatsu
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] Hyperthermia at the single-cell level for disseminated cancer disease with immuno-magnetic nanoparticles (2017)
  • Author(s): Tetsuya Kagawa, Hiroyuki Kishimoto, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Takeshi Nagasaka, Satoshi Nohara, Ichiro Kato, Adarsh Sandhu, Hiromichi Aono, Toshiyoshi Fujiwara
  • Organizer: AACR2017
  • Int'l Joint Research
• [Presentation] 遺伝子変異情報に基づいた大腸癌肝転移の治療戦略―原発巣の左右局在とRAS/RAF 変異の意義― (2017)
  • Author(s): 楳田祐三, 永坂岳司, 母里淑子, 吉田龍一, 信岡大輔, 杭瀬 崇, 藤 智和, 河合 毅, 荒木宏之, 八木孝仁, 藤原俊義
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] StageIV大腸癌に対するPrecision Medicineの構築 (2017)
  • Author(s): 河合 毅, 永坂岳司, 母里淑子, 楳田祐三, 稲田 涼, 谷口文崇, 安井和也, 戸嶋俊明, 岸本浩行, 藤原俊義
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] utcome of locally advanced rectal cancer with or without preoperative treatments (2017)
  • Author(s): 母里淑子, 永坂岳司, 稲田 涼, 河合 毅, 近藤喜太, 浅野博昭, 佃 和憲, 木村圭佑, 楳田祐三, 岸本浩行, 藤原俊義
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 便中メチル化CpG検出による非侵襲的大腸癌スクリーニング技術の実用化を目指して (2017)
  • Author(s): 永坂岳司, 母里淑子, 入谷光洋, 安井和也, 戸嶋俊明, 河合 毅, 重安邦俊, 谷口文崇, 藤 智和, 楳田祐三, 岸本浩行, 藤原俊義
  • Organizer: 第87回大腸癌研究会
• [Presentation] PVT1 は癌遺伝子MYC を駆動するエンハンサーでありStage II, III 大腸癌の予後予測マーカーになりうる (2017)
  • Author(s): 重安邦俊, 小澤穀士, 松山貴俊, 河合 毅, 矢野修也, 母里淑子, 岸本浩行, 永坂岳司, Goel A, 藤原俊義
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 大腸癌多発肝転移におけるRAS/RAF変異の意義～生物学的悪性度から術前化学療法適応を見極める～ (2017)
  • Author(s): 楳田祐三, 八木孝仁, 永坂岳司, 吉田龍一, 信岡大輔, 母里淑子, 杭瀬 崇, 高木弘誠, 河合 毅, 藤原俊義
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 局所進行直腸癌に対する術前化学療法の有用性 (2017)
  • Author(s): 母里淑子, 永坂岳司, 河合 毅, 重安邦俊, 矢野修也, 近藤喜太, 楳田祐三, 岸本浩行, 藤原俊義
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] Lynch Syndrome に対する化学療法 (2017)
  • Author(s): 母里淑子, 永坂岳司, 角田美穂, 山口達郎, 田中屋宏爾, 山下健太郎, 野水整, 檜井孝夫, 石田秀行, 赤木究
  • Organizer: 第15回日本臨床腫瘍学会学術集会
• [Presentation] Clinical prevalence of microsatellite instability colorectal cancer and lynch syndrome cancer (2017)
  • Author(s): 永坂岳司, 母里淑子, 重安邦俊, 原賀順子, 谷口文崇, 藤原俊義
  • Organizer: 第23回家族性腫瘍学会学術集会
• [Presentation] ミスマッチ修復の観点からみた、大腸癌におけるExportin-5 の臨床的意義 (2017)
  • Author(s): 重安邦俊, 奥川喜永, 母里淑子, 安井和也, 入谷光洋, 河合 毅, 矢野修也, 岸本浩行, 永坂岳司, 香川俊輔, Goel A, 藤原俊義
  • Organizer: 第23回家族性腫瘍学会学術集会
• [Presentation] 切除不能進行再発大腸がんの２次治療以降における Ramcirumab + FOLFIRI 療法の治療成績 (2017)
  • Author(s): 永坂岳司, 母里淑子, 重安邦俊, 河合 毅, 矢野修也, 岸本浩行, 楳田祐三, 山口佳之, 藤原俊義
  • Organizer: 第55回日本癌治療学会学術集会
• [Presentation] 遅発性に肝転移・骨盤内リンパ節転移をきたした直腸神経内分泌腫瘍の1例 (2017)
  • Author(s): 重安邦俊, 杭瀬 崇, 母里淑子, 河合 毅, 矢野修也, 戸嶋俊明, 浅野博昭, 近藤喜太, 佃 和憲, 永坂岳司, 八木孝仁, 藤原俊義
  • Organizer: 第72回日本大腸肛門病学会学術集会