Exploratory analyses of comprehensive and quantitative mutation profiling using cell-free DNA

• Project/Area Number: 26870509
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; Tumor diagnostics
• Research Institution: Wakayama Medical University
• Principal Investigator: Akamatsu Hiroaki 和歌山県立医科大学, 医学部, 助教 (10646582)
• Co-Investigator(Renkei-kenkyūsha): KIKUCHI Takashi 和歌山県立医科大学, 内科学第3講座, 助教 (40649050) ; YAMAMOTO Nobuyuki 和歌山県立医科大学, 内科学第3講座, 教授 (60298966) ; KOH Yasuhiro 和歌山県立医科大学, 内科学第3講座, 講師 (80426519)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: リキッドバイオプシー / EGFR遺伝子変異 / 肺がん / liquid biopsy / Liquid Biopsyに関する研究

Outline of Final Research Achievements

To establish multiplex assay of EGFR mutation using digital PCR, we first develop highly sensitive assay with plasmid and cell-lines. Next, we compared multiplex assay with duplex assay. Sensitivity was highly correlated (R2 = 0.99) between these assays. Thus, we subsequently analyzed clinical samples (60 advanced lung cancer patients and 17 healthy volunteers). Compared with tumor tissues, multiplex assay using plasma samples demonstrated sensitivity of 66% and specificity of 100%, respectively. Of those, patients who had distant metastasis demonstrated higher sensitivity (81%). Thus, this population may be suitable to further clinical trial.

Research Products

• [Journal Article] Prognostic significance of diabetes mellitus in locally advanced non-small cell lung cancer. (2015)
  • Author(s): Imai H, Kaira K, Mori K, Ono A, Akamatsu H, et al.
  • Journal Title: BMC Cancer Volume: 15 Pages: 989-989
  • DOI: 10.1186/s12885-015-2012-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations. (2015)
  • Author(s): Matsunaga K, Hirano T, Oka A, Tanaka A, Kanai K, Kikuchi T, Hayata A, Akamatsu H, Akamatsu K, Koh Y, Nakanishi M, Minakata Y, Yamamoto N
  • Journal Title: J Allergy Clin Immunol Pract. Volume: 3 Pages: 759-64
  • DOI: 10.1016/j.jaip.2015.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of platinum combination re-challenge therapy and docetaxel monotherapy in non-small cell lung cancer patients previously treated with platinum-based chemoradiotherapy. (2015)
  • Author(s): Imai H, Kaira K, Akamatsu H, et al.
  • Journal Title: Springerplus. Volume: 31:4 Pages: 152-152
  • DOI: 10.1186/s40064-015-0929-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: a case series of eight patients. (2015)
  • Author(s): Miura S, Kaira K, Akamatsu H, et al.
  • Journal Title: Invest New Drugs. Volume: 33(3) Pages: 55-60
  • DOI: 10.1007/s10637-015-0233-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disease flare after gefitinib discontinuation. (2015)
  • Author(s): Akamatsu H, Ono A, Shukuya T
  • Journal Title: Respir Investig. Volume: 53(2) Pages: 68-72
  • DOI: 10.1016/j.resinv.2014.10.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer. (2015)
  • Author(s): Imai H, Mori K, Wakuda K, Ono A, Akamatsu H,
  • Journal Title: Ann Thorac Med. Volume: 10(1) Pages: 61-66
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effect of gefitinib in patients with postoperative recurrent non-small cell lung cancer harboring mutations of the epidermal growth factor receptor. (2015)
  • Author(s): Ko R, Kenmotsu H, Akamatsu H, et al.
  • Journal Title: Int J Clin Oncol. Volume: 20(4) Pages: 668-73
  • DOI: 10.1007/s10147-014-0761-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of actionable mutations in malignant pleural mesothelioma. (2015)
  • Author(s): Takehito Shukuya
  • Journal Title: Lung Cancer. Volume: 86 Pages: 35-40
  • DOI: 10.1016/j.lungcan.2014.08.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disease flare after gefitinib discontinuation. (2015)
  • Author(s): Akamatsu H, Ono A, Shukuya T, Tsuya A, Nakamura Y, Kenmotsu H, Naito T, Murakami H, Endo M, Nakajima T, Yamamoto N
  • Journal Title: Respir Investig Volume: 53 Pages: 68-72
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of platinum combination re-challenge therapy and docetaxel monotherapy in non-small cell lung cancer patients previously treated with platinum-based chemoradiotherapy. (2015)
  • Author(s): Imai H, Kaira K, Mori K, Ono A, Akamatsu H, Taira T, Yoshino R, Kenmotsu H, Saitoh J, Harada H, Naito T, Murakami H, Tomizawa Y, Matsuura M, Saito R, Nakajima T, Yamada M, Takahashi T.
  • Journal Title: Springerplus Volume: 4 Pages: 152-152
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: a case series of eight patients. (2015)
  • Author(s): Miura S, Kaira K, Kaira R, Akamatsu H, Ono A, Shukuya T, Tsuya A, Nakamura Y, Kenmotsu H, Naito T, Murakami H, Takahashi T, Endo M, Yamamoto N.
  • Journal Title: Invest New Drugs. Volume: epub ahead of print
  • Peer Reviewed / Open Access
• [Journal Article] Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer. (2015)
  • Author(s): Imai H, Mori K, Wakuda K, Ono A, Akamatsu H, Shukuya T, Taira T, Kenmotsu H, Naito T, Kaira K, Murakami H, Endo M, Nakajima T, Yamamoto N, Takahashi T.
  • Journal Title: Ann Thorac Med. Volume: 10 Pages: 61-65
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. (2015)
  • Author(s): Kimura M, Naito T, Kenmotsu H, Taira T, Wakuda K, Oyakawa T, Hisamatsu Y, Tokito T, Imai H, Akamatsu H, Ono A, Kaira K, Murakami H, Endo M, Mori K, Takahashi T, Yamamoto N.
  • Journal Title: Support Care Cancer Volume: 23
  • Peer Reviewed / Open Access
• [Journal Article] Multiplexed molecular profiling of lung cancer using pleural effusion (2014)
  • Author(s): Akamatsu H, Koh Y, Kenmotsu H, Naito T, Serizawa M, Kimura M, Mori K, Imai H, Ono A, Shukuya T, Taira T, Murakami H, Ohde Y, Endo M, Nakajima T, Takahashi T, Yamamoto N
  • Journal Title: J Thorac Oncol Volume: 9 Pages: 1048-1052
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The effect of gefitinib in patients with postoperative recurrent non-small cell lung cancer harboring mutations of the epidermal growth factor receptor. (2014)
  • Author(s): Ko R, Kenmotsu H, Hisamatsu Y, Akamatsu H, Omori S, Nakashima K, Oyakawa T, Wakuda K, Shukuya T, Ono A, Imai H, Taira T, Naito T, Murakami H, Mori K, Endo M, Ohde Y, Takahashi K, Takahashi T.
  • Journal Title: Int J Clin Oncol Volume: epub ahead of print
  • Peer Reviewed / Open Access
• [Journal Article] Identification of actionable mutations in malignant pleural mesothelioma. (2014)
  • Author(s): Shukuya T, Serizawa M, Watanabe M, Akamatsu H, Abe M, Imai H, Tokito T, Ono A, Taira T, Kenmotsu H, Naito T, Murakami H, Takahashi T, Endo M, Ohde Y, Nakajima T, Yamamoto N, Koh Y.
  • Journal Title: Lung Cancer Volume: 86 Pages: 35-40
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Individual-level data on the relationships of progression-free survival and post-progression survival with overall survival in patients with advanced non-squamous non-small cell lung cancer patients who received second-line chemotherapy. (2014)
  • Author(s): Imai H, Mori K, Ono A, Akamatsu H, Taira T, Kenmotsu H, Naito T, Kaira K, Murakami H, Endo M, Nakajima T, Takahashi T.
  • Journal Title: Med Oncol Volume: 31 Pages: 88-88
  • Peer Reviewed / Open Access
• [Journal Article] Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline. (2014)
  • Author(s): Matsunaga K, Ichikawa T, Oka A, Morishita Y, Kanai K, Hiramatsu M, Akamatsu H, Kawabata H, Kikuchi T, Akamatsu K, Hirano T, Kou Y, Nakanishi M, Minakata Y, Yamamoto N.
  • Journal Title: Respir Med Volume: 108 Pages: 976-982
  • Peer Reviewed / Open Access
• [Journal Article] Toxicity and efficacy of chemotherapy for non-small cell lung cancer with cavitary lesions. (2014)
  • Author(s): Tokito T, Shukuya T, Akamatsu H, Ono A, Taira T, Kenmotsu H, Naito T, Murakami H, Takahashi T, Endo M, Mori K, Yamamoto N.
  • Journal Title: Respir Investig Volume: 52
  • Peer Reviewed / Open Access
• [Journal Article] Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: a prospective, single-institute study. (2014)
  • Author(s): Serizawa M, Koh Y, Kenmotsu H, Isaka M, Murakami H, Akamatsu H, Mori K, Abe M, Hayashi I, Taira T, Maniwa T, Takahashi T, Endo M, Nakajima T, Ohde Y, Yamamoto N.
  • Journal Title: Cancer Volume: 15 Pages: 1471-81
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients. (2014)
  • Author(s): Shukuya T, Takahashi T, Imai H, Tokito T, Ono A, Akamatsu H, Taira T, Kenmotsu H, Naito T, Murakami H, Endo M, Yamamoto N.
  • Journal Title: Respir Investig Volume: 52 Pages: 101-106
  • Peer Reviewed / Open Access
• [Presentation] Establishment of novel multiplexed assay to detect EGFR mutations using ultra-sensitive digital PCR (2015)
  • Author(s): 赤松弘朗、洪泰浩、山本信之ら
  • Organizer: ESMO Asia 2015
  • Place of Presentation: Suntec, Singapore
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] 胸部原発悪性腫瘍における個別化医療の現状と今後の展望について (2015)
  • Author(s): 洪泰浩
  • Organizer: 第 74 回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] Liquid biopsies: noninvasive longitudinal monitoring of lung cancer. (2015)
  • Author(s): 洪泰浩
  • Organizer: 第 13 回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2015-07-16
  • Invited
• [Presentation] Early Phase Trials Using Liquid Biopsy. (2015)
  • Author(s): 赤松弘朗
  • Organizer: 4th Japan Taiwan Oncology Phase Ⅰ Trial Conference
  • Place of Presentation: NTUH International Convention Center, Taipei, Taiwan
  • Year and Date: 2015-04-26
  • Int'l Joint Research / Invited
• [Presentation] Ongoing early phase trials using liquid biopsy (2015)
  • Author(s): Hiroaki Akamatsu
  • Organizer: The 4th Japan-Taiwan Oncology Phase I Trial Conference
  • Place of Presentation: International Conference Center of National Taiwan University Hospital
  • Year and Date: 2015-04-26
  • Invited
• [Presentation] Establishment of multiplexed ultra-sensitive detection of epidermal growth factor receptor mutations using picodroplet digital PCR (2015)
  • Author(s): Hiroaki Akamatsu, Yasuhiro Koh, Masaru Watanabe, Takashi Kikuchi, Masanori Nakanishi, Kazuto Matsunaga, Nobuyuki Yamamoto.
  • Organizer: American Association of Cancer Research Annual Meeting 2015
  • Place of Presentation: Pennsylvania Convention Center
  • Year and Date: 2015-04-23
• [Presentation] Establishment of multiplexed ultra-sensitive detection of epidermal growth factor receptor mutations using picodroplet digital PCR. (2015)
  • Author(s): 赤松弘朗、洪泰浩、山本信之ら
  • Organizer: American Association for Cancer Research Annual Meeting 2015
  • Place of Presentation: Pennsylvania convention center, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Droplet Digital PCR を用いた EGFR 遺伝子変異のマルチプレックス検出 (2014)
  • Author(s): 渡辺 勝、洪 泰浩、赤松 弘朗、菊池 崇史、松永 和人、山本 信之
  • Organizer: 日本肺癌学会総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-11-15
• [Presentation] Significance ofconsolidation chemotherapyin unresectable, locally advanced non-small cell lung cancer. (2014)
  • Author(s): Hiroaki Akamatsu
  • Organizer: 日本臨床腫瘍学会総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-07-17
  • Invited
• [Book] 呼吸器疾患診療最新ガイドライン (2014)
  • Author(s): 菊池崇史, 赤松弘朗, 山本信之
  • Publisher: 総合医学社
• [Book] がん薬物療法の作用機序 殺細胞性抗悪性腫瘍薬 白金製剤･アルキル化薬･抗がん性抗生物質 (2014)
  • Author(s): 赤松弘朗, 山本信之
  • Publisher: 日本臨床社
• [Book] Ⅲ期非小細胞肺癌の化学放射線療法. (2014)
  • Author(s): 赤松弘朗, 山本信之
  • Publisher: へるす出版
• [Book] EBMの手法による肺癌診療ガイドライン2014年版 (2014)
  • Author(s): 赤松弘朗, 山本信之
  • Publisher: 金原出版
• [Book] 現在進行中の大規模無作為化比較試験 (2014)
  • Author(s): 赤松弘朗, 山本信之
  • Publisher: 南山堂
• [Book] 腫瘍病理鑑別診断アトラス 肺癌 (2014)
  • Author(s): 赤松弘朗, 山本信之
  • Publisher: 文光堂