Development of predictive biomarkers for preoerative therapy responses in patients with rectal cancer

• Project/Area Number: 16K10545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Ohki Shinji 福島県立医科大学, 医学部, 准教授 (20381361)
• Co-Investigator(Kenkyū-buntansha): 岡山 洋和 福島県立医科大学, 医学部, 講師 (20583397) ; 門馬 智之 福島県立医科大学, 医学部, 講師 (20622335) ; 齋藤 元伸 福島県立医科大学, 医学部, 講師 (90611749)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 直腸癌 / 術前治療 / バイオマーカー

Outline of Final Research Achievements

Neoadjuvant chemoradiotherapy (CRT) followed by surgical mesorectal excision is widely used to reduce local recurrence rates in patients with locally advanced rectal cancer. However, tumor response to CRT varies substantially among patients, ranging from resistance to complete pathological regression. This study aimed to develop transcriptional assays for predicting neoadjuvant CRT responses using pre-therapeutic biopsy specimens based on high-throughput gene expression technologies. Three microarray datasets were utilized as discovery cohorts to screen for genes that can be predictive of poor response to CRT. We identified a gene set that can pre-therapeutically discriminate non-responders from responders. We attempted to evaluate the predictive performance of our gene set as well as multi-gene or single-gene expression-based signatures previously reported using four independent validation cohorts.

Academic Significance and Societal Importance of the Research Achievements

個々の直腸癌患者に最適な治療を選択することで、直腸癌の再発率の低下やＱＯＬの改善に寄与すると言える。直腸癌の手術前に放射線化学療法が広く行われているが、その感受性は患者によりさまざまである。本研究では術前放射線化学療法への抵抗性を事前に予測するためのバイオマーカーの作成を意図しており、本研究で得られた知見が、今後の直腸癌の個別的治療につながる一助となることを期待するものである。

Research Products

• [Journal Article] Prognostic role of FUT8 expression in relation to p53 status in stage II and III colorectal cancer (2018)
  • Author(s): Noda Masaru、Okayama Hirokazu、Kofunato Yasuhide、Chida Shun、Saito Katsuharu、Tada Takeshi、Ashizawa Mai、Nakajima Takahiro、Aoto Keita、Kikuchi Tomohiro、Sakamoto Wataru、Endo Hisahito、Fujita Shotaro、Saito Motonobu、Momma Tomoyuki、Ohki Shinji、Kono Koji
  • Journal Title: PLOS ONE Volume: 13 Issue: 7 Pages: 315-315
  • DOI: 10.1371/journal.pone.0200315
  • Peer Reviewed / Open Access
• [Journal Article] Glycosyltransferase Gene Expression Identifies a Poor Prognostic Colorectal Cancer Subtype Associated with Mismatch Repair Deficiency and Incomplete Glycan Synthesis (2018)
  • Author(s): Noda Masaru、Okayama Hirokazu、Tachibana Kazunoshin、Sakamoto Wataru、Saito Katsuharu、Thar Min Aung Kyi、Ashizawa Mai、Nakajima Takahiro、Aoto Keita、Momma Tomoyuki、Katakura Kyoko、Ohki Shinji、Kono Koji
  • Journal Title: Clinical Cancer Research Volume: 24 Issue: 18 Pages: 4468-4481
  • DOI: 10.1158/1078-0432.ccr-17-3533
  • Peer Reviewed / Open Access
• [Journal Article] Upregulated solute carrier family 37 member 1 in colorectal cancer is associated with poor patient outcome and metastasis (2018)
  • Author(s): Kikuchi Daiki、Saito Motonobu、Saito Katsuharu、Watanabe Yohei、Matsumoto Yoshiko、Kanke Yasuyuki、Onozawa Hisashi、Hayase Suguru、Sakamoto Wataru、Ishigame Teruhide、Momma Tomoyuki、Ohki Shinji、Takenoshita Seiichi
  • Journal Title: Oncology Letters Volume: 15 Pages: 2065-2072
  • DOI: 10.3892/ol.2017.7559
  • Peer Reviewed
• [Journal Article] Enhanced expression of KIF4A in colorectal cancer is associated with lymph node metastasis (2018)
  • Author(s): Matsumoto Yoshiko、Saito Motonobu、Saito Katsuharu、Kanke Yasuyuki、Watanabe Yohei、Onozawa Hisashi、Hayase Suguru、Sakamoto Wataru、Ishigame Teruhide、Momma Tomoyuki、Kumamoto Kensuke、Ohki Shinji、Takenoshita Seiichi
  • Journal Title: Oncology Letters Volume: 15 Pages: 2188-2194
  • DOI: 10.3892/ol.2017.7555
  • Peer Reviewed
• [Journal Article] Upregulated HOXA9 expression is associated with lymph node metastasis in colorectal cancer (2017)
  • Author(s): Watanabe Yohei、Saito Motonobu、Saito Katsuharu、Matsumoto Yoshiko、Kanke Yasuyuki、Onozawa Hisashi、Hayase Suguru、Sakamoto Wataru、Ishigame Teruhide、Momma Tomoyuki、Ohki Shinji、Takenoshita Seiichi
  • Journal Title: Oncology Letters Volume: 15 Pages: 2756-2762
  • DOI: 10.3892/ol.2017.7650
  • Peer Reviewed
• [Journal Article] L?type amino acid transporter 1 expression is upregulated and associated with cellular proliferation in colorectal cancer (2017)
  • Author(s): Hayase Suguru、Kumamoto Kensuke、Saito Katsuharu、Kofunato Yasuhide、Sato Yu、Okayama Hirokazu、Miyamoto Kotaro、Ohki Shinji、Takenoshita Seiichi
  • Journal Title: Oncology Letters Volume: 14 Pages: 7410-7416
  • DOI: 10.3892/ol.2017.7148
  • Peer Reviewed
• [Journal Article] Annexin A1 is involved in resistance to 5-FU in colon cancer cells (2017)
  • Author(s): Onozawa Hisashi、Saito Motonobu、Saito Katsuharu、Kanke Yasuyuki、Watanabe Yohei、Hayase Suguru、Sakamoto Wataru、Ishigame Teruhide、Momma Tomoyuki、Ohki Shinji、Takenoshita Seiichi
  • Journal Title: Oncology Reports Volume: 37 Issue: 1 Pages: 235-240
  • DOI: 10.3892/or.2016.5234
  • Peer Reviewed
• [Presentation] ハイリスクstageⅡ大腸癌におけるinflammatory-based markerの意義と個別化治療戦略. (2018)
  • Author(s): 大木進司,岡山洋和,芦澤舞,菊池智宏,坂本渉,藤田正太郎,遠藤久仁,齋藤元伸,門馬智之,佐瀬善一郎,河野浩二.
  • Organizer: 第14回日本消化管学会総会学術集会
• [Presentation] Targeting the tumor microenvironment in dMMR/MSI-H colorectal cancer. (2018)
  • Author(s): Okayama H, Ashizawa M, Kikuchi T, Sakamoto W, Fujita S, Endo H, Saito M, Momma T, Ohki S, Kono K.
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] 糖鎖酵素遺伝子によるステージIII大腸癌の予後バイオマーカー (2018)
  • Author(s): 岡山洋和,野田勝,立花和之進,坂本渉,芦澤舞,中島隆宏,青砥慶太,門馬智之,大木進司,河野浩二.
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] 胃癌・大腸癌におけるANXA1遺伝子の役割 (2018)
  • Author(s): 齋藤元伸,小野澤寿志,作山美郷,芦澤舞,菊池智宏,岡山洋和,遠藤久仁,藤田正太郎,坂本渉,佐瀬善一郎,門馬智之,大木進司,河野浩二
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 大腸癌新鮮標本における腫瘍随伴マクロファージの解析 (2018)
  • Author(s): 菊池智宏,三村耕作,岡山洋和,坂本渉,遠藤久仁,藤田正太郎,齋藤元伸,門馬智之,大木進司,河野浩二
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] 免疫チェックポイント阻害療法時代のリンチ症候群スクリーニングの位置づけ (2018)
  • Author(s): 大木進司,氏家大輔,門馬智之,芦澤舞,岡山洋和,藤田正太郎,遠藤久仁,坂本渉,菊池智宏,齋藤元伸,河野浩二
  • Organizer: 第73回日本大腸肛門病学会学術集会
• [Presentation] 家族性大腸腺腫症に対する術式の検討 (2018)
  • Author(s): 門馬智之,片方雅紀,佐藤孝洋,菊池智宏,岡山洋和,坂本渉,藤田正太郎,遠藤久仁,齋藤元伸,佐瀬善一郎,大木進司,河野浩二
  • Organizer: 第73回日本大腸肛門病学会学術集会
• [Presentation] 術前放射線治療を施行した進行下部直腸癌に対する側方リンパ節郭清の意義 (2017)
  • Author(s): 大木 進司,岡山 洋和,藤田 正太郎,坂本 渉,遠藤 久仁,齋藤 元伸,門馬 智之,円谷 彰,丸橋 繁,河野 浩二
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] stage II/III下部直腸癌に対する術前放射線治療の功罪と個別化に関する検討 (2016)
  • Author(s): 大木 進司, 隈元 謙介, 早瀬 傑, 藤田 正太郎, 門馬 智之, 岡山 洋和, 高和 正, 河野 浩二, 竹之下 誠一
  • Organizer: 第116回日本消化器外科学会定期学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-14