Development of the therapeutic targets for salivary gland carcinoma using virtual pathology and antibody-based proteomics

• Project/Area Number: 25670868
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: National Cancer Center Japan
• Principal Investigator: HONDA Kazufumi 独立行政法人国立がん研究センター, 研究所, ユニット長 (10260936)
• Co-Investigator(Kenkyū-buntansha): MORI Taisuke 国立研究開発法人国立がん研究センター中央病院, 病理科 (00296708) ; 野村 武史 東京歯科大学, オーラルメディシン・口腔外科学講座, 教授 (60328268)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 唾液腺がん / 組織マイクロアレイ / プロテオミクス / 仮想病理画像 / 定量抗体プロテオミクス / 抗体基盤プロテオミクス / 画像解析ソフトウエア / 国際研究者交流 / 国際情報交換

Outline of Final Research Achievements

To identify the biomarker for decision of therapeutic strategy in salivary gland carcinoma, we made tissue microarray of the salivary gland carcinoma, and searched it by antibody-based proteomics. We identified overexpression of actiin-4 (ACTN4) that is associated with cancer metastasis in salivary gland carcinoma. To confirm the gene amplification of ACTN4, we investigated the copy number of ACTN4 by FISH analysis. FISH (fluorescence in situ hybridization) revealed that overall survival time of patients with gene amplification of ACTN4 was significantly shorter than it of patients with normal copy number. The multivariate Cox regression analysis revealed that gene amplification of ACTN4 remained as an independent prognostic factor. The gene amplification of ACTN4 is a potential prognostic biomarker for salivary gland carcinoma.

Research Products

• [Journal Article] The Alternatively Spliced Actinin-4 Variant as a Prognostic Marker for Metastasis in Small-cell Lung Cancer. (2015)
  • Author(s): Okamoto N, Suzuki H, Kawahara K, Honda K, Miura N, Hirashima T, Tamiya M, Morishita N, Shiroyama T, Tanaka A, Tani E, Hamaguchi M, Kitani M, Yamada T, and Kawase
  • Journal Title: Anticancer Res Volume: 35(3) Pages: 1663-7
  • Peer Reviewed
• [Journal Article] ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer. (2015)
  • Author(s): Watanabe T, Ueno H, Watabe Y, Hiraoka N, Morizane C, Itami J, Okusaka T, Miura N, Kakizaki T , Kakuya T, Kamita M, Tsuchida A, Nagakawa Y, Wilber H, Yamada T and Honda K
  • Journal Title: Br J Cancer Volume: Feb 17;112(4) Issue: 4 Pages: 704-13
  • DOI: 10.1038/bjc.2014.623
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] プロテオーム解析による膵癌診断方法の開発 (2015)
  • Author(s): 三 浦奈美、紙田正博、本田一文、山田哲司
  • Journal Title: 膵癌治療 up-to-date 2015 Volume: 2015 Pages: 91-98
• [Journal Article] Histological growth pattern of and alpha-actinin-4 expression in thyroid cancer. (2014)
  • Author(s): Tanaka N, Yamashita T, Yamamoto S, Matsunobu T, Tsuda H, Honda K, Yamada T, Tamai S, Shiotani A.
  • Journal Title: Anticancer Res. Volume: Jun;34(6) Pages: 3157-63
  • Peer Reviewed
• [Journal Article] Alternative mammalian target of rapamycin (mTOR) signal activation in sorafenib-resistant hepatocellular carcinoma cells revealed by array-based pathway profiling. (2014)
  • Author(s): Masuda M, Chen WY, Miyanaga A, Nakamura Y, Kawasaki K, Sakuma T, Ono M, Chen CL, Honda K, Yamada T
  • Journal Title: Mol Cell Proteomics. Volume: Jun;13(6) Issue: 6 Pages: 1429-38
  • DOI: 10.1074/mcp.m113.033845
  • Peer Reviewed / Open Access
• [Journal Article] Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome. (2014)
  • Author(s): Arai E, Sakamoto H, Ichikawa H, Totsuka H, Chiku S, Gotoh M, Mori T, Nakatani T, Ohnami S, Nakagawa T, Fujimoto H, Wang L, Aburatani H, Yoshida T, Kanai Y.
  • Journal Title: Int J Cancer. Volume: On line Issue: 3 Pages: 613-22
  • DOI: 10.1002/cam4.214
  • Peer Reviewed / Open Access
• [Journal Article] 臨床材料を用いたアレイ基盤プロテオミクスを用いた創薬標的・バイオマーカーの開発, (2014)
  • Author(s): 小林信， 山田哲司， 本田一文
  • Journal Title: 医学のあゆみ Volume: 251 (10), Pages: 980-983
• [Journal Article] 肺がんの予後予測と遺伝子シグナチャー (特集 がん分子診断のパラダイムシフト) (2014)
  • Author(s): 山田哲司， 野呂林太郎， 本田一文
  • Journal Title: 最新医学 Volume: 69 (12) Pages: 2512-2519
  • NAID: 40020289928
• [Journal Article] Narrow-band imaging system with magnifying endoscopy for early oral cancer. (2014)
  • Author(s): Shibahara T, Yamamoto N, Yakushiji T, Nomura T, Sekine R, Muramatsu, K, Ohata, H.
  • Journal Title: The -Bulletin of Tokyo Dental College. Volume: 55(2): Pages: 87-94
  • NAID: 130004868700
  • Peer Reviewed
• [Journal Article] Molecular biological change in oral cancer, summary of our researches (2014)
  • Author(s): Yamamoto N, Onda T, Sugahara K, Nomura T, Shibahara, T.
  • Journal Title: Japanese Dental Science Review Volume: 51(1): Issue: 1 Pages: 25-33
  • DOI: 10.1016/j.jdsr.2014.09.003
  • NAID: 50009645831
  • Peer Reviewed
• [Journal Article] 口腔扁平上皮癌周囲に広がる上皮性異形成に対する切除範囲の決定法 (2014)
  • Author(s): 野村武史, 柴原孝彦.
  • Journal Title: 歯科学報 Volume: 114(6) Pages: 195-202
  • Peer Reviewed
• [Journal Article] Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy (2014)
  • Author(s): Murakami N, Mori T, Yoshimoto S, Ito Y, Kobayashi K, Ken H, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Sumi M, Itami J.
  • Journal Title: Laryngoscope. Volume: Nov;124(11): Issue: 11 Pages: 431-436
  • DOI: 10.1002/lary.24839
  • Peer Reviewed
• [Journal Article] Utility of PAX8 mouse monoclonal antibody in the diagnosis of thyroid, thymic, pleural, and lung tumors: a comparison with polyclonal PAX8 antibody. (2014)
  • Author(s): Toriyama A, Mori T, Sekine S, Yoshida A, Hino O, Tsuta K.
  • Journal Title: Histopathology Volume: On line Issue: 4 Pages: 465-72
  • DOI: 10.1111/his.12405
  • Peer Reviewed
• [Journal Article] Secondary osteosarcoma developing 10 years after chemoradiotherapy for non-small-cell lung cancer. (2014)
  • Author(s): Yagishita S, Horinouchi H, Yorozu T, Kitazono S, Mizugaki H, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Mori T, Tsuta K, Sumi M, Tamura T.
  • Journal Title: Jpn J Clin Oncol Volume: Feb;44(2): Issue: 2 Pages: 191-4
  • DOI: 10.1093/jjco/hyt192
  • Peer Reviewed
• [Journal Article] Alternative mTOR signal activation in sorafenib-resistant hepatocellular carcinoma cells revealed by array-based pathway profiling. (2014)
  • Author(s): Masuda M, Chen WY, Miyanaga A, Nakamura Y, Kawasaki K, Sakuma T, Ono M, Chen CL, Honda K, Yamada T.
  • Journal Title: Mol Cell Proteomics Volume: In press
  • Peer Reviewed
• [Journal Article] MicroRNA expression and functional profiles of osteosarcoma. (2014)
  • Author(s): Kobayashi E, Satow R, Ono M, Masuda M, Honda K, Sakuma T, Kawai A, Morioka H, Toyama Y, Yamada T.
  • Journal Title: Oncology Volume: 86(2): Issue: 2 Pages: 94-103
  • DOI: 10.1159/000357408
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical actinin-4 expression in infiltrating gliomas: association with WHO grade and differentiation. (2014)
  • Author(s): Fukushima S, Yoshida A, Honda K, Maeshima AM, Narita Y, Yamada T, Shibui S, Tsuda H.
  • Journal Title: Brain Tumor Pathol. Volume: Jan;31(1): Issue: 1 Pages: 11-6
  • DOI: 10.1007/s10014-013-0139-z
  • Peer Reviewed
• [Journal Article] Basic study of soft tissue augmentation by adipose-inductive biomaterial (2014)
  • Author(s): Yazawa M, Mori T, Kishi K
  • Journal Title: Journal of Biomedical Materials Research: Part B - Applied Biomaterials. Volume: In press
  • Peer Reviewed
• [Journal Article] Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome. (2014)
  • Author(s): Arai E, Sakamoto H, Ichikawa H, Totsuka H, Chiku S, Gotoh M, Mori T, Nakatani T, Ohnami S, Nakagawa T, Fujimoto H, Wang L, Aburatani H, Yoshida T, Kanai Y.
  • Journal Title: Int J Cancer Volume: 135 Issue: 6 Pages: 1330-1342
  • DOI: 10.1002/ijc.28768
  • Peer Reviewed / Open Access
• [Journal Article] Histopathological characteristics of hypervascular cholangiocellular carcinoma as an early stage of cholangiocellular carcinoma. (2014)
  • Author(s): Sato Y, Ojima H, Onaya H, Mori T, Hiraoka N, Kishi Y, Nara S, Esaki M, Shimada
  • Journal Title: Hepatol Res. Volume: Sept 6 Issue: 11 Pages: 1119-1129
  • DOI: 10.1111/hepr.12236
  • Peer Reviewed
• [Journal Article] Junctional Rab13-binding protein (JRAB) re requires cell spreading via filamins. (2013)
  • Author(s): Sakane, A
  • Journal Title: Genes Cells Volume: 18 Issue: 9 Pages: 810-822
  • DOI: 10.1111/gtc.12078
  • Peer Reviewed
• [Journal Article] Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy. (2013)
  • Author(s): Makuuchi Y, Honda K, Osaka Y, Kato K, Kojima T, Daiko H, Igaki H, Ito Y, Hoshino S, Tachibana S, Watanabe T, Furuta K, Sekine S, Umaki T, Watabe Y, Miura N, Ono M, Tsuchida A, Yamada T.
  • Journal Title: Cancer Sci. Volume: Aug;104(8): Issue: 8 Pages: 1045-51
  • DOI: 10.1111/cas.12187
  • Peer Reviewed
• [Journal Article] Sox10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: A clue to the histogenesis and diagnosis (2013)
  • Author(s): Ohtomo R, Mori T, Shibata S, Tsuta K, Maeshima M, Akazawa C, Honda K, Yamada T, Yoshimoto S, Asai M, Okano H, Kanai Y, Tsuda H
  • Journal Title: Modern Pathology Volume: Aug;26(8): Issue: 8 Pages: 1041-50
  • DOI: 10.1038/modpathol.2013.54
  • Peer Reviewed
• [Journal Article] Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification. (2013)
  • Author(s): Noro R1, Honda K, Tsuta K, Ishii G, Maeshima AM, Miura N, Furuta K, Shibata T, Tsuda H, Ochiai A, Sakuma T, Nishijima N, Gemma A, Asamura H, Nagai K, Yamada T.
  • Journal Title: Ann Oncol Volume: Oct;24(10): Issue: 10 Pages: 2594-600
  • DOI: 10.1093/annonc/mdt293
  • Peer Reviewed
• [Journal Article] Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis. (2013)
  • Author(s): Yamazaki H, Mori T, Yazawa M, Maeshima AM, Matsumoto F, Yoshimoto S, Ota Y, Kaneko A, Tsuda H, Kanai Y.
  • Journal Title: Lab Invest. Volume: Dec;93(12): Issue: 12 Pages: 1331-8
  • DOI: 10.1038/labinvest.2013.120
  • Peer Reviewed
• [Journal Article] Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. (2013)
  • Author(s): Nishikawa G, Sekine S, Ogawa R, Matsubara A, Mori T, Taniguchi H, Kushima R, Hiraoka N, Tsuta K, Tsuda H, Kanai Y.
  • Journal Title: Br J Cancer. Volume: Mar 5;108(4): Issue: 4 Pages: 951-8
  • DOI: 10.1038/bjc.2013.47
  • Peer Reviewed
• [Journal Article] Bisphosphonate-related osteonecrosis of jaw (BRONJ) in Japanese population: a case series of 13 patients at our clinic. (2013)
  • Author(s): Nomura T
  • Journal Title: Bull Tokyo Dent Coll. Volume: 54 Pages: 117-125
  • NAID: 130004868681
  • Peer Reviewed
• [Presentation] 「口腔がん治療の均てん化・標準化」特別講演 「がん個別化医療・早期診断バイオマーカーの開発と実用化」 (2015)
  • Author(s): 本田一文
  • Organizer: 文部科学省 がんプロフェッショナル養成基盤推進プラン－高度がん医療開発を先導する専門家の養成－4大学合同事業：慶應義塾大学・東海大学・東京歯科大学・信州大学 公開講座
  • Place of Presentation: 新宿NSビル東京都
  • Year and Date: 2015-02-08
  • Invited
• [Presentation] 口腔癌の性質を反映する分子診断 (2015)
  • Author(s): 森 泰昌
  • Organizer: 文部科学省 がんプロフェッショナル養成基盤推進プラン－高度がん医療開発を先導する専門家の養成－4大学合同事業：慶應義塾大学・東海大学・東京歯科大学・信州大学 公開講座
  • Place of Presentation: 新宿NSビル東京都
  • Year and Date: 2015-02-08
  • Invited
• [Presentation] 「シスプラチン耐性克服に向けた創薬を目指して-進行卵巣がんのシスプラチン耐性腫瘍に対する創薬-」 (2015)
  • Author(s): 本田一文
  • Organizer: 日本医療研究開発機構設立準備委員会、医薬基盤研、理化学研究所、産業総合研究所主催【オールジャパンの創薬支援－創薬立国日本に向けて】創薬支援ネットワーク・シンポジウム
  • Place of Presentation: グランフロント大阪 ナレッジシアター 大阪市
  • Year and Date: 2015-01-16
  • Invited
• [Presentation] トランスオミクスワークショップ 「プロテオミクス総括」 (2014)
  • Author(s): 本田一文
  • Organizer: 第1回トランスオミクス研究会
  • Place of Presentation: 東北メディカルメガバンク 仙台市
  • Year and Date: 2014-12-06
  • Invited
• [Presentation] 頭頸部における稀少がんの病理 (2014)
  • Author(s): 森 泰昌
  • Organizer: 第59回 日本口腔外科学会総会 シンポジウム
  • Place of Presentation: 幕張国際会議場 千葉市
  • Year and Date: 2014-10-19
  • Invited
• [Presentation] 唾液腺がん組織マイクロアレイを用いた予後予測バイオマーカーの同定 (2014)
  • Author(s): 本田一文
  • Organizer: 日本口腔外科学会・日本口腔病理学会・日本歯科放射線学会、口腔3学会シンポジウム
  • Place of Presentation: 幕張国際会議場 千葉市
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Possible Detection of Early-Stage Pancreatic Cancer by Measuring Plasma Apolipoprotein-AII isoforms (2014)
  • Author(s): Kazufumi Honda1, Michimoto Kobayashi2, Giman Jung2, Tesshi Yamada1
  • Organizer: Scientific Workshop, National Cancer Institute (NCI), Early Detection Research Network (EDRN),
  • Place of Presentation: Hyatt Regency Bethesda ML, USA.
  • Year and Date: 2014-10-10
• [Presentation] 膵臓がんの早期発見;膵がん検診の効率化を目指した血液バイオマーカーの実用化- (2014)
  • Author(s): 本田一文
  • Organizer: パープルリボン医療セミナージャパン東京2014
  • Place of Presentation: 星陵会館
  • Year and Date: 2014-10-05
  • Invited
• [Presentation] 「がん個別化医療バイオマーカーの開発と実用化」 (2014)
  • Author(s): 本田一文
  • Organizer: 第62回重粒子医科学センター研究交流会
  • Place of Presentation: 独立行政法人 放射線医学研究所 千葉市
  • Year and Date: 2014-09-04
  • Invited
• [Presentation] がん個別化医療選択のためのバイオマーカー開発と実用化 (2014)
  • Author(s): 本田一文
  • Organizer: 27回青森呼吸器研究会 特別講演
  • Place of Presentation: ホテル青森 青森市
  • Year and Date: 2014-08-30
  • Invited
• [Presentation] アレイ技術・抗体基盤・質量分析基盤プロテオミクスの融合-がんバイオマーカー探索と検証に向けて- (2014)
  • Author(s): 本田一文
  • Organizer: 日本プロテオーム学会2014年大会 シンポジウム
  • Place of Presentation: つくば国際会議場 つくば市
  • Year and Date: 2014-07-18
  • Invited
• [Presentation] Gene amplification of ACTN4 is a predictor of cancer metastasis. (2014)
  • Author(s): Kazufumi Honda, and Tesshi Yamada.
  • Organizer: 15th International Biennial Congress of the Metastasis Research Society
  • Place of Presentation: German Cancer Research Center. Dkfz. Heidelberg Germany.
  • Year and Date: 2014-06-30
• [Presentation] Actinin-4 expression is a predictive biomarker for late metastasis of cervical lymph nodes in early-stage tongue cancer (2013)
  • Author(s): Yukio Watabe1,2, Kazufumi Honda1, Taisuke Mori3, Nami Miura1, Takeshi Nomura2, Takahiko Shibahara2, and Tesshi Yamada1
  • Organizer: 21st international conference on oral and maxillofacial surgery-
  • Place of Presentation: Barcelona Spein
• [Presentation] Actinin-4 is a predictive biomarker for late metastasis of stage I-II tongue cancer
  • Author(s): Kazufumi Honda, Yukio Watabe, Takeshi Nomura, Takahiko Shibahara, Wilber Huang, Wei-Yu Chen, Chi-Long Chen Tesshi Yamada
  • Organizer: 2014 Annual Congress of ROC Association of Oral and Maxillofacial Surgeons, Taiwan, March 8th 2014.
  • Place of Presentation: Tainan Taiwan
• [Presentation] Rapid biomarker validation by high-density plasma protein array
  • Author(s): Kazufumi Honda, Masaya Ono, Masahiro Kamita, Tomohiko Kakizaki, Tesshi Yamada
  • Organizer: 3rd Global Reverse Phase Protein Microarray Workshop
  • Place of Presentation: Kobe Japan
  • Invited
• [Presentation] 難治がん早期診断血液バイオマーカーの開発と多施設共同研究による迅速検証法の構築
  • Author(s): 本田一文、山田哲司
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] シスタチオニンγリアーゼ（CSE)の阻害は、シスプラチンの効果を増強する
  • Author(s): 本田一文
  • Organizer: 第1回 がんと代謝研究会
  • Place of Presentation: 鶴岡
  • Invited
• [Presentation] The mechanism of resistance for chemotherapy in advanced stage of ovarian cancer
  • Author(s): Kazufumi Honda1, Sohei Yamamoto2, Hitoshi Tsuda2,3, Nami Miura1, Mitsuyo Omura4, Yoshihiro Izumi5, Masashi Takano6, Takahiro Kasamatsu7, Masaru Yoshida5, Makoto Suematsu4 & Tesshi Yamada1
  • Organizer: 第８６回日本生化学学会大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 個別化医療バイオマーカーの同定と実用化
  • Author(s): 本田一文
  • Organizer: 第58回日本口腔外科学会総会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 肺がんの相別化バイオマーカーについて
  • Author(s): 本田一文
  • Organizer: The 4th meeting Society of Basic and Translational Research in Oncology and Respirology
  • Place of Presentation: 東京
  • Invited
• [Presentation] がん個別化医療選択のためのバイオマーカー開発と実用化
  • Author(s): 本田一文
  • Organizer: 国際癌治療増感研究会 次世代がん治療推進専門家養成プラン シンポジウム
  • Place of Presentation: 東京
  • Invited