Development of a universal tumor marker to diagnose the whole solid cancers

• Project/Area Number: 17K19893
• Research Category: Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: Gunma University
• Principal Investigator: Kuwano Hiroyuki 群馬大学, 大学院医学系研究科, 教授 (90186560)
• Co-Investigator(Kenkyū-buntansha): 茂木 晃 群馬大学, 大学院医学系研究科, 准教授 (10323362) ; 藤井 孝明 群馬大学, 大学院医学系研究科, 准教授 (40507331) ; 横堀 武彦 群馬大学, 大学院医学系研究科, 寄附講座等教員 (60420098) ; 宮崎 達也 群馬大学, 医学部附属病院, 講師 (70372349) ; 原 圭吾 群馬大学, 医学部附属病院, 助教 (60826270)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: PLS3 / T-plastin / 腫瘍マーカー / 血清マーカー / 固形がん / 循環癌細胞 / 固形癌 / がんスクリーニング / Plastin3 / 肺癌 / 消化管癌

Outline of Final Research Achievements

Several tumor markers are used to evaluate the tumor progression and efficacy of anti-cancer drugs in several solid tumors. The purpose of this study was to establish the Universal Tumor Marker to diagnose the whole solid cancers. Therefore, we focused on the T-plastin (PLS3) which has been reported do to be expressed in whole solid tissues and cancers but not in hematopoietic cells and blood. In this study, we clarified that the expression of PLS3 in serum samples from cancer patients was evaluable using the ELISA method which is commonly used in the clinic now. The expression levels in serum of cancer patients was higher than that of healthy volunteers; suggesting the consistency of our PLS3 hypothesis as a candidate of Universal Tumor Marker. The evaluation of PLS3 in serum samples is expected to be a useful cancer screening tool in the clinic.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的な意義として、これまでPCRで検出されていた血液中PLS3発現が実臨床で頻用されているELISA法で検出可能であることを明らかにした点が挙げられる。さらにPLS3発現は健常者と比較して癌患者で有意に発現亢進しており、この知見は本研究の仮説と一致していた。社会実装の視点ではPLS3は既存の腫瘍マーカーを凌駕する新規Universal Tumor Markerの候補として期待される。

Research Products

• [Journal Article] Genetic and Immunohistochemical Studies Investigating the Histogenesis of Neuroendocrine and Carcinomatous Components of Combined Neuroendocrine Carcinoma (2019)
  • Author(s): Iijima Misaki、Yokobori Takehiko、Mogi Akira、Shimizu Kimihiro、Yajima Toshiki、Kosaka Takayuki、Ohtaki Yoichi、Obayashi Kai、Nakazawa Seshiru、Gombodorj Navchaa、Tsukagoshi Mariko、Shirabe Ken、Kuwano Hiroyuki
  • Journal Title: Annals of Surgical Oncology Volume: Mar
  • DOI: 10.1245/s10434-019-07268-0
  • Peer Reviewed
• [Journal Article] Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer (2019)
  • Author(s): Handa Tadashi、Katayama Ayaka、Yokobori Takehiko、Yamane Arito、Fujii Takaaki、Obayashi Sayaka、Kurozumi Sasagu、Kawabata-Iwakawa Reika、Gombodorj Navchaa、Nishiyama Masahiko、Asao Takayuki、Shirabe Ken、Kuwano Hiroyuki、Oyama Tetsunari
  • Journal Title: International Journal of Oncology Volume: Mar;54(3) Pages: 833-844
  • DOI: 10.3892/ijo.2019.4675
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plastin3 is associated with epithelial?mesenchymal transition and poor prognosis in gastric cancer (2019)
  • Author(s): Kurashige J, Yokobori T, Mima K, Sawada G, Takahashi Y, Ueo H, Takano Y, Matsumura T, Uchi R, Eguchi H, Sudo T, Sugimachi K, Mori M, Baba H, Mimori K.
  • Journal Title: Oncology Letters Volume: 17(2) Pages: 2393-2399
  • DOI: 10.3892/ol.2018.9819
  • Peer Reviewed / Open Access
• [Journal Article] High stromal transforming growth factor β-induced expression is a novel marker of progression and poor prognosis in gastric cancer (2018)
  • Author(s): Suzuki Masaki、Yokobori Takehiko、Gombodorj Navchaa、Yashiro Masakazu、Turtoi Andrei、Handa Tadashi、Ogata Kyoichi、Oyama Tetsunari、Shirabe Ken、Kuwano Hiroyuki
  • Journal Title: Journal of Surgical Oncology Volume: 118 Pages: 966-974
  • DOI: 10.1002/jso.25217
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma (2018)
  • Author(s): Kumakura Yuji、Yokobori Takehiko、Yoshida Tomonori、Hara Keigo、Sakai Makoto、Sohda Makoto、Miyazaki Tatsuya、Yokoo Hideaki、Handa Tadashi、Oyama Tetsunari、Yorifuji Hiroshi、Kuwano Hiroyuki
  • Journal Title: Annals of Surgical Oncology Volume: 25 Pages: 1221-1228
  • DOI: 10.1245/s10434-018-6390-0
  • Peer Reviewed / Open Access
• [Journal Article] High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab (2018)
  • Author(s): Bao H、Bai T、Takata K、Yokobori T、Ohnaga T、Hisada T、Maeno T、Bao P、Yoshida T、Kumakura Y、Honjo H、Sakai M、Sohda M、Fukuchi M、Altan B、Handa T、Ide M、Miyazaki T、Ogata K、Oyama T、Shimizu K、Mogi A、Asao T、Shirabe K、Kuwano H、Kaira K
  • Journal Title: Oncology Letters Volume: 15 Pages: 3061-3067
  • DOI: 10.3892/ol.2017.7671
  • Peer Reviewed / Open Access
• [Journal Article] High STMN1 Expression Is Associated with Tumor Differentiation and Metastasis in Clinical Patients with Pancreatic Cancer. (2018)
  • Author(s): Suzuki K, Watanabe A, Araki K, Yokobori T, Harimoto N, Gantumur D, Hagiwara K, Yamanaka T, Ishii N, Tsukagoshi M, Igarashi T, Kubo N, Gombodorj N, Nishiyama M, Hosouchi Y, Kuwano H, Shirabe K.
  • Journal Title: Anticancer Research Volume: 38(2) Pages: 939-944
  • Peer Reviewed
• [Journal Article] High STMN1 Expression Is Associated with Tumor Differentiation and Metastasis in Clinical Patients with Pancreatic Cancer (2018)
  • Author(s): Suzuki K, Watanabe A, Araki K, Yokobori T, Harimoto N, Gantumur D, Hagiwara K, Yamanaka T, Ishii N, Tsukagoshi M, Igarashi T, Kubo N, Gombodorj N, Nishiyama M, Hosouchi Y, Kuwano H, Shirabe K.
  • Journal Title: Anticancer Research Volume: 38 Pages: 939-944
  • DOI: 10.21873/anticanres.12307
  • Peer Reviewed / Int'l Joint Research