An integrative multi-omic analysis for biomarker discovery in glioblastoma
Project/Area Number |
19H03774
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
|
Research Institution | Yokohama City University |
Principal Investigator |
KIMURA Yayoi 横浜市立大学, 先端医科学研究センター, 准教授 (80391936)
|
Co-Investigator(Kenkyū-buntansha) |
立石 健祐 横浜市立大学, 附属病院, 助教 (00512055)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
Keywords | プロテオミクス / バイオマーカー探索 / Glioblastoma / GBM / マルチオミクス / 癌 / バイオマーカー / プロテオーム解析 / 脳腫瘍 |
Outline of Research at the Start |
本研究では、独自に樹立した病態再現性の高いヒト由来脳腫瘍細胞株を活用して、マルチオミクス解析から脳腫瘍の表現型を決定するタンパク質を絞り込み、これらを標的とする新たなプロテオーム解析技術 (TatgetDIA法)を確立する。さらに、この解析技術を利用し、患者血清中の脳腫瘍に由来するタンパク質を探索し、患者の病態を正確に把握・分類し、治療方針を決定する、脳腫瘍のための体液診断バイオマーカーの開発を目指す。
|
Outline of Final Research Achievements |
Glioblastoma (GBM) is the most common primary brain tumor with high malignancy and poor prognosis in the patient. Despite various treatment options, GBM frequently exhibits recurrence and infiltrates into normal brain tissue leading to mortality. To discover biomarkers for GBM that characterize the disease states as well as driver oncogene mutations, we performed an integrative multi-omic analysis using ChIp-seq, RNA-seq and proteomic data from human GBM patient-derived cells, which faithfully retained their phenotypic, metabolic, and genetic features. We successfully found candidate molecules as available biomarkers for serodiagnosis and prediction of the temozolomide therapeutic effect in GBM. The present study is expected to contribute to improved outcomes for GBM by enabling accurate diagnosis and appropriate treatment options.
|
Academic Significance and Societal Importance of the Research Achievements |
脳腫瘍は生検が容易でなく、治療方針検討の指標が得難い。この問題を解決するため、MRIなどの画像診断法や血液や脳脊髄液など体液を活用した低侵襲な診断法の確立が強く望まれている。本研究では、頭蓋外より侵襲を伴わずに生体内の腫瘍の状態を評価できるGBMタンパク質を見い出した。これを客観的な診断指標として臨床応用することで、個々の患者に必要な治療のみを行う個別化医療が可能となり、患者らの身体的・精神的負担の軽減、副作用の少ない医療、効果的な治療法の選択による治療成績の向上ならびに医療費の削減が期待できる。
|
Report
(4 results)
Research Products
(69 results)
-
[Journal Article] HSP90 inhibition overcomes resistance to molecular targeted therapy in BRAFV600E mutant high-grade glioma2022
Author(s)
Sasame J, Ikegaya N, Kawazu M, Natsumeda M, Hayashi T, Isoda M, Satomi K, Tomiyama A, Oshima A, Honma H, Miyake Y, Takabayashi K, Nakamura T, Ueno T, Matsushita Y, Iwashita H, Kanemaru Y, Murata H, Ryo A, Terashima K, Yamanaka S, Fujii Y, Mano H, Komori T, Ichimura K, Cahill DP, Wakimoto H, Yamamoto T, Tateishi K.
-
Journal Title
Clin Cancer Res
Volume: 印刷中
Issue: 11
Pages: 2425-2439
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
[Journal Article] IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology.2021
Author(s)
Miyake Y, Fujii K, Nakamaura T, Ikegaya N, Matsushita Y, Gobayashi Y, Iwashita H, Udaka N, Kumagai J, Murata H, Takemoto Y, Yamanaka S, Ichimura K, Tateishi K, Yamamoto T.
-
Journal Title
J Neuropathol Exp Neurol.
Volume: 80
Issue: 3
Pages: 247-253
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Sirtuin activation targets IDH-mutant tumors2021
Author(s)
Miller Julie J、Fink Alexandria、Banagis Jack A、Nagashima Hiroaki、Subramanian Megha、Lee Christine K、Melamed Lisa、Tummala Shilpa S、Tateishi Kensuke、Wakimoto Hiroaki、Cahill Daniel P
-
Journal Title
Neuro-Oncology
Volume: 23
Issue: 1
Pages: 53-62
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Proteomic and phospholipidomic characterization of extracellular vesicles inducing tumor microenvironment in Epstein-Barr virus-associated lymphomas.2021
Author(s)
Ito M, Kudo K, Higuchi H, Otsuka H, Tanaka M, Fukunishi N, Araki T, Takamatsu M, Ino Y, Kimura Y, Kotani A.
-
Journal Title
FASEB J.
Volume: 35
Issue: 4
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Effects of microgravity exposure and fructo-oligosaccharide ingestion on the proteome of soleus and extensor digitorum longus muscles in developing mice2021
Author(s)
Ohira, T., Y. Ino, Y. Kimura, Y. Nakai, A. Kimura, Y. Kurata, H. Kagawa, M. Kimura, K. Egashira, C. Matsuda, Y. Ohira, S. Furukawa, and H. Hirano
-
Journal Title
npj Microgravity
Volume: 7
Issue: 1
Pages: 34-34
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
[Journal Article] Thiel's embalming method with additional intra-cerebral ventricular formalin injection (TEIF) for cadaver training of head and brain surgery.2020
Author(s)
Miyake S, Suenaga J, Miyazaki R, Sasame J, Akimoto T, Tanaka T, Ohtake M, Takase H, Tateishi K, Shimizu N, Murata H, Funakoshi K, Yamamoto T.
-
Journal Title
Anatomical Science International
Volume: N/A
Issue: 4
Pages: 564-570
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] Mitochondrial Fission Mediates Endothelial Inflammation.2020
Author(s)
Forrester SJ, Preston KJ, Cooper HA, Boyer MJ, Escoto KM, Poltronetti AJ, Elliott KJ, Kuroda R, Miyao M, Sesaki H, Akiyama T, Kimura Y, Rizzo V, Scalia R, Eguchi S.
-
Journal Title
Hypertension
Volume: 76
Issue: 1
Pages: 267-276
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] FLCN Alteration Drives Metabolic Reprogramming Towards Nucleotide Synthesis and Cyst Formation in Salivary Gland2020
Author(s)
Isono Y, Furuya M, Kuwahara T, Sano D, Suzuki K, Jikuya R, Mitome T, Otake S, Kawahara T, Ito Y, Muraoka K, Nakaigawa N, Kimura Y, Baba M, Nagahama K, Takahata H, Saito I, Schmidt LS, Linehan WM, Kodama T, Yao M, Oridate N, Hasumi H.
-
Journal Title
Biochem Biophys Res Commun
Volume: 522
Issue: 4
Pages: 931-938
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Proteomic analysis revealed different responses to hypergravity of soleus and extensor digitorum longus muscles in mice2020
Author(s)
Ohira T, Ino Y, Nakai Y, Morita H, Kimura A, Kurata Y, Kagawa H, Kimura M, Egashira K, Moriya S, Hiramatsu K, Kawakita M, Kimura Y, Hirano H
-
Journal Title
Journal of Proteomics
Volume: 217
Pages: 103686-103686
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Novel targets identified by integrated cancer-stromal interactome analysis of pancreatic adenocarcinoma.2020
Author(s)
Hiroshima Y, Kasajima R, Kimura Y, Komura D, Ishikawa S, Ichikawa Y, Bouvet M, Yamamoto N, Oshima T, Morinaga S, Singh SR, Hoffman RM, Endo I, Miyagi Y.
-
Journal Title
Cancer Lett.
Volume: 469
Pages: 217-227
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
[Journal Article] High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-12020
Author(s)
Maezawa Y, Sakamaki K, Oue N, Kimura Y, Hashimoto I, Hara K, Kano K, Aoyama T, Hiroshima Y, Yamada T, Yamamoto N, Ogata T, Ito H, Cho H, Shiozawa M, Yoshikawa T, Morinaga S, Rino Y, Yausi W, Masuda M, Miyagi Y, Oshima T
-
Journal Title
J Cancer Res Clin Oncol
Volume: 146
Issue: 1
Pages: 75-86
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy2020
Author(s)
Kano K, Sakamaki K, Oue N, Kimura Y, Hashimoto I, Hara K, Maezawa Y, Aoyama T, Fujikawa H, Hiroshima Y, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Cho H, Ito H, Shiozawa M, Yukawa N, Yoshikawa T, Morinaga S, Rino Y, Yasui W, Masuda M, Miyagi Y, Oshima T.
-
Journal Title
In vivo
Volume: 34
Issue: 1
Pages: 461-467
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Autologous Transfusion of Blood Aspirated during Suction Decompression in Clipping of Large or Giant Cerebral Aneurysm2019
Author(s)
Ryo Matsuzawa, M.D.*, Hidetoshi Murata, M.D., Ph.D. (equal contribution)*, Mitsuru Sato, M.D., Ryohei Miyazaki, M.D., Takahiro Tanaka, M.D., Nobuyuki Shimizu, M.D., Ph.D., Kensuke Tateishi, M.D., Ph.D., Jun Suenaga, M.D., Ph.D., Tetsuya Yamamoto, M.D., Ph.D.
-
Journal Title
Neurologia medico-chirurgica
Volume: 59
Issue: 9
Pages: 351-356
DOI
NAID
ISSN
0470-8105, 1349-8029
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Genome-wide DNA Methylation Profiling Shows Molecular Heterogeneity of Anaplastic Pleomorphic Xanthoastrocytoma2019
Author(s)
Nakamura T, Fukuoka K, Nakano Y, Yamasaki K, Matsushita Y, Yamashita S, Ikeda J, Udaka N, Tanoshima R, Shiba N, Tateishi K, Yamanaka S, Yamamoto T, Hirato J, Ichimura K.
-
Journal Title
Cancer Sci.
Volume: 110
Issue: 2
Pages: 828-832
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] PI3K/AKT/mTOR pathway alterations promote malignant progression and xenograft formation in oligodendroglial tumors.2019
Author(s)
Tateishi K, Nakamura T, Juratli TA, Williams EA, Matsushita Y, Miyake S, Nishi M, Miller JJ, Ryo A, Yamanaka S, Curry WT, Dias-Santagata D, Yamamoto T, Ichimura K, Batchelor T, Chi AS, Iafrate AJ, Wakimoto H, Cahill DP, et al.
-
Journal Title
Clin Cancer Res.
Volume: 印刷中
Issue: 14
Pages: 4375-4387
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] Clinical significance of KIAA1199 as a novel target for gastric cancer drug therapy2019
Author(s)
Oneyama M, Sakamoto N, Oue N, Kimura Y, Hiroshima Y, Hashimoto I, Hara K, Maezawa Y, Kano K, Aoyama T, Fujikawa H, Yamada T, Tamagawa H, Yamamoto N, Ogata T, Cho H, Ito H, Yukawa N, Shiozawa M, Yoshikawa T, Morinaga S, Rino Y, Masuda M, Miyagi Y, Yasui W, Oshima T
-
Journal Title
Anticancer Res
Volume: 39
Issue: 12
Pages: 6567-6573
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] ヒト由来中枢神経原発悪性リンパ腫細胞株を用いた腫瘍発生進展機構の解明、治療法探求のためのトランスレーショナル研究.2019
Author(s)
立石健祐, 佐々木重嘉, 河津正人, 三宅勇平, 中村大志, 吉井幸恵, 松下裕子, 山中正二, 山本哲哉, 脇本浩明, 永根基雄, 市村幸一.
Organizer
第37回日本脳腫瘍学会学術総会
Related Report
-
-
-
[Presentation] ヒト由来中枢神経原発悪性リンパ腫細胞株を用いた腫瘍発生進展機構の解明、治療法探求のためのトランスレーショナル研究2019
Author(s)
立石健祐, 佐々木重嘉, 河津正人, 三宅勇平, 中村大志, 吉井幸恵, 松下裕子, 山中正二, 山本哲哉, 脇本浩明, 永根基雄, 市村幸一.
Organizer
第20回日本分子脳神経外科学会
Related Report
-
-
-
-