Clinicopathological characteristics and genomic profiles of RGS1 positive lymphoid neoplasms

• Project/Area Number: 18K15100
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tokai University
• Principal Investigator: CARRERAS Joaquim 東海大学, 医学部, 講師 (90637191)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: RGS1 / リンパ腫 / 血液がん / びまん性大細胞型B細胞リンパ腫 / 濾胞性リンパ腫 / 免疫染色 / 遺伝子発現分析 / 腫瘍免疫微環境 / DLBCL / lymphoma / immune microenvironment / immune checkpoint / neoplasia / clinicopathological / genome profiling

Outline of Final Research Achievements

(1) RGS1 is a protein necessary for the structure of lymphoid tissues.(2) This study focuses on the RGS1 expression in hematological neoplasia, with focus on the analysis of RGS1 in the Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), MALT Lymphoma, other small B-cell lymphomas and Hodgkin Lymphoma. The immunohistochemical expression of RGS1 was variable. Immunohistochemical expression of RGS1 was associated with the prognosis of the patients. For example, high RGS1 expression associated with poor prognosis in DLBCL and FL. In addition, a correlation between RGS1 and tumor immune microenvironment was created.(3) The gene expression analysis of Diffuse Large B-cell Lymphoma gene was also performed and the relationship of RGS1 with other relevant clinicopathological markers was assessed.(4) The gene expression analysis was also analyzed by Artificial Intelligence.(5) Immunostaining was also analyzed by Artificial Intelligence.

Academic Significance and Societal Importance of the Research Achievements

RGS1は免疫システムの正しい機能に必要なタンパク質です。 RGS1は免疫系のいくつかの腫瘍であると分析しました。 RGS1がいくつかの腫瘍で可変的に発現されることを見出した。RGS1の発現がいくつかの腫瘍の患者の予後と相関していることを発見しました。 タンパク質発現レベルと遺伝子発現の分析を行いました。 分析は従来型であり、人工知能でもありました。 患者の予後と相関するため、このマーカーは重要です。 リンパ系腫瘍の診断時に、このマーカーをマーカーの診断パネルに含めることができます。 このマーカーは薬物でターゲットにできます。

Research Products

• [Int'l Joint Research] Pathology, Lausanne University/Prof. Laurence de Leval(スイス)
• [Int'l Joint Research] Pathology, Clinic Hosp, UB, IDIBAPS, CEK/Prof. Elias Campo/Dr. Patricia Perez(スペイン)
• [Int'l Joint Research] Spanish Cancer Research Institute/Dr. Alejo Efeyan/Dr. Giovanna Roncador(スペイン)
• [Int'l Joint Research] Clinical Sciences Depart., Sharjah Univ./Dr. Rifat Hamoudi(アラブ首長国連邦)
• [Int'l Joint Research] Cancer Research UK Barts Centre/Prof. Jude Fitzgibbon(英国)
• [Journal Article] Artificial Intelligence Analysis of Gene Expression Data Predicted the Prognosis of Patients with Diffuse Large B-Cell Lymphoma. (2020)
  • Author(s): Carreras J, Hamoudi R, Nakamura N.
  • Journal Title: The Tokai Journal of Experimental and Clinical Medicine Volume: 45 Pages: 37-38
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Methotrexate-associated lymphoproliferative disorder demonstrating composite lymphoma of EBV-negative diffuse large B-cell lymphoma and EBV-positive mucocutaneous ulcer (2020)
  • Author(s): Moriya Keiichi、Kikuti Yara Yukie、Carreras Joaquim、Kondo Yusuke、Shiraiwa Sawako、Nakamura Naoya
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 60 Issue: 1 Pages: 11-16
  • DOI: 10.3960/jslrt.19038
  • NAID: 130007821369
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma (2020)
  • Author(s): Kawashima M, Carreras J, Higuchi H, Kotaki R, Hoshina T, Okuyama K, Suzuki N, Kakizaki M, Miyatake Y, Ando K, Nakayama M, Umezu S, Horie R, Higuchi Y, Katagiri K, Goyama S, Kitamura T, Chamoto K, Yano S,Nakamura N, and A Kotani
  • Journal Title: Leukemia Volume: - Issue: 9 Pages: 2405-2417
  • DOI: 10.1038/s41375-020-0737-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PD-L1 is induced on hepatocyte surface via CKLF-like MARVEL transmembrane domain-containing protein 6 upregulation by the anti-HBV drug Entecavir (2020)
  • Author(s): Yamamoto Yuichiro、Kakizaki Masatoshi、Shimizu Takayuki、Carreras Joaquim、Chiba Tetsuhiro、Chamoto Kenji、Kagawa Tatehiro、Aoki Taku、Nakamura Naoya、Ando Kiyoshi、Kotani Ai
  • Journal Title: International Immunology Volume: - Issue: 8 Pages: 519-531
  • DOI: 10.1093/intimm/dxaa018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oncogenic Rag GTPase signalling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR (2019)
  • Author(s): Ortega-Molina Ana、Deleyto-Seldas Nerea、Carreras Joaquim、Sanz Alba、Lebrero-Fernandez Cristina、Menendez Camino、et al.
  • Journal Title: Nature Metabolism Volume: 1 Issue: 8 Pages: 775-789
  • DOI: 10.1038/s42255-019-0098-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expression of IL‐34 correlates with macrophage infiltration and prognosis of diffuse large B‐cell lymphoma (2019)
  • Author(s): Noyori Osamu、Komohara Yoshihiro、Nasser Hesham、Hiyoshi Masateru、Ma Chaoya、Pan Cheng、Carreras Joaquim、Nakamura Naoya、Sato Ai、Ando Kiyoshi、Okuno Yutaka、Nosaka Kisato、Matsuoka Masao、Suzu Shinya
  • Journal Title: Clinical & Translational Immunology Volume: 8 Issue: 8
  • DOI: 10.1002/cti2.1074
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation (2019)
  • Author(s): Carreras Joaquim、Lopez-Guillermo Armando、Kikuti Yara Yukie、Itoh Johbu、Masashi Miyaoka、Ikoma Haruka、Tomita Sakura、Hiraiwa Shinichiro、Hamoudi Rifat、Rosenwald Andreas、Leich Ellen、Martinez Antonio、Roncador Giovanna、Villamor Neus、Colomo Lluis、Perez Patricia、Tsuji Noriko M、Campo Elias、Nakamura Naoya
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 59 Issue: 1 Pages: 1-16
  • DOI: 10.3960/jslrt.19003
  • NAID: 130007626107
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity. (2019)
  • Author(s): S.Tsuda, J. Carreras, Y. kikuchi, H.Nakae, M. Dekiden, J. Imai, K. Tsuruya, J. Nakamura, Y. Tsukune, T. Uchida, M. Matsushima, G. Roncador, T. Suzuki, N. Nakamura, T. Mine.
  • Journal Title: Pathology International. Volume: - Issue: 5 Pages: 1-12
  • DOI: 10.1111/pin.12794
  • Peer Reviewed
• [Journal Article] Genomic Profile and Pathologic Features of Diffuse Large B-Cell Lymphoma Subtype of Methotrexate-associated Lymphoproliferative Disorder in Rheumatoid Arthritis Patients (2018)
  • Author(s): Carreras J, Yukie Kikuti Y, Miyaoka M, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Shiraiwa S, Ando K, Sato S, Suzuki Y, Miura I, Roncador G, Nakamura N
  • Journal Title: American Journal of Surgical Pathology Volume: 42 Issue: 7 Pages: 936-950
  • DOI: 10.1097/pas.0000000000001071
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Classical Hodgkin lymphoma-type and monomorphic-type post-transplant lymphoproliferative disorder following liver transplantation: a case report. (2018)
  • Author(s): Kumata H, Nakanishi C, Murakami K, Miyagi S, Fukuhara N, Carreras J, Nakamura N, Ichinohasama R, Unno M, Kamei T, Sasano H.
  • Journal Title: Surg Case Rep. Volume: 4 Issue: 1 Pages: 72-72
  • DOI: 10.1186/s40792-018-0480-x
  • Peer Reviewed
• [Journal Article] Monomorphic epitheliotropic intestinal T-cell lymphoma with T-cell receptor (TCR) of silent phenotype shows rearrangement of TCRβ or TCRγ gene. (2018)
  • Author(s): Sakura Tomita
  • Journal Title: Pathology International Volume: 69(2) Issue: 2 Pages: 117-118
  • DOI: 10.1111/pin.12748
  • Peer Reviewed / Open Access
• [Presentation] 精巣びまん性大細胞型B細胞リンパ腫 (2020)
  • Author(s): Carreras Joaquim
  • Organizer: 第5回リンパ腫分子病態研究会 東京シンポジウム
• [Presentation] MYC gene cluster amplification Diffuse large B-cell lymphomaの３例 (2019)
  • Author(s): 宮岡雅，菊池イアーラ幸江，カレーラスジュアキム，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] Heterogeneity of genomic alteration in pediatric follicular lymphoma (2019)
  • Author(s): 中澤温子，Joaquim Carreras，菊池イアーラ幸江，岩淵英人，小林良二，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] ２か所の生検部位からそれぞれEBV陽性mucocutaneous ulcerとEBV陰性DLBCLと診断されたMethotrexate関連リンパ増殖性疾患の一例 (2019)
  • Author(s): 守屋慶一，近藤裕介，宮岡雅，Carreras Joaquim，菊池イアーラ幸江，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] Monomorphic epitheliotropic intestinal T-cell lymphomaにおける遺伝子変異解析 (2019)
  • Author(s): 冨田さくら，Joaquim Carreras，菊池イアーラ幸江，Laurence deLeval，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] GCB （nCounter） Non-GCB （Hans classifier） DLBCLは予後不良である (2019)
  • Author(s): 平岩真一郎，Carreras Joaquim，菊池イアーラ幸江，宮岡雅，生駒悠，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] Genomic Profile and Pathologic Features of Diffuse Large B-Cell Lymphoma Subtypeof Methotrexate-associated Lymphoproliferative Disorder （DLBCL MTX-LPD） in Rheumatoid Arthritis （RA） Patients (2019)
  • Author(s): Carreras Joaquim，菊池イアーラ幸江，宮岡雅，平岩信一郎，冨田さくら，生駒悠，BeaSilvia，RoncadorGiovanna，鈴木康夫，佐藤慎二，加留部謙之輔，三浦偉久男，安藤潔，Campo Elias，中村直哉
  • Organizer: 59回日本リンパ網内系学会総会
• [Presentation] DECIPHERING THE CONTRIBUTION OF MACROPHAGES TO FOLLICULAR LYMPHOMA PATHOGENESIS: NEW INSIGHTS INTO THERAPY (2019)
  • Author(s): P. Perez Galan, Carreras Joaquim, et al.
  • Organizer: 15-ICML -15th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA
  • Int'l Joint Research
• [Presentation] FFPEを用いたMYC遺伝子再構成DLBCLの統合的遺伝子解析 (2019)
  • Author(s): 宮岡 雅、 菊池 イアーラ幸江、カレーラス ジュアキム、中村 直哉。
  • Organizer: 第108回日本病理学会総会
• [Presentation] DLBCL subtype of MTX-LPDのターゲット遺伝子シーケンス解析 (2019)
  • Author(s): カレーラス ジュアキム、菊池 イアーラ幸江、宮岡 雅、平岩 真一郎、生駒 悠、冨田 さくら、ロンカドル ギオバンナ、カンポ エリアス、中村 直哉。
  • Organizer: 第108回日本病理学会総会
• [Presentation] 唾液腺導管癌におけるBDNF、NT-4の発現の意義 (2019)
  • Author(s): 平林 健一, Carreras Joaquim, 槻木 恵一, 中村
  • Organizer: 第108回日本病理学会総会
• [Presentation] DLBCL subtype of MTX-LPDの臨床病理学的特徴とゲノム解析 (2018)
  • Author(s): Joaquim Carreras, Yara Yukie Kikuti, Miyaoka Masashi, Hiraiwa Shinichiro, Ikoma Haruka, Tomita Sakura, Roncador Giovanna, Naoya Nakamura
  • Organizer: 第107回日本病理学会総会
• [Presentation] Genome profile and clinicopathological characteristics of RGS1-positive Diffuse Large B-Cell Lymphoma (RGS1+DLBCL) (2018)
  • Author(s): Carreras Joaquim (カレーラス ジュアキム), 菊池 イアーラ幸江, 宮岡 雅, 加留部 謙之輔, 菰原 義弘, Bea Silvia, Hamoudi Rifat, Perez Patricia, Roncador Giovanna, Campo Elias, 中村 直哉
  • Organizer: 第58回日本リンパ網内系学会総会
• [Remarks] Research activities of Joaquim Carreras Esteban
  • URL: http://carreras.med.u-tokai.ac.jp/