Detection of specific markes for accutete mesothelioma diagnosis based on comprehensive genome expression analysis

• Project/Area Number: 17K08742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hiroshima University
• Principal Investigator: Takeshima Yukio 広島大学, 医系科学研究科(医), 教授 (70236462)
• Co-Investigator(Kenkyū-buntansha): AMATYA VISHWA・J 広島大学, 医系科学研究科(医), 講師 (90403625) ; 櫛谷 桂 広島大学, 医系科学研究科(医), 助教 (00508179)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: mesothelioma / adenocarcinoma / antibody / differential diagnosis / immunohistochemistry / 中皮腫 / 遺伝子発現解析 / マイクロアレー / 免疫組織化学的染色 / 網羅的遺伝子発現解析 / 病理診断 / 免疫組織化学的診断 / 新規マーカー

Outline of Final Research Achievements

By using whole genone expression anaysis, we found gene showing differentially between epithelioid mesothelioma and lung adenocarcinoma, and staind mesothelioma and adenocarcinoma tissues, and clarified sensitivity and specificity. As the result, in mesothelioma, DAB2, Intelectin-1, SOX6, PRG4, Annexin-8 gene and protein expression in mesothelioma, and MUC4, MUC21 in adenocarcinoma were significantly higher. These novel markers have higher sensititity and specificity than convential differential markers. Therefore, these novel markes could be used for differential diagnosis between mesothelioma and lung adenocarcinoma.

Academic Significance and Societal Importance of the Research Achievements

中皮腫の病理診断は各種抗体を用いて行うが、現在用いられている抗体のみでは鑑別診断が困難な場合がある。そこで、網羅的遺伝子発現解析を基本にして、鑑別診断に有用なマーカーを見いだした。その結果、中皮腫ではDAB2, Intelectin-1, SOX6, PRG4, Annexin-8が、 肺腺癌ではMUC4, MUC21が発現が有意に高いことが明らかとなり、これら新規マーカーが、中皮腫と肺腺癌の鑑別診断に利用可能であることが示された。

Research Products

• [Int'l Joint Research] South Valley University, Qena, Egypt(Egypt)
• [Journal Article] 胸膜中皮腫 (2019)
  • Author(s): 武島幸男、櫛谷 桂、Amatha V. Jeet
  • Journal Title: 病理と臨床 Volume: 37 Pages: 1073-1081
• [Journal Article] Mucin 21 is a novel, negative immunohistochemical marker for epithelioid mesothelioma for its differentiation from lung adenocarcinoma (2019)
  • Author(s): Kai Yuichiro、Amatya Vishwa J、Kushitani Kei、Kambara Takahiro、Suzuki Rui、Tsutani Yasuhiro、Miyata Yoshihiro、Okada Morihito、Takeshima Yukio
  • Journal Title: Histopathology Volume: 74 Issue: 4 Pages: 545-554
  • DOI: 10.1111/his.13775
  • Peer Reviewed / Open Access
• [Journal Article] MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung (2018)
  • Author(s): Mawas AS, Amatya VJ, Kushitani K, Kai Y, Miyata Y, Okada M, Takeshima Y.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1
  • DOI: 10.1038/s41598-017-18545-x
  • NAID: 120006796545
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid mesothelioma from lung adenocarcinoma (2018)
  • Author(s): Amatya VJ, Kushitani K, Kai Y, Suzuki R, Miyata Y, Okada M, Takeshima Y.
  • Journal Title: Modern Pathology Volume: 31 Issue: 5 Pages: 809-815
  • DOI: 10.1038/modpathol.2017.190
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for its Differentiation From Pulmonary Adenocarcinoma. (2017)
  • Author(s): Kuraoka M, Amatya VJ, Kushitani K, Mawas AS, Miyata Y, Okada M, Kishimoto T, Inai K, Nishisaka T, Sueda T, Takeshima Y.
  • Journal Title: American Journal of Surgical Patholology Volume: 41 Issue: 8 Pages: 1045-1052
  • DOI: 10.1097/pas.0000000000000852
  • Peer Reviewed
• [Presentation] 上皮型中皮腫と肺腺癌の鑑別診断における新規マーカーSOX6の有用性 (2019)
  • Author(s): 神原 貴大,AmatyaVishwaJeet,鈴木 瑠偉,甲斐佑一郎,櫛谷 桂,武島 幸男
  • Organizer: 第108回日本病理学会総会
• [Presentation] 上皮型中皮腫と非小細胞性肺癌の鑑別診断におけるPRG4、Annexin-8免疫組織化学的染色の有用性 (2019)
  • Author(s): 櫛谷 桂, 甲斐佑一郎, Amatya Vishwa Jeet，鈴木瑠偉, 神原貴大、武島幸男
  • Organizer: 第108回日本病理学会総会
• [Presentation] PRG4とMUC21は上皮性中皮腫と肺腺癌の新規鑑別マーカーである (2018)
  • Author(s): 甲斐佑一郎，Amatya V.J.，櫛谷 桂，宮田義浩，岡田守人，鈴木瑠偉，武島幸男
  • Organizer: 第107回日本病理学会総会
• [Presentation] 上皮型中皮腫と肺腺癌の鑑別診断におけるPRG4免疫組織化学的染色の有用性 (2018)
  • Author(s): 櫛谷 桂，甲斐佑一郎，Amatya V.J.，鈴木瑠偉，神原貴大，武島幸男
  • Organizer: 第25回石綿・中皮腫研究会
• [Presentation] Diagnostic utility of MUC4 expression to differentiate epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma (2017)
  • Author(s): Amatya V.J., Mawas A.S., Kushitani K., Kai Y., Miyata Y., Okada M. and Takeshima Y.
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Identification of DAB2 and Intelection-1 as novel positive immunohistochemical markers of epithelioid mesothelioma (2017)
  • Author(s): Kuraoka M., Amatya V.J., Kushitani K., Mawas A.S., Miyata Y., Okada M., Kishimoto T., Inai K., Nishisaka T., Sueda T. and Takeshima Y
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma and lung squamous cell carcinoma (2017)
  • Author(s): Kushitani K., Amatya V.J., (Okada Y., Katayama Y., Mawas A.S., Miyata Y., Okada M., Inai K., Kishimoto T. and Takeshima Y.
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research