Identification of endometrial adenocarcinoma biomarkers and therapeutic target candidates by proteomic analysis

• Project/Area Number: 15K10735
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nippon Medical School
• Principal Investigator: Peng Wei-Xia 日本医科大学, 医学部, 講師 (00535700)
• Co-Investigator(Kenkyū-buntansha): 内藤 善哉 日本医科大学, 大学院医学研究科, 大学院教授 (20237184) ; 和田 龍一 日本医科大学, 医学部, 准教授 (20260408)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 子宮内膜癌 / 予後 / プロテオーム解析 / 免疫組織化学 / 類内膜癌 / 網羅的な蛋白質解析 / 脱分化 / 類内膜腺癌 / バイオマーカー

Outline of Final Research Achievements

To identify potential prognostic biomarkers in endometrioid carcinoma (EC), we performed proteomic analysis and immunohistochemistry (IHC). Firstly, we revealed the total protein expression in 3 grades ECs respectively, and compared the protein expression profiles between grades. Then we validated the protein expression using IHC and compared the protein expression patterns with clinical factors. Compare to G1 EC, differentially expressed proteins in G3 was 56 types. Among them, we focused the Filamin A. In IHC study, G3 ECs showed significantly higher expression of Filamin A than G1 and G2 ECs. Furthermore, strong expression of Filamin A tended to be associated with cancer frequent recurrence and lymphovascular invasion.The current analysis revealed the significant association of high expression Filamin A and unfavorable prognostic factors of ECs, suggesting that Filamin A may play a critical role in EC invasiveness and prognosis.

Academic Significance and Societal Importance of the Research Achievements

今回の検討では、Filamin Aの発現は子宮類内膜癌の脱分化に関与する可能性が示唆され、予後不良のバイオマーカーとして有用の可能性が考えられる。

Research Products

• [Journal Article] Downregulation of protein disulfide-isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma (2019)
  • Author(s): Kondo R, Ishino K, Wada R, Takata H, Peng WX, Kudo M, Kure S, Kaneya Y, Taniai N, Yoshida H, Naito Z
  • Journal Title: International Journal of Oncology Volume: 54 Pages: 1409-1421
  • DOI: 10.3892/ijo.2019.4710
  • Peer Reviewed
• [Journal Article] 2-Deoxy-D-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells (2018)
  • Author(s): Ishino K, Kudo M, Peng WX, Kure S, Kawahara K, Teduka K, Kawamoto Y, Kitamura T, Fujii T, Yamamoto T, Wada R, Naito Z
  • Journal Title: Biochem Biophys Res Comm Volume: 501 Issue: 3 Pages: 668-673
  • DOI: 10.1016/j.bbrc.2018.05.041
  • Peer Reviewed / Open Access
• [Journal Article] 平滑筋分化を伴った低悪性度子宮内膜間質肉腫の1例 (2017)
  • Author(s): 呉 壮香, 和田 龍一, 彭 為霞, 坂谷 貴司, 内藤 善哉
  • Journal Title: 診断病理 Volume: 34 Pages: 1345-6431
  • Peer Reviewed
• [Journal Article] Identification of aldolase A as a potential diagnostic biomarker for colorectal cancer based on proteomic analysis using formalin-fixed paraffin-embedded tissue. (2016)
  • Author(s): Yamamoto T, Kudo M, Peng WX, Takata H, Takakura H, Teduka K, Fujii T, Mitamura K, Taga A, Uchida E, Naito Z.
  • Journal Title: Tumour Biol Volume: 37 Pages: 13595-13606
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma. (2016)
  • Author(s): Takata H, Kudo M, Yamamoto T, Ueda J, Ishino K, Peng WX, Wada R, Taniai N, Yoshida H, Uchida E, Naito Z.
  • Journal Title: Oncol Lett. Volume: 12 Issue: 1 Pages: 4896-4904
  • DOI: 10.1097/prs.0000000000002900
  • Peer Reviewed / Open Access
• [Journal Article] Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma. (2016)
  • Author(s): Kanzaki A, Kudo M, Ansai S, Peng WX, Ishino K, Yamamoto T, Wada R, Fujii T, Teduka K, Kawahara K, Kawamoto Y, Kitamura T, Kawana S, Saeki H, Naito Z.
  • Journal Title: Int J Oncol Volume: 48 Issue: 3 Pages: 1007-15
  • DOI: 10.3892/ijo.2016.3323
  • Peer Reviewed / Open Access
• [Presentation] 子宮内膜細胞診で発見された原発性卵管癌の1例 (2017)
  • Author(s): Wei-Xia Peng
  • Organizer: 第58回日本臨床細胞学会総会
• [Presentation] A soft tissue tumor with extensive myxoid change in femal genital tract (2016)
  • Author(s): Wei-Xia Peng
  • Organizer: The 20th Japan Taiwan Korea Joint Meeting for Gynecological Pathology
  • Place of Presentation: 韓国・ソウル大学
  • Year and Date: 2016-09-02
  • Int'l Joint Research
• [Presentation] Malignant endometrial polyp: a case report (2015)
  • Author(s): Wei-Xia Peng, Kousuke Ishino, Keisuke Kurose, Mitsuhiro Kudo, Ryuichi Wada, Zenya Naito
  • Organizer: The 39th European Congress of Cytology
  • Place of Presentation: Milano, Italy
  • Year and Date: 2015-09-20
  • Int'l Joint Research
• [Book] カラーイラストで学ぶ 集中講義 病理学 (2016)
  • Author(s): 彭 為霞 (共著）
  • Total Pages: 354
  • Publisher: メジカルビュー社