Molecular characterization of carcinoma arising in mature cystic teratoma of the ovary

• Project/Area Number: 18K16760
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Niigata University
• Principal Investigator: Tamura Ryo 新潟大学, 医歯学総合病院, 助教 (70650620)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 卵巣成熟嚢胞性奇形腫 / RNAシーケンス / XCL1 / TP53 / PIK3CA / RMAシーケンス / 抗PD1/PD-L1抗体 / 全エクソンシーケンス / CD8 / PD-L1 / 融合遺伝子 / FGFR3-TACC3 / TACSTD2-OMA1 / UPK3B-PMS2 / 成熟嚢胞性奇形腫悪性転化 / 扁平上皮癌

Outline of Final Research Achievements

In this study, we analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. Next, we identified XCL1 was specifically overexpressed in MCT-SCCs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 expression may be a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.

Academic Significance and Societal Importance of the Research Achievements

これまでに明らかになっていなかった卵巣成熟嚢胞性奇形腫悪性転化の分子生物学的特徴について、統合オミックス解析を用いて明らかにした。特に重要な点として、本疾患の腫瘍XCL1発現が、免疫チェックポイント阻害薬の治療効果を予測するバイオマーカーになる可能性が示唆されたことが挙げられる。本研究は、本疾患における免疫チェックポイント阻害薬の有効性を示唆する重要な結果であり、臨床的意義が大きいと思われる。

Research Products

• [Journal Article] XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary (2020)
  • Author(s): Tamura Ryo、Yoshihara Kosuke、Nakaoka Hirofumi、Yachida Nozomi、Yamaguchi Manako、Suda Kazuaki、Ishiguro Tatsuya、Nishino Koji、Ichikawa Hiroshi、Homma Keiichi、Kikuchi Akira、Ueda Yutaka、Takei Yuji、Fujiwara Hiroyuki、Motoyama Teiichi、Okuda Shujiro、Wakai Toshifumi、Inoue Ituro、Enomoto Takayuki
  • Journal Title: Oncogene Volume: 39 Issue: 17 Pages: 3541-3554
  • DOI: 10.1038/s41388-020-1237-0
  • Peer Reviewed / Open Access
• [Presentation] XCL1 expression as a diagnostic biomarker and a possible biomarker of immune checkpoint inhibitor therapy for squamous cell carcinoma arising from mature cystic teratoma of the ovary (2020)
  • Author(s): Ryo Tamura, Kosuke Yoshihara, Nozomi Yachida, Manako Yamaguchi, Kazuaki Suda, Tatsuya Ishiguro, Koji Nishino, Akira Kikuchi, Yutaka Ueda, Yuji Takei, Hiroyuki Fujiwara and Takayuki Enomoto
  • Organizer: 第72回日本産科婦人科学会学術講演会
• [Presentation] 卵巣成熟嚢胞性奇形腫悪性転化に対するオミックスデータ解析 ～新規治療戦略の構築を目指して～ (2019)
  • Author(s): 田村亮
  • Organizer: 第6回新潟産婦人科シンポジウム