論文

国際誌
2021年8月24日

Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma.

Gynecologic oncology
  • Ryo Tamura
  • Kosuke Yoshihara
  • Koji Matsuo
  • Nozomi Yachida
  • Ai Miyoshi
  • Kotaro Takahashi
  • Kentaro Sugino
  • Manako Yamaguchi
  • Yutaro Mori
  • Kazuaki Suda
  • Tatsuya Ishiguro
  • Shujiro Okuda
  • Teiichi Motoyama
  • Hirofumi Nakaoka
  • Akira Kikuchi
  • Yutaka Ueda
  • Ituro Inoue
  • Takayuki Enomoto
  • 全て表示

163
2
開始ページ
327
終了ページ
333
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ygyno.2021.08.009

BACKGROUND: Although ovarian clear cell carcinoma (CCC) is associated with high incidence of thromboembolism, the clinicopathological and biological significance of hypercoagulable status in CCC remains unclear. MATERIALS AND METHODS: We retrospectively analyzed pretreatment D-dimer levels, thromboembolic status, and clinical outcome of 125 CCCs in the discovery set and 143 CCCs in two other independent validation sets. Next, we performed RNA sequencing of 93 CCCs and compared coagulation-related gene profiles with 2492 pan-cancer data. We investigated differences in molecular characteristics of CCC subclasses based on coagulation status. RESULTS: In the discovery dataset, D-dimer elevation above the normal range was significantly associated with shorter progression-free and overall survival, irrespective to thromboembolic status. Multivariate analysis identified D-dimer elevation and clinical stage as an independent prognostic factors. We confirmed the prognostic significance of D-dimer elevation in the validation sets. Tissue factor and IL6, which are considered key elements of cancer-induced hypercoagulation, were highly expressed in CCC than in other cancers regardless of D-dimer level. Higher activity of various oncogenic pathways was observed in CCC with compared to without D-dimer elevation. Moreover, hierarchical cluster analysis divided 57 CCCs with D-dimer elevation into immunologically hot and cold tumor subtypes. Hot tumors were characterized by enrichment of T-cell inflamed phenotype, inflammation, the epithelial-mesenchymal transition, and high serum levels of CRP, and cold tumors by enrichment of cell cycle and MYC pathways. CONCLUSIONS: CCC represents hypercoagulable disease and elevate D-dimer is a prognostic factor for decreased survival in CCC. D-dimer high CCC has distinct molecular characteristics into the inflammatory-driven pathway (hot tumor) and the immune-suppressive pathway (cold tumor). Treatment implication of our proposed molecular classification merits further investigation.

リンク情報
DOI
https://doi.org/10.1016/j.ygyno.2021.08.009
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34452748
ID情報
  • DOI : 10.1016/j.ygyno.2021.08.009
  • PubMed ID : 34452748

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