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Detailed analysis on SOX9 expression in skin adnexal tumors

Research Project

Project/Area Number 20K16186
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionJikei University School of Medicine (2022)
National Cancer Center Japan (2020-2021)

Principal Investigator

Nishimura Yuuki  東京慈恵会医科大学, 医学部, 助教 (80870055)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords皮膚付属器腫瘍 / SOX9 / 機械学習 / 全エクソーム解析 / skin adnexal tumor / SOX9 / immunohistochemistry / computational pathology / machine learning / whole exome squence / 腫瘍内不均一性
Outline of Research at the Start

皮膚付属器腫瘍は稀な腫瘍であるが、種類が非常に多く、その診断は形態上の微妙な差異からなされることもあり診断に苦慮することも多い。その上、現在のところこれらの鑑別に有用な分子マーカーは見つかっていない。その原因の一つには、付属器腫瘍について十分に分子生物学的な解析が行われていないことが挙げられる。我々は毛芽に発現するSOX9に着目し、その付属器腫瘍における発現や機能を解析することで、皮膚付属器腫瘍の病理診断の基準を確立し、治療につなげていくことを目指している。

Outline of Final Research Achievements

We have demonstrated the importance of the transcription factor SOX9 in the differentiation and diagnosis of adnexal skin tumors by immunostaining and detailed analysis of its distribution and intensity. Although cutaneous adnexal tumors are often difficult to diagnose due to their morphological and phenotypic diversity, SOX9 was shown to have good sensitivity and specificity in the diagnosis of multiple tumors. Furthermore, morphological complexity = heterogeneity was analyzed for sweat gland carcinomas using SOX9 expression, machine learning and multiregion whole exome sequencing within tumors, and we found that such heterogeneity also exists in genome-level mutations. At the same time, we found significant in somatic mutations and copy number alterations. We believe that our result could contribute to the establishment of therapeutic strategies in adnexal carcinomas, for which there is still not even a clue to a cure.

Academic Significance and Societal Importance of the Research Achievements

本研究により皮膚付属器腫瘍、特に希少癌である皮膚付属器癌の診断および生物学について多くが明らかになった。今後の薬物治療に役立つものと考える。また、AI技術を積極的に用いることによって、形態学を定量的に評価し、ひいては遺伝情報の腫瘍内不均一性の予測を行い得ることを示すことができたと考えている。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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