What is the functionality and nonfunctionality of endocrine tumors?

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21604
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Kyushu University
• Principal Investigator: Ogawa Yoshihiro 九州大学, 医学研究院, 教授 (70291424)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 副腎皮質腫瘍 / 機能性 / 非機能性 / ステロイドミクス解析 / ゲノム解析 / 機械学習

Outline of Final Research Achievements

In this study, we conducted multi-omics analysis with adrenal specimens from patients diagnosed with aldosterone-producing tumors (APA), cortisol-producing tumors (CPA), or nonfunctioning adrenocortical tumors. In tissue steroidomics analysis, we found a significant elevation of cortisol in APA relative to bona fide nonfunctioning tumors, albeit at a lower level relative to CPA. Genomics analysis detected several somatic mutations in a group of genes associated with activation of PKA, an important pathway in cortisol biosynthesis, in CPA, but not in APA, suggesting a different mechanism of cortisol synthesis between APA and CPA. Clustering analysis using machine learning classified adrenocortical tumors into multiple clusters based on the steroidomics data. This study provides clues to elucidate the molecular mechanisms underlying adrenocortical hormones in adrenal tumors, thus helping understand their functionality and non-functionality.

Free Research Field

内科学、内分泌代謝学、糖尿病学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、従来の判定基準による非機能性副腎皮質腫瘍が「脱・非機能性（＝機能性化）」され、機械学習による臨床検体の網羅的解析と臨床情報の統合により、新たな副腎腫瘍学の創成されると思われる。機能性あるいは非機能性副腎皮質腫瘍のホルモン産生能と腫瘍内の細胞レベルの不均一性に関する解析により、「内分泌腫瘍の機能性・非機能性とは何か？」という根本的な問題を見直すことができ、内分泌腫瘍の機能性腫瘍の再分類・再定義につながることが期待される。本研究の波及効果として、ホルモン産生能の有無が問われる他の内分泌腫瘍の機能性・非機能性の再定義・再分類により内分泌腫瘍学にパラダイムシフトをもたらしうる。