AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 8; pp. 9843 - 9848
• Main Authors: Matsumoto, Minoru, Ohmura, Takuya, Hanibuchi, Yuto, Ichimura‐Shimizu, Mayuko, Saijo, Yasuyo, Ogawa, Hirohisa, Miyazawa, Ryuichiro, Morimoto, Junko, Tsuneyama, Koichi, Matsumoto, Mitsuru, Oya, Takeshi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2023; John Wiley and Sons Inc; Wiley
• Subjects: AIRE; AIRE Protein; Antibodies; Archives & records; Bioinformatics; Brief Communication; Cancer; Carcinoma; Cell Differentiation - genetics; Cytokeratin; Datasets; Epithelial cells; Epithelial Cells - metabolism; Gene expression; Histology; Humans; Immunohistochemistry; Immunological tolerance; Morphology; Myasthenia gravis; Self; single‐cell RNA‐seq; The Cancer Genome Atlas; thymic carcinoma; thymic epithelial tumor; Thymoma - pathology; Thymus; Thymus Gland; Thymus Neoplasms - genetics; Thymus Neoplasms - pathology; Transcription Factors - genetics; Transcription Factors - metabolism; Tumors; thymic carcinoma; single-cell RNA-seq; AIRE; thymic epithelial tumor; bioinformatics; The Cancer Genome Atlas
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5777

Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC‐specific transcriptional regulator that is required for immunological self‐tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA‐seq data in the TCGA‐THYM database. Furthermore, our bioinformatics approach to the recent single‐cell RNA‐seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs. Thymic epithelial tumors originating from thymic epithelial cells (TECs) are classified into six types of thymomas (Type A, AB, B1‐B3 thymomas, and micronodular thymoma with lymphoid stroma [MNT]) and thymic carcinoma (TC). Despite the clear distinction between cortical (cTECs) and medullary TECs (mTECs) in physiology, the cell of origin of each TET has remained enigmatic. In the current study, we confirmed the expression of AIRE, an mTEC‐specific transcriptional regulator, in most TCs at both protein and mRNA levels. Furthermore, our bioinformatics approach has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations, suggesting their cell of origin as mTECs.