Abstract
AB028. Spatial transcriptomics to dissect the cellular heterogeneity in thymic carcinoma
Minoru Matsumoto1, Yasuyo Saijo1, Koichi Tsuneyama2, Takeshi Oya1
1Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;
2Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
Correspondence to: Minoru Matsumoto, MD, PhD. Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Email: m.matsumoto@tokushima-u.ac.jp.
Background: Thymic epithelial cells (TECs) consist of two distinct components: cortical TECs (cTECs) and medullary TECs (mTECs), which are crucial for the positive and negative selection of thymocytes, respectively. Among thymic epithelial tumors (TETs) originating from TECs, thymic carcinomas (TCs) exhibit the worst prognosis. While the cell of origin of TCs has long been enigmatic, our previous study has demonstrated that TCs reflect the signature of mTECs utilizing bioinformatics approaches and immunohistochemistry of autoimmune regulator (AIRE), a molecule specific to mTECs. However, the cellular heterogeneity of TCs relevant to their pathogenesis remains elusive. It motivated us to dissect the tumor heterogeneity in more detail.
Methods: To investigate the cancer ecosystem underlying TCs, we have conducted a comprehensive spatial transcriptome analysis on two cases of TCs. We also utilized the bulk RNA-seq dataset of TETs from The Cancer Genome Atlas project archive and single-cell RNA-seq datasets of normal TECs and TC from the public database, ensuring the validity of our findings.
Results: Our spatial transcriptome analysis identified the spatial distribution of key molecules associated with TCs. While the well-known TC markers, KIT and CD5, were broadly expressed across the tumor tissues, the expression of AIRE was sporadic, mirroring its distribution in the normal thymus. Unsupervised clustering also identified a distinct cluster with a high level of AIRE expression, and this cluster expressed genes relevant to AIRE-expressing mTECs in the normal thymus, suggesting that mTEC heterogeneity was maintained in TC to some extent. Furthermore, re-analysis of single-cell RNA-seq data on TC revealed the existence of unique tumor subpopulations resembling thymic myoid cells and post-AIRE mTECs. Our spatially aware analysis also highlighted a unique gene module localized at the margin of tumor nests.
Conclusions: Spatial transcriptomics has given us new insights into the biology of TCs, further suggesting the cellular heterogeneity in TCs associated with mTECs. These findings have significant implications for our understanding of TCs and their pathogenesis.
Keywords: Thymic carcinoma (TC); medullary thymic epithelial cell (mTEC); transcriptomics
Acknowledgments
Funding: This work was supported by JSPS KAKENHI (No. 23K14478, to M.M.).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-ab028/coif). M.M. reports funding from JSPS KAKENHI (No. 23K14478). K.T. reports funding from JSPS KAKENHI (No. 22K07024). The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Tokushima University Hospital (No. 4107-1) and informed consent was obtained from all individual participants.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/med-24-ab028
Cite this abstract as: Matsumoto M, Saijo Y, Tsuneyama K, Oya T. AB028. Spatial transcriptomics to dissect the cellular heterogeneity in thymic carcinoma. Mediastinum 2024;8:AB028.
