Abstract
AB020. Transforming growth factor-beta 1 as an active biomarker along with programmed cell death ligand-1 expression for the malignant potential in thymic epithelial tumors
Chiaki Nakazono1, Satoru Okada1, Shunta Ishihara1, Masanori Shimomura1, Tatsuo Furuya1, Kenji Kameyama1, Daichi Kakibuchi1, Stefan Küffer2, Denise Müller2, Alexander Marx2, Philipp Ströbel2, Masayoshi Inoue1
1Division of Thoracic Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan;
2Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
Correspondence to: Satoru Okada, MD, PhD. Division of Thoracic Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: s-okada@koto.kpu-m.ac.jp.
Background: Thymic epithelial tumors (TETs) are relatively rare malignant mediastinal tumors. The molecular and biological prognostic factors and therapeutic targets in TETs remain unclear. We previously reported that high programmed cell death ligand-1 (PD-L1) expression in TETs was associated poor prognosis (Ishihara S, Lung Cancer, 2020). This study investigated the significance of transforming growth factor-beta 1 (TGF-β1) expression on tumor progression, postoperative prognosis, and PD-L1 expression in TETs.
Methods: This study included patients with thymomas and thymic carcinomas who underwent surgical resection at the University Hospital, Kyoto Prefectural University of Medicine (Kyoto, Japan) between April 2001 and March 2020. This retrospective analysis included 92 patients with surgically resected thymomas (n=79) and thymic carcinomas (n=13). TGF-β1, PD-L1, pSmad2, and pSmad3 expression were evaluated using immunohistochemistry. The associations between TGF-β1 expression and clinicopathological features, freedom from recurrence (FFR) and other biological molecules were assessed. The impact of TGF-β1 on PD-L1 expression was investigated in thymic cell carcinoma cell lines.
Results: High TGF-β1 expression was detected in 28% (26 of 92) of patients. High TGF-β1 expression was associated with Masaoka stage III/IV (advanced) disease. The 5-year FFR rates differed significantly between the high and low TGF-β1 groups (58.1% vs. 95.1%, P<0.001, log-rank). High TGF-β1 and PD-L1 co-expression was associated with the worst FFR (46.1%) and was an independent factor for poor prognosis. Immunohistochemistry revealed a positive correlation between TGF-β1 and PD-L1 and pSmad2/3 expression. Moreover, PD-L1 expression increased in a TGF-β1 dose-dependent manner, along with pSmad2/3 up-regulation in vitro.
Conclusions: High TGF-β1 and PD-L1 expression could be a poor prognostic factor in patients with TETs undergoing surgical resection. These patients also showed up-regulation of PD-L1 expression by TGF-β1 through the Smad pathway. This pathway might promote PD-L1-dependent immune suppression and lead to poor prognosis in TETs.
Keywords: Thymic epithelial tumor (TET); transforming growth factor-beta (TGF-β); programmed cell death ligand-1 (PD-L1); Smad pathway; prognostic factor
Acknowledgments
Funding: This study was partly supported by a Uehara Memorial Foundation Research Fellowship awarded to S.O.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-ab020/coif). P.S. serves as an unpaid editorial board member of Mediastinum from May 2023 to April 2025. S.O. reports this study was partly supported by a Uehara Memorial Foundation Research Fellowship. 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 institutional ethics board of Kyoto Prefectural University of Medicine (No. ERB-C-931) and individual consent for this retrospective analysis was waived.
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-ab020
Cite this abstract as: Nakazono C, Okada S, Ishihara S, Shimomura M, Furuya T, Kameyama K, Kakibuchi D, Küffer S, Müller D, Marx A, Ströbel P, Inoue M. AB020. Transforming growth factor-beta 1 as an active biomarker along with programmed cell death ligand-1 expression for the malignant potential in thymic epithelial tumors. Mediastinum 2024;8:AB020.
