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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1578909
This article is part of the Research TopicHarnessing Big Data for Precision Medicine: Revolutionizing Diagnosis and Treatment StrategiesView all 39 articles
OAS Family Activation Drives Esophageal Cancer Progression: A Pan-Cancer Tumor Microenvironment and Immunotherapy Responsiveness Analysis
Provisionally accepted- 1Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China
- 2Key Laboratory of Surgery Critical Care and Life Support, Ministry of Education, Xi'an Jiaotong University, Xi’an, China
- 3Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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The OAS (2'-5'-oligoadenylate synthetase) family represents a group of interferon (IFN)-inducible enzymes with established antiviral properties. However, their pathophysiological roles in cancer development and progression remain poorly characterized.: Through pan-cancer analysis, we systematically evaluated genomic alterations, mRNA expression patterns, and prognostic significance of four OAS family members (OAS1, OAS2, OAS3, and OASL). The OAS activation score was computed using the GSVA algorithm. Subsequent investigations focused on elucidating its associations with tumor microenvironment (TME) characteristics and clinical responses to immunotherapy. The impact of OASL on apoptosis, migration, and invasion was validated in esophageal carcinoma cell lines. Result: Our multi-omics analysis systematically characterized OAS family expression profiles and genomic alterations across malignancies. The GSVA-derived OAS score demonstrated significant correlations with TME remodeling in most cancer types. Additionally, OAS family regulates antigen processing machinery and immune checkpoint ligand, through IFN-α/γand IL-6/JAK/STAT3 pathways in tumor cells. Survival analysis indicated high OAS score patients showed significantly prolonged overall survival and progression free survival (P<0.05). Validation experiments were conducted in ESCA and confirmed these findings. Conclusion: This pan-cancer study establishes the OAS family as critical modulators of tumor microenvironment dynamics. Quantitative OAS scoring may serve as a novel stratification tool for identifying immunotherapy-sensitive patient subpopulations.
Keywords: OAS family, Pan-cancer, Tumor microenvironments, Immunotherapy, TCGA
Received: 18 Feb 2025; Accepted: 11 Apr 2025.
Copyright: © 2025 Zhao, Chen, Xiaoya, Xie, Chai, Ye and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shiyuan Liu, Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, 710004, Shaanxi Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.