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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1490623

Leveraging Single-Cell and Multi-Omics Approaches to Identify MTOR-Centered Deubiquitination

Provisionally accepted
Kang Tian Kang Tian 1,2*Ziang Yao Ziang Yao 3Da Pan Da Pan 4*
  • 1 Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, China
  • 2 Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 3 Peking University, Beijing, Beijing Municipality, China
  • 4 Wenzhou Central Hospital, Wenzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Background: Esophageal squamous cell carcinoma (ESCC) remains a significant challenge in oncology due to its aggressive nature and heterogeneity. As one of the deadliest malignancies, ESCC research lags behind other cancer types. The balance between ubiquitination and deubiquitination processes plays a crucial role in cellular functions, with its disruption linked to various diseases, including cancer.Methods: Our study utilized diverse analytical approaches, encompassing Cox regression models, single-cell RNA sequencing, intercellular communication analysis, and Gene Ontology enrichment. We also conducted mutation profiling and explored potential immunotherapeutic agents. Furthermore, in vitro cellular experiments and in vivo mouse models were performed to validate findings. These methodologies aimed to establish deubiquitination-related gene signatures (DUBRGs) for predicting ESCC patient outcomes and response to immunotherapy.: By integrating datasets from TCGA-ESCC and GSE53624, we developed a 14-gene DUBRG model. This signature effectively forecasts ESCC prognosis, drug responsiveness, and immune cell infiltration patterns. It also influences the mutational landscape of patients. Those classified as high-risk exhibited reduced survival rates, increased genetic alterations, and more complex cellular interactions, potentially explaining their poor outcomes. Notably, in vitro and in vivo experiments identified MTOR, a key component of the DUBRG signature, as a promising therapeutic target for ESCC treatment. Conclusion: Our research highlights the significance of 14 DUBRGs in ESCC progression. The risk score derived from this gene set enables clinical stratification of patients into distinct prognostic groups. Moreover, MTOR emerges as a potential target for personalized ESCC therapy, offering new avenues for treatment strategies.

    Keywords: esophageal squamous cell carcinoma, deubiquitination, TCGA, Prognostic model, multi-omics

    Received: 03 Sep 2024; Accepted: 28 Nov 2024.

    Copyright: © 2024 Tian, Yao and Pan. 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:
    Kang Tian, Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, China
    Da Pan, Wenzhou Central Hospital, Wenzhou, 325000, Zhejiang 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.