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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1466806
This article is part of the Research Topic Immunological Precision Therapeutics: Integrating Multi-Omics Technologies and Comprehensive Approaches for Personalized Immune Intervention View all 26 articles

Pan-cancer and experimental analyses reveal the immunotherapeutic significance of CST2 and its association with stomach adenocarcinoma proliferation and metastasis

Provisionally accepted
Dan Huang Dan Huang 1Jing Li Jing Li 1*Zhijun He Zhijun He 1*Wenjing Liang Wenjing Liang 1*Likun Zhong Likun Zhong 1*Jun Huang Jun Huang 1*Yinteng Wu Yinteng Wu 2*Shijian Zhao Shijian Zhao 3*
  • 1 Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
  • 2 Department of Orthopedic and Trauma Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
  • 3 Department of Cardiology, the Affiliated Cardiovascular Hospital of Kunming Medical University (Fuwai Yunnan Cardiovascular Hospital), Kunming, China

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

    Purpose: Cystatin 2 (CST2) is a cysteine protease inhibitor, and recent research suggests its potential involvement in cancer development. However, its role in the occurrence, progression, and prognosis of pan-cancer has not been systematically investigated.This study comprehensively analyzes the differential expression of CST2 in pan-cancer. The expression distribution patterns of CST2 were examined using single-cell datasets. Furthermore, we conducted a comprehensive evaluation of the correlation between CST2 expression and various factors. These factors include prognosis, immune cell infiltration, immune-related genes, mutations, methylation, tumor mutation burden (TMB), and microsatellite instability (MSI). In addition, we analyzed the sensitivity of drugs dependent on CST2 expression. We utilized gene set enrichment analysis (GSEA) analysis to explore the biological functions of CST2 across different cancer types. Finally, in gastric cancer cell lines, we will investigate the impact of CST2 knockout on expression levels, clonal proliferation, cell apoptosis, and cell migration.Results ： CST2 exhibits abnormal overexpression in multiple tumors. Single-cell analysis reveals high expression of CST2 in fibroblasts. CST2 is closely associated with prognosis, immune cell infiltration, immune-related genes, mutations, methylation, TMB, and MSI. Enrichment analysis demonstrated a significant correlation between CST2 and immune-related pathways. In stomach adenocarcinoma (STAD), CST2related risk models are associated with prognosis and demonstrate strong predictive capabilities, while also being closely linked to the immune microenvironment. Drug sensitivity analysis indicates the correlation between CST2 and 21 chemotherapy drugs.Finally, experimental validation revealed significantly elevated expression of CST2 in STAD, indicating its role as a driver gene in regulating malignant cell proliferation and migration.Conclusion：CST2 serves as a potential tumor immune biomarker, playing a critical facilitating role in the proliferation and migration processes of STAD.

    Keywords: Cystatin 2 (CST2), Pan-cancer, Stomach adenocarcinoma (STAD), the tumor microenvironment (TME), Immunotherapy, single-cell

    Received: 18 Jul 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Huang, Li, He, Liang, Zhong, Huang, Wu and Zhao. 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:
    Jing Li, Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
    Zhijun He, Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
    Wenjing Liang, Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
    Likun Zhong, Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
    Jun Huang, Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Region, China
    Yinteng Wu, Department of Orthopedic and Trauma Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
    Shijian Zhao, Department of Cardiology, the Affiliated Cardiovascular Hospital of Kunming Medical University (Fuwai Yunnan Cardiovascular Hospital), Kunming, 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.