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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1491808
This article is part of the Research Topic Harnessing Molecular Insights for Enhanced Drug Sensitivity and Immunotherapy in Cancer View all articles

Identification of anoikis-related molecular patterns and the novel risk model to predict prognosis, tumor microenvironment infiltration and immunotherapy response in bladder cancer

Provisionally accepted
Luochen Zhu Luochen Zhu 1Feng Xiao Feng Xiao 2Yi Hou Yi Hou 3Shenjun Huang Shenjun Huang 4*Yanyan Xu Yanyan Xu 1*Xiaohong Guo Xiaohong Guo 1*Xinwei Dong Xinwei Dong 1*Chunlu Xu Chunlu Xu 5Xiaolei Zhang Xiaolei Zhang 6Haijuan Gu Haijuan Gu 1*
  • 1 Department of pharmacy, Nantong tumor hospital, Nantong, China
  • 2 Department of pharmacy, Nantong third people's hospital, Nantong, China
  • 3 Department of pharmacy, Zhongjiang people's hospital, Zhongjiang, China
  • 4 Department of Oncology,Nantong Tumor Hospital, Nantong, Jiangsu Province, China
  • 5 Department of Andrology, Nanjing Drum Tower Hospital, Nanjing, Liaoning Province, China
  • 6 Department of Urology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China

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

    Anoikis, a unique form of cell death, serves as a vital part of the organism's defense by preventing shedding cells from re-attaching to the incorrect positions, which plays a pivotal role in cancer metastasis. Nonetheless, the specific mechanisms between anoikis and the clinical prognosis and tumor microenvironment (TME) of bladder cancer (BLCA) are insufficiently understood. BLCA patients were classified into two anoikis subtypes based on the expression of candidate anoikis-related genes (ARGs) in the study. Compared to ARGcluster A, patients assigned to ARGcluster B were characterized by an immunosuppressive microenvironment and worse prognosis.Subsequently, an anoikis-related model was constructed, incorporating PLOD1, EHBP1, and CSPG4. Patients with bladder cancer (BLCA) in the low-risk group exhibited a more favorable prognosis.Then, the anoikis-related model, including PLOD1, EHBP1, and CSPG4, was constructed, and BLCA patients in the low-risk group were characterized by a better prognosis. Next, the accurate nomogram was built to improve the clinical applicability. Moreover, immune infiltration and clinical features differed significantly between the high-risk group and low-risk groups. We also found that the low-risk group exhibited a lower tumor immune dysfunction and exclusion score, a higher immunophenoscore (IPS), and were more sensitive to immunotherapy. Eventually, the expression levels of three genes were verified by our experiment, and knockdown of PLOD1 could inhibit invasion and migration abilities in BLCA cell lines. These results demonstrated a new direction in precision therapy for BLCA, and indicated that the ARGs might be helpful to in predicting prognosis and as therapeutic targets in BLCA.

    Keywords: Bladder cancer, Anoikis, prognosis, Tumor Microenvironment, PLOD1

    Received: 05 Sep 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Zhu, Xiao, Hou, Huang, Xu, Guo, Dong, Xu, Zhang and Gu. 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:
    Shenjun Huang, Department of Oncology,Nantong Tumor Hospital, Nantong, 226000, Jiangsu Province, China
    Yanyan Xu, Department of pharmacy, Nantong tumor hospital, Nantong, China
    Xiaohong Guo, Department of pharmacy, Nantong tumor hospital, Nantong, China
    Xinwei Dong, Department of pharmacy, Nantong tumor hospital, Nantong, China
    Haijuan Gu, Department of pharmacy, Nantong tumor hospital, Nantong, 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.