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Comprehensive pan-cancer analysis reveals SIRT5 is a predictive biomarker for prognosis and immunotherapy response

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Abstract

Background

Sirtuin 5 (SIRT5) is a promising therapeutic target involved in regulating multiple metabolic pathways in cells and organisms. The role of SIRT5 in cancer is currently unclear, and a comprehensive systematic pan-cancer analysis is required to explore its value in diagnosis, prognosis, and immune function.

Methods

We investigated the role of SIRT5 in tumorigenesis, diagnosis, prognosis, metabolic pathways, the immune microenvironment, and pan-cancer therapeutic response. Moreover, we explored chemicals affecting the expression of SIRT5 and computed the relationship between SIRT5 and drug sensitivity. Finally, the role of SIRT5 in melanoma was analyzed using a series of experiments in vitro and in vivo.

Results

We found that SIRT5 is differentially expressed and shows early diagnostic value in various tumors and that somatic cell copy number alterations and DNA methylation contribute to its aberrant expression. SIRT5 expression correlates with clinical features. Besides, it is negatively (positively) correlated with several metabolic pathways and positively (negatively) correlated with several important metastasis-related and immune-related pathways. High SIRT5 expression predicts poor (or good) prognosis in various tumors and can affect drug sensitivity. We also demonstrated that SIRT5 expression significantly correlates with immunomodulator-associated molecules, lymphocyte subpopulation infiltration, and immunotherapeutic response biomarkers. In addition, we showed that SIRT5 is differentially expressed in immunotherapy cohorts. In addition, we explored various chemicals that may affect SIRT5 expression. In conclusion, we demonstrated that SIRT5 is a key pathogenic gene that promotes melanoma progression.

Conclusion

Our study provides a systematic analysis of SIRT5 and its regulatory genes. SIRT5 has excellent diagnostic and prognostic capabilities for many cancers. This may remodel the tumor microenvironment. The potential of SIRT5-based cancer therapies is emphasized and helps predict the response to immunotherapy.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

This work was supported by funding from the Natural Science Foundation of Hebei Provence (No. H2022206368/No. H2022206446), Natural Science Foundation of China (MianShang project: No. 82372519), Medical Science Research Program of Hebei Provincial Health Commission (No. 20241603).

Author information

Authors and Affiliations

  1. Department of Dermatology, The Third Hospital of Hebei Medical University, No.139 Ziqiang Road, Qiaoxi District, Shijiazhuang, Hebei Province, 050051, China

    Yacong Ji, Yaling Liu & Shaomin Shi

  2. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Chongyang Li

  3. State Key Laboratory of Resource Insects, Southwest University, Chongqing, 400715, China

    Sicheng Wan

  4. Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA

    Kui Zhang

  5. Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA

    Kui Zhang

Authors
  1. Yacong Ji
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  2. Chongyang Li
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  3. Sicheng Wan
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  4. Kui Zhang
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  5. Yaling Liu
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  6. Shaomin Shi
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Contributions

Y. J., C. L., Y. L., and S. S. designed and supervised the study. Y. J., C. L., and S. W. performed the experiments. K. Z. and Y. J. analyzed the experimental data. S. S. and Y. J. wrote the manuscript. Y. L. revised the manuscript. All contributing authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yaling Liu or Shaomin Shi.

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All animal experiments were supervised and approved by the Committee of Animal Protection and Ethics of Southwest University.

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Not applicable.

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The authors declare no competing interests.

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Ji, Y., Li, C., Wan, S. et al. Comprehensive pan-cancer analysis reveals SIRT5 is a predictive biomarker for prognosis and immunotherapy response. Funct Integr Genomics 24, 60 (2024). https://doi.org/10.1007/s10142-024-01338-7

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  • DOI: https://doi.org/10.1007/s10142-024-01338-7

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