Research Article

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

‡These authors have contributed equally to this work and share first authorship

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Anqi Lin‡

https://orcid.org/0000-0002-6324-0410

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

‡These authors have contributed equally to this work and share first authorship

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Tianqi Gu‡

https://orcid.org/0000-0002-2815-5595

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China

‡These authors have contributed equally to this work and share first authorship

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Shuang Hou

https://orcid.org/0009-0006-7655-4976

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

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Jiarong Yao

https://orcid.org/0000-0003-3097-8619

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

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Peng Luo

*Author for correspondence:

E-mail Address: luopeng@smu.edu.cn

https://orcid.org/0000-0002-8215-2045

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

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Jian Zhang

**Author for correspondence:

E-mail Address: zhangjian@i.smu.edu.cn

https://orcid.org/0000-0001-7217-0111

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China

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Published Online:16 Aug 2023https://doi.org/10.2217/imt-2022-0175

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Abstract

Aims: There is an urgent need for appropriate biomarkers that can precisely and reliably predict immunotherapy efficacy, as immunotherapy responses can differ in skin cutaneous melanoma (SKCM) patients. Methods: In this study, univariate regression models and survival analysis were used to examine the link between calcium voltage-gated channel subunit alpha 1C (CACNA1C) mutation status and immunotherapy outcome in SKCM patients receiving immunotherapy. Mutational landscape, immunogenicity, tumor microenvironment and pathway-enrichment analyses were also performed. Results: The CACNA1C mutation group had a better prognosis, higher immunogenicity, lower endothelial cell infiltration, significant enrichment of antitumor immune response pathways and significant downregulation of protumor pathways. Conclusion:CACNA1C mutation status is anticipated to be a biomarker for predicting melanoma immunotherapy effectiveness.

Plain language summary

Aims: The treatment to make the immune system work better is also used to treat a skin cancer called skin cutaneous melanoma (SKCM). We need new ways to predict if the treatment will work. Methods: We looked at two groups of people getting the treatment to make the immune system work better. One group had a special change in their bodies, and the other group did not. We looked at how this change affected the patients. We also looked at how to make their immune system stronger. Results: We found that people with mutations tend to have better chances of getting better from their sickness. Conclusion: We think that this might be a good way to tell if immunotherapy will work well for this type of SKCM.

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This study examined the relationship between mutation status and prognosis and the possible mechanisms. The results suggest CACNA1C mutation status is a potential biomarker for SKCM immunotherapy.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 15

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Received 9 July 2022

Accepted 7 July 2023

Published online 16 August 2023

Published in print October 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/imt-2022-0175

Author contributions

Y Huang, A Lin and T Gu made substantial contributions to the conception and/or design of the work, the acquisition, analysis and interpretation of data for the work, and critically drafting or revising the work for important intellectual content. S Hou and J Yao also contributed to the acquisition, analysis and/or interpretation of data for the work. P Luo and J Zhang provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

This work was supported by the Natural Science Foundation of Guangdong Province (grant nos. 2018A030313846 and 2021A1515012593) and the National Natural Science Foundation of China (grant nos. 81802257, 81871859, 81772457, 82172750 and 82172811). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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CACNA1C mutation as a prognosis predictor of immune checkpoint inhibitor in skin cutaneous melanoma

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