https://orcid.org/0000-0001-5062-555X
Abstract
Background
The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not all cases have been successful due to the complex and variable mechanisms of melanoma response to immune checkpoint inhibition.
Methods
We synthesized collagen-coding gene expression data (second-generation and single-cell sequencing) from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as Metascape database, Gene Set Cancer Analysis (GSCA) database, and Cytoscape software, etc., to investigate the biological mechanisms that may be related with collagens. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of Nidogen-2 (NID2).
Results
Melanoma patients can be divided into two collagen clusters. Patients with high collagen levels (C1) had a shorter survival than those with low collagen levels (C2) and were less likely to benefit from immunotherapy. We demonstrated that NID2 is a potential key factor in the collagen phenotype, is involved in fibroblast activation in melanoma, and forms a barrier to limit the proximity of CD8+ T cells to tumor cells.
Conclusion
We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.
Data Sharing Statement
Prof. Hui Shen can be contacted ([email protected]) regarding the availability of data and materials.
Ethics Approval and Consent to Participate
The study’s protocol was approved by the ethics committee of the Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, and informed consent was obtained from clinicians and patients (approval number: 2020-78-1). The study was in accordance with the declaration of Helsinki.
Consent for Publication
All authors have given consent for publication.
Acknowledgments
The authors gratefully acknowledge contributions from the GEO and TCGA databases.
Author Contributions
All authors made a significant contribution to the work reported, whether in study conception, design, and execution; data acquisition, analysis, and interpretation; or all these areas. All authors were involved in drafting, revising, or critically reviewing the article; gave final approval for the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflicts of interest in this work.