A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab

Autor:	Iyad Kobeissi, Islam Eljilany, Tala Achkar, William A. LaFramboise, Lucas Santana-Santos, Ahmad A. Tarhini
Rok vydání:	2023
Předmět:	Inorganic Chemistry Organic Chemistry biomarkers immunotherapy melanoma miRNA microRNA General Medicine Physical and Theoretical Chemistry Molecular Biology Spectroscopy Catalysis Computer Science Applications
Zdroj:	International Journal of Molecular Sciences; Volume 24; Issue 9; Pages: 8167
ISSN:	1422-0067
DOI:	10.3390/ijms24098167
Popis:	Despite the unprecedented advances in the treatment of melanoma with immunotherapy, there continues to be a major need for biomarkers of clinical benefits and immune resistance associated with immune checkpoint inhibitors; microRNA could play a vital role in these efforts. This study planned to identify differentially expressed miRNA molecules that may have prognostic value for clinical benefits. Patients with surgically operable regionally advanced melanoma were treated with neoadjuvant ipilimumab (10 mg/kg intravenously every 3 weeks × two doses) bracketing surgery. Tumor biospecimens were obtained at baseline and surgery, and microRNA (miRNA) expression profiling was performed on the tumor biopsies. We found that an expression profile consisting of a 4-miRNA signature was significantly associated with improved relapse-free survival (RFS). The signature consisted of biologically relevant molecules previously reported to have prognostic value in melanoma and other malignancies, including miR-34c, miR-711, miR-641, and miR-22. Functional annotation analysis of target genes for the 4-miRNA signature was significantly enriched for various cancer-related pathways, including cell proliferation regulation, apoptosis, the MAPK signaling pathway, and the positive regulation of T cell activation. Our results presented miRNAs as potential biomarkers that can guide the treatment of melanoma with immune checkpoint inhibitors. These findings warrant further investigation in relation to CTLA4 blockade and other immune checkpoint inhibitors. ClinicalTrials.gov NCT00972933.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad62ce23227b63ea485307794aef51f0 https://doi.org/10.3390/ijms24098167 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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