Abstract
Background Immunotherapy offers a novel approach for the treatment of cutaneous melanoma, but the clinical efficiency varies for individual patients. In consideration of the high cost and adverse effects of immunotherapy, it is essential to explore the predictive biomarkers of outcomes. Recently, the tumor mutation burden (TMB) has been proposed as a predictive prognosticator of the immune response. Method RNA-seq and somatic mutation datasets of 472 cutaneous melanoma patients were downloaded from The Cancer Genome Atlas (TCGA) database to analyze mutation type and TMB. Differently expressed genes (DEGs) were identified for functional analysis. TMB-related signatures were identified via LASSO and multivariate Cox regression analysis. The association between mutants of signatures and immune cells was evaluated from the TIMER database. Furthermore, the Wilcox test was applied to assess the difference in immune infiltration calculated by the CIBERSORT algorithm in risk groupings. Results C>T substitutions and TTN were the most common SNV and mutated gene, respectively. Patients with low TMB presented poor prognosis. DEGs were mainly implicated in skin development, cell cycle, DNA replication, and immune-associated crosstalk pathways. Furthermore, a prognostic model consisting of eight TMB-related genes was developed, which was found to be an independent risk factor for treatment outcome. The mutational status of eight TMB-related genes was associated with a low level of immune infiltration. In addition, the immune infiltrates of CD4+ and CD8+ T cells, NK cells, and M1 macrophages were higher in the low-risk group, while those of M0 and M2 macrophages were higher in the high-risk group. Conclusion Our study demonstrated that a higher TMB was associated with favorable survival outcome in cutaneous melanoma. Moreover, a close association between prognostic model and immune infiltration was identified, providing a new potential target for immunotherapy.
Highlights
Cutaneous melanoma, characterized by high aggressiveness and poor prognosis, is well known as a common malignant neoplasm of the skin having the highest mortality rates [1, 2]
SPRR2F 0.036618 1.037297 1.01223 1.062985 0.003347 while it was lower in patients with advanced TN stage. These results revealed that a higher tumor mutation burden (TMB) contributed to a better prognosis in cutaneous melanoma
The greater the presence of new antigens, the more likely these will be recognized by the immune system, indicating the crucially significant role of TMB in immune checkpoint inhibitors (ICIs) therapy
Summary
Cutaneous melanoma, characterized by high aggressiveness and poor prognosis, is well known as a common malignant neoplasm of the skin having the highest mortality rates [1, 2]. It is classified into different subtypes, including the lentigo malignant type, the superficial spreading type, and the nodular type based on clinical and histological characteristics [3]. A prognostic model consisting of eight TMB-related genes was developed, which was found to be an independent risk factor for treatment outcome. The mutational status of eight TMB-related genes was associated with a low level of immune infiltration. A close association between prognostic model and immune infiltration was identified, providing a new potential target for immunotherapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Computational and mathematical methods in medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
