Dados do Resumo

Título

Identifying a 4-gene signature for predicting overall survival in melanoma patients

Introdução

Melanoma poses a significant threat due to its ability to spread rapidly and lead to high mortality rates. While advancements in immunotherapy offer promising avenues for harnessing the immune system to combat the disease, maximizing patient outcomes hinges on identifying reliable biomarkers of survival.

Objetivo

To identify potential biomarkers of overall survival (OS) in melanoma patients treated with anti-PD-1 immunotherapy.

Métodos

We analyzed the gene expression profiles of 35 melanoma samples using the nCounter NanoString platform. A gene signature associated with OS was constructed by applying a multivariate Cox regression analysis to identify significant genes. Their regression coefficients were then multiplied with corresponding gene expression values to create a scoring system. The performance of this signature was validated using an independent cohort of 109 melanoma patients with RNA-sequencing data from The Cancer Genome Atlas (TCGA) accessed through cBioPortal. Statistical analyses were performed using nSolverAnalysis v3.0, SPSS v23.0, and the survminer package in R v4.2.0. The study was approved by the Barretos Cancer Hospital Ethics Committee (#1772/2019).

Resultados

Clinicopathological features such as age, sex, tumor location, histological subtype, Breslow thickness, ulceration, mitosis index, clinical staging, and BRAF mutation status were not predictors of OS in this cohort. From the 594 evaluated genes, 13 were negatively and 7 were positively associated with OS. Multivariate analysis identified a 4-gene signature (p < 0.001) comprising HLA-DQB1, HLA-DRB1, NFIL3 and CD14. Only CD14 was overexpressed in patients with higher OS. An optimal cut-off value of 0.699 was established for OS prediction. Patients with higher scores showed significantly lower OS (p < 0.001). The signature was then applied to the TCGA cohort for validation. The optimal cut-off value of 0.194 was defined in this cohort, and patients with higher scores also exhibited lower OS (p = 0.038).

Conclusões

Our study identified and validated a 4-gene signature associated with melanoma patient survival, suggesting its use as a potential prognostic biomarker. This could enhance melanoma risk assessment and personalized treatment.

Financiador do resumo

This work was supported by the Grupo Español Multidisciplinar de Melanoma (GEM); the São Paulo Research Foundation (grant number 2019/07111-9); and the Researchers Assistance and Incentive Program (PAIP - Barretos Cancer Hospital)

Palavras Chave

Metastatic melanoma; immunotherapy; overall survival