Bruna Pereira Sorroche, Renan de Jesus Teixeira, Vinicius Gonçalves de Souza, Isabela Cristiane Tosi, Katiane Tostes, Ana Carolina Laus, Iara Viana Vidigal Santana, Vinicius de Lima Vazquez, Lidia Maria Rebolho Batista Arantes
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引用次数: 0
Abstract
Melanoma poses a significant health concern due to its propensity to metastasize and its high mortality rate. Immunotherapy has emerged as a promising treatment strategy for harnessing the patient's immune system to fight tumor cells. However, not all patients respond equally to immunotherapy, highlighting the need for predictive biomarkers to identify potential responders and optimize treatment strategies. Using data from 579 immunology-related genes evaluated by the NanoString nCounter Human Immunology v2 Panel, we integrated transcriptomic data with the clinical characteristics of 35 individuals to develop a predictive signature for immunotherapy response in melanoma patients. Through comprehensive analysis, we identified 18 genes upregulated in non-responder patients and three upregulated in responder patients. In multivariate analysis, CD24, NFIL3, FN1, and KLRK1 were identified as key predictors with significant potential for forecasting treatment outcomes. We then calculated a score incorporating the expression levels of these genes. The score achieved high accuracy in discriminating responders from non-responders, with an area under the curve of 0.935 (p < 0.001). The signature was also significantly associated with progression-free survival, overall survival, and survival following immunotherapy (p < 0.001). The validation of the signature in two independent cohorts confirmed its robustness and applicability, with areas under the curve of 0.758 (p = 0.036) and 0.833 (p = 0.004), respectively. This study represents a significant advance in precision medicine for melanoma. By identifying patients unlikely to benefit from immunotherapy, our approach could help optimize treatment allocation and improve patient outcomes. KEY MESSAGES: Novel 4-gene signature predicts immunotherapy failure in melanoma. High accuracy for personalized treatment decisions. Signature associated with decreased survival for non-responders. Signature validated in independent cohorts, enhancing generalizability. Potential to tailor treatment strategies and avoid unnecessary burden to patients.
期刊介绍:
The Journal of Molecular Medicine publishes original research articles and review articles that range from basic findings in mechanisms of disease pathogenesis to therapy. The focus includes all human diseases, including but not limited to:
Aging, angiogenesis, autoimmune diseases as well as other inflammatory diseases, cancer, cardiovascular diseases, development and differentiation, endocrinology, gastrointestinal diseases and hepatology, genetics and epigenetics, hematology, hypoxia research, immunology, infectious diseases, metabolic disorders, neuroscience of diseases, -omics based disease research, regenerative medicine, and stem cell research.
Studies solely based on cell lines will not be considered. Studies that are based on model organisms will be considered as long as they are directly relevant to human disease.