CD24, NFIL3, FN1, and KLRK1 signature predicts melanoma immunotherapy response and survival.

IF 4.8 3区 医学 Q1 GENETICS & HEREDITY
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.

CD24, NFIL3, FN1和KLRK1信号预测黑色素瘤免疫治疗反应和生存。
黑色素瘤由于其转移倾向和高死亡率而引起严重的健康问题。免疫疗法已经成为一种很有前途的治疗策略,利用病人的免疫系统来对抗肿瘤细胞。然而,并非所有患者对免疫治疗的反应都相同,因此需要预测性生物标志物来识别潜在的应答者并优化治疗策略。利用NanoString nCounter Human Immunology v2 Panel评估的579个免疫相关基因的数据,我们将转录组学数据与35个个体的临床特征相结合,以开发黑色素瘤患者免疫治疗反应的预测特征。通过综合分析,我们鉴定出18个基因在无应答患者中上调,3个基因在应答患者中上调。在多变量分析中,CD24、NFIL3、FN1和KLRK1被确定为预测治疗结果的关键预测因子。然后我们结合这些基因的表达水平计算出一个分数。该评分在区分有反应者和无反应者方面具有较高的准确性,曲线下面积为0.935 (p
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来源期刊
Journal of Molecular Medicine-Jmm
Journal of Molecular Medicine-Jmm 医学-医学:研究与实验
CiteScore
9.30
自引率
0.00%
发文量
100
审稿时长
1.3 months
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.
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