Abstract：
The functions of immunosenescence are closely related to skin cutaneous melanoma (SKCM). The aim of this study is to uncover the characteristics of immunosenescence index (ISI) to identify novel biomarkers and potential targets for treatment. Firstly, integrated bioinformatics analysis was carried out to identify risk prognostic genes, and their expression and prognostic value were evaluated. Then, we used the computational algorithm to estimate ISI. Finally, the distribution characteristics and clinical significance of ISI in SKCM by using multi-omics analysis. Patients with a lower ISI had a favorable survival rate, lower chromosomal instability, lower somatic copy-number alterations, lower somatic mutations, higher immune infiltration, and sensitive to immunotherapy. The ISI exhibited robust, which was validated in multiple datasets. Besides, the ISI is more effective than other published signatures in predicting survival outcomes for patients with SKCM. Single-cell analysis revealed higher ISI was specifically expressed in monocytes, and correlates with the differentiation fate of monocytes in SKCM. Besides, individuals exhibiting elevated ISI levels could potentially receive advantages from chemotherapy, and promising compounds with the potential to target high ISI were recognized. The ISI model is a valuable tool in categorizing SKCM patients based on their prognosis, gene mutation signatures, and response to immunotherapy.
摘要：
皮肤黑素瘤（SKCM）与免疫衰老的功能密切相关。这项研究的目的是揭示免疫衰老指数（ISI）的特征，以确定新的生物标志物和潜在的治疗靶标。首先,进行了综合生物信息学分析，以确定风险预后基因，并评估其表达和预后价值。然后，我们使用计算算法来估计ISI。最后,运用多组学方法分析ISI在SKCM中的分布特点及临床意义。ISI较低的患者有良好的生存率，较低的染色体不稳定性，较低的体细胞拷贝数改变，较低的体细胞突变，较高的免疫浸润，对免疫疗法敏感。ISI表现出强劲的，在多个数据集中进行了验证。此外,在预测SKCM患者的生存结局方面,ISI比其他已发表的特征更有效.单细胞分析显示，较高的ISI在单核细胞中特异性表达，并与SKCM中单核细胞的分化命运相关。此外,表现出升高的ISI水平的个体可能会从化疗中获得优势，并确认了具有靶向高ISI潜力的有前景的化合物。ISI模型是根据SKCM患者的预后对其进行分类的有价值的工具，基因突变签名，和对免疫疗法的反应。
