不同的内源和外源突变过程导致体细胞突变和突变特征的特定模式。尽管他们的生物学研究一直很深入，但只有很少的研究评估突变特征可能的预后作用。我们使用癌症基因组图谱的数据来研究 18 种恶性肿瘤的突变特征活性与四个生存终点之间的关联。我们根据头颈鳞状细胞癌中的 HPV 状态和肺癌中的吸烟状态等进一步探讨了预后差异。使用曲线模型下的动态区域评估特征随时间的预测能力，并分析突变特征活性与基因表达模式差异之间的联系。在 18 种研究的癌症类型中的 12 种中，我们发现了至少一种突变特征，在调整既定的预后因素后，其活性可预测生存结果。例如，总体生存率与九种癌症类型中的突变特征活性相关，以及七种癌症类型中的疾病特异性生存率。类似时钟的特征 SBS5 和 SBS40 最常与生存终点相关。肌球蛋白结合蛋白和黑色素瘤抗原家族的基因是低活性和高活性特征之间失调最严重的基因。基因表达的差异还揭示了各种丰富的途径。根据这些数据，特定的突变特征与基因表达相关，并有可能成为多种癌症类型的强预后因素。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease-specific survival in seven cancer types. The clock-like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.