IFN-λ在肿瘤中具有双重功能，其抑癌作用已经得到充分确认。然而，内源性IFN-λ可能存在负面的“促肿瘤”效应，其机制尚未完全理解。我们对不同癌症类型中IFN-λ基因的扰乱进行了全面的回顾和分析。利用相关系数研究内源性IFN-λ表达与临床因素、免疫细胞浸润、肿瘤微环境和免疫治疗反应之间的关系。通过构建与IFN-λ相关的基于相关性的网络和KEGG通路中的基因相互作用网络，获得与IFN-λ共同作用的基因，并将从网络中获得的IFN-λ相关基因整合为预后模型的候选标记物。接下来，我们应用单变量和多变量COX回归模型，选取与IFN-λ相关的癌症特异性独立预后标志物，并通过生存分析研究这些基因的危险因素。此外，我们还使用计算方法分析与IFN-λ相关的患者群的转录组、拷贝数变异、遗传突变和甲基化情况。IFN-λ的内源性表达与癌症患者的不良预后相关，其中IFN-λ2和IFN-λ3基因作为独立的预后标志物。IFN-λ与STAT1、STAT2和STAT3等相关基因共同作用，影响JAK-STAT信号通路，促进肿瘤进展。IFN-λ基因的异常与免疫检查点和免疫细胞浸润的变化相关，进而影响癌症和免疫相关通路。IFN-λ表达患者中存在增加的免疫细胞浸润，但这并不改善生存预后，因为T细胞功能障碍和炎症环境也同时存在。IFNL2和IFNL3拷贝数变异的扩增驱动患者中IFN-λ的特异性内源性表达，而这种特定表达与TP53基因的突变增多和DNA甲基化水平降低相关。我们的研究整合了多组学数据，对内源性IFN-λ的负面作用进行了全面的探索，为癌症领域的进一步发现和治疗探索提供了基础资源。 © 2023. BioMed Central Ltd., part of Springer Nature.

IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ''tumor-promoting'' effect of endogenous IFN-λ is still not fully understood.We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups.Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation.Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.© 2023. BioMed Central Ltd., part of Springer Nature.