Zhou Lifang, Lu Xu, Qiao Guohong
Department of Clinical Laboratory, Yixing People's Hospital, Affiliated to Jiangsu University, Yixing, 214200, China.
Clin Transl Oncol. 2025 Feb;27(2):745-755. doi: 10.1007/s12094-024-03574-6. Epub 2024 Aug 1.
This study aimed to investigate the relationship between the interferon-gamma (IFN-γ) pathway in different tumor microenvironments (TME) and patients' prognosis, as well as the regulatory mechanisms of this pathway in tumor cells.
Using RNA-seq data from the TCGA database, we analyzed the predictive value of the IFN-γ pathway across various tumors. We employed a univariate Cox regression model to assess the prognostic significance of IFN-γ signaling in different tumor types. Additionally, we analyzed single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to examine the distribution characteristics of the IFN-γ pathway and explore its regulatory mechanisms, highlighting how IFN-γ influenced cellular interactions within the TME.
Our analysis revealed a significant association between the IFN-γ pathway and adverse prognosis in pan-cancer tissues (P < 0.001). Interestingly, this correlation varied regarding positive and negative regulation across different tumor types. Through a detailed examination of scRNA-seq data, we found that the IFN-γ pathway exerted substantial regulatory effects on stromal and immune cells. In contrast, its expression and regulatory patterns in tumor cells exhibited diversity and heterogeneity. Further analysis indicated that the IFN-γ pathway not only enhanced the immunogenicity of tumor cells but also inhibited their proliferation. Cell-cell interaction analysis confirmed the pivotal role of the IFN-γ pathway within the overall regulatory network. Moreover, we identified HMGB2 (high mobility group box 2) in T cells as a potential key regulator of tumor cell proliferation.
The IFN-γ pathway exhibited a dual function by both suppressing tumor cell proliferation and enhancing their immunogenicity, positioning it as a pivotal target for refined cancer diagnosis and cancer strategies.
本研究旨在探讨不同肿瘤微环境（TME）中干扰素-γ（IFN-γ）通路与患者预后之间的关系，以及该通路在肿瘤细胞中的调控机制。
利用来自TCGA数据库的RNA测序数据，我们分析了IFN-γ通路在各种肿瘤中的预测价值。我们采用单变量Cox回归模型评估IFN-γ信号在不同肿瘤类型中的预后意义。此外，我们分析了来自基因表达综合数据库（GEO）的单细胞RNA测序（scRNA-seq）数据，以研究IFN-γ通路的分布特征并探索其调控机制，重点关注IFN-γ如何影响TME内的细胞间相互作用。
我们的分析揭示了IFN-γ通路与泛癌组织不良预后之间存在显著关联（P < 0.001）。有趣的是，这种相关性在不同肿瘤类型的正负调控方面存在差异。通过对scRNA-seq数据的详细检查，我们发现IFN-γ通路对基质细胞和免疫细胞具有实质性的调控作用。相比之下，其在肿瘤细胞中的表达和调控模式表现出多样性和异质性。进一步分析表明，IFN-γ通路不仅增强了肿瘤细胞的免疫原性，还抑制了它们的增殖。细胞间相互作用分析证实了IFN-γ通路在整体调控网络中的关键作用。此外，我们确定T细胞中的高迁移率族蛋白B2（HMGB2）是肿瘤细胞增殖的潜在关键调节因子。
IFN-γ通路通过抑制肿瘤细胞增殖和增强其免疫原性发挥双重功能，使其成为精准癌症诊断和癌症治疗策略的关键靶点。
