Yue Chaomin, Zheng Xiao, Ye Yuqing, Li Danyang, Zhou Yanhong
Department of Obstetrics and Gynaecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of General Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Mol Biosci. 2025 Apr 24;12:1566363. doi: 10.3389/fmolb.2025.1566363. eCollection 2025.
Ovarian cancer is a serious disease that is a danger to a woman's life and health and is currently being extensively studied worldwide. TNFAIP8L3, a member of the tumor necrosis family, plays a significant role in tumor immune regulation; however, its role in ovarian cancer has not been fully studied and reported.
This study used data from 381 cases of ovarian cancer (OVCA) from The Cancer Genome Analysis (TCGA)-OV to analyze the clinical phenotype and immune phenotype of TNFAIP8L3. Pearson correlation coefficients and protein-protein interaction (PPI) network analyses were used to identify potential biological functions and the genes co-expressed with TNFAIP8L3. The Gene Set Enrichment Analysis (GSEA) method was used to evaluate the relevant regulatory pathways of TNFAIP8L3. Gene Set Variation Analysis was performed to evaluate the proportions of 24 immune cell types in OVCA. Finally, a nomogram and multivariate COX regression analysis were performed to prove the independent prognostic value of TNFAIP8L3 in OVCA.
A total of 181 genes were co-expressed with TNFAIP8L3, including 163 positively correlated and 18 negatively correlated genes. The co-expressed genes associated with TNFAIP8L3 were significantly enriched in biological processes such as cell activation involved in immune response and leukocyte activation involved in immune response. Pathway analysis of TNFAIP8L3 further revealed the association of TNFAIP8L3 with the TGF-β signaling pathway and antigen processing and presentation pathways, especially with macrophages and neutrophils in the antigen presentation process. Moreover, the expression of TNFAIP8L3 was significantly high in OVCA and other solid tumors to function as an independent risk factor for the prognosis of OVCA, with important research value for the prognosis of patients with OVCA.
Those findings indicate that TNFAIP8L3 is correlated with antigen processing and presentation pathways in macrophages and neutrophils and affects prognosis and immune infiltration in OVCA.
卵巢癌是一种严重威胁女性生命健康的疾病，目前正在全球范围内进行广泛研究。肿瘤坏死因子家族成员TNFAIP8L3在肿瘤免疫调节中发挥重要作用；然而，其在卵巢癌中的作用尚未得到充分研究和报道。
本研究使用来自癌症基因组分析（TCGA）-卵巢癌（OV）的381例卵巢癌（OVCA）数据，分析TNFAIP8L3的临床表型和免疫表型。采用Pearson相关系数和蛋白质-蛋白质相互作用（PPI）网络分析来确定潜在的生物学功能以及与TNFAIP8L3共表达的基因。使用基因集富集分析（GSEA）方法评估TNFAIP8L3的相关调控途径。进行基因集变异分析以评估OVCA中24种免疫细胞类型的比例。最后，构建列线图并进行多变量COX回归分析，以证明TNFAIP8L3在OVCA中的独立预后价值。
共有181个基因与TNFAIP8L3共表达，其中163个呈正相关，18个呈负相关。与TNFAIP8L3共表达的基因在免疫反应中涉及的细胞活化和免疫反应中涉及的白细胞活化等生物学过程中显著富集。TNFAIP8L3的通路分析进一步揭示了TNFAIP8L3与TGF-β信号通路以及抗原加工和呈递通路的关联，特别是在抗原呈递过程中与巨噬细胞和中性粒细胞的关联。此外，TNFAIP8L3在OVCA和其他实体瘤中的表达显著升高，可作为OVCA预后的独立危险因素，对OVCA患者的预后具有重要研究价值。
这些发现表明TNFAIP8L3与巨噬细胞和中性粒细胞中的抗原加工和呈递通路相关，并影响OVCA的预后和免疫浸润。
