Rafaqat Saira, Hamid Hafsa, Asif Roha, Asif Muhammad, Tariq Maria, Saleem Malaika, Abaid Hijab
Department of Zoology, Lahore College for Women University, Lahore 54000, Pakistan.
Department of Biotechnology, Lahore College for Women University, Lahore 54000, Pakistan.
World J Gastrointest Oncol. 2025 Jul 15;17(7):107341. doi: 10.4251/wjgo.v17.i7.107341.
This article summarized the role of interleukins (ILs) in the pathogenesis of cholangiocarcinoma (CCA). It discovered a negative feedback mechanism wherein alternative splicing led to the upregulation of the IL 1 receptor antagonist (IL1RN) isoforms IL1RN-201 and IL1RN-203, which play a crucial anti-inflammatory role in -mutant intrahepatic CCA (iCCA). Higher levels of IL-4 receptor were associated with a worse survival rate in patients with CCA. In addition, elevated levels of serum IL-6 have been associated with the start and progression of CCA, a common cancer generated by inflammation. IL-8 was a useful predictor of human hilar CCA. Mechanistically, signal transducer and activator of transcription 3 signaling was used by IL-10 produced from M2-polarized tumor-associated macrophages to enhance the malignant characteristics of iCCA cells. It was suggested that IL-17A and IL-22 have an impact on the development of CCA associated with hepatic fluke infection. The most significant finding was the decreased expression of the IL-23 receptor, a prognostic gene, in iCCA. IL-25 may be a useful prognostic biomarker as aberrant expression of the protein in CCA tissue was linked to tumor spread and a poor prognosis. Tumor cell migration and proliferation were both accelerated by homogenized liver tissue that expressed IL-33 significantly. The correlation between high IL-35 expression and aggressiveness in iCCA highlights it as a useful biomarker for assessing the course and prognosis of iCCA in clinical settings. This article concluded that IL-1, IL-4, IL-6, IL-8, IL-10, IL-17, IL-23, IL-25, IL-33, and IL-35 play significant roles in the pathogenesis of CCA. Further research is required to find the association of other ILs such as IL-2, IL-3, IL-5, IL-7, IL-11, and more in the pathogenesis of CCA.
本文总结了白细胞介素（ILs）在胆管癌（CCA）发病机制中的作用。研究发现了一种负反馈机制，即可变剪接导致IL-1受体拮抗剂（IL1RN）亚型IL1RN-201和IL1RN-203上调，它们在突变型肝内CCA（iCCA）中发挥关键的抗炎作用。较高水平的IL-4受体与CCA患者较差的生存率相关。此外，血清IL-6水平升高与CCA（一种由炎症引发的常见癌症）的发生和进展有关。IL-8是人类肝门部CCA的有用预测指标。从机制上讲，M2极化的肿瘤相关巨噬细胞产生的IL-10利用信号转导和转录激活因子3信号传导来增强iCCA细胞的恶性特征。研究表明，IL-17A和IL-22对与肝吸虫感染相关的CCA发展有影响。最显著的发现是iCCA中作为预后基因的IL-23受体表达降低。IL-25可能是一种有用的预后生物标志物，因为该蛋白在CCA组织中的异常表达与肿瘤扩散和不良预后有关。显著表达IL-33的匀浆肝组织可加速肿瘤细胞迁移和增殖。iCCA中高IL-35表达与侵袭性之间的相关性表明，它是临床环境中评估iCCA病程和预后的有用生物标志物。本文得出结论，IL-1、IL-4、IL-6、IL-8、IL-10、IL-17、IL-23、IL-25、IL-33和IL-35在CCA发病机制中起重要作用。还需要进一步研究以发现其他白细胞介素如IL-2、IL-3、IL-5、IL-7、IL-11等在CCA发病机制中的关联。
