Liu Yuqi, Wang Han, Zhao Shihan, Wang Zhenjiang, Yang Lijuan, Zhang Jihong, Hou Qinlong, Xiao ZiShen, Wang Pengmin, Liu Yanbo
School of Basic Medical College, Beihua University, Jilin 132013, China.
The Pathology Department of Affiliated Hospital, Beihua University, Jilin 132013, China.
Cytokine. 2025 Jan;185:156828. doi: 10.1016/j.cyto.2024.156828. Epub 2024 Dec 9.
Uterine corpus endometrial carcinoma (UCEC) is one of the most common malignant tumours of the female genital tract. In the occurrence, progression and prognosis of UCEC, chronic inflammation plays an important role, making it pivotal to identify inflammatory response-related endometrial diseases. The cytokine interleukin-33 (IL-33) plays significant roles in immune responses, and has been associated with inappropriate allergic reactions, autoimmune diseases, and cancer pathology. In the past decade, studies have begun to uncover the pivotal roles of IL-33 in shaping tumour microenvironment (TME), where it may promote or inhibit tumorigenesis and development depending on the specific tumour types. However, the association between IL-33 expression and UCEC remains unclear. Here we investigated the expression profiles of IL-33 in pan-cancer based on TCGA database. Then, differential gene expression analysis and correlation analysis of IL-33 was investigated in UCEC. In addition, functional enrichment analysis and Kaplan-Meier survival analysis were performed to predict the potential function of IL-33 and its role in the prognosis of UCEC patients. Also, a nomogram model was constructed to predict the prognosis of UCEC. The expression of the inflammatory factor NF-κB p65 and the IL-33, along with its receptor ST2, was analyzed in UCEC tumour tissues and normal tissues of clinical specimens through immunohistochemical staining. Meanwhile, we used toluidine blue staining and methanol Congo red staining to observe the infiltration of mast cells and eosinophils in the endometrial tissue. The results of Kaplan-Meier plotter data indicated that patients with lower IL-33 expression had poorer progression-free interval than those with higher expression. Based on the results of multifactor Cox regression, a nomogram was generated to predict UCEC occurrence risk and prognosis. Clinical specimen characteristics also confirmed a negative correlation between IL-33 expression and UCEC staging and grading. This comprehensive analysis of IL-33, based on bioinformatics and immunohistochemistry, revealed that IL-33 has the function of inhibiting UCEC occurrence and progression and can be served as a beneficial prognostic marker in the clinic.
子宫体子宫内膜癌(UCEC)是女性生殖道最常见的恶性肿瘤之一。在UCEC的发生、发展和预后过程中,慢性炎症起着重要作用,因此识别与炎症反应相关的子宫内膜疾病至关重要。细胞因子白细胞介素-33(IL-33)在免疫反应中发挥重要作用,并与不适当的过敏反应、自身免疫性疾病和癌症病理相关。在过去十年中,研究开始揭示IL-33在塑造肿瘤微环境(TME)中的关键作用,在TME中,根据特定肿瘤类型,它可能促进或抑制肿瘤发生和发展。然而,IL-33表达与UCEC之间的关联仍不清楚。在此,我们基于TCGA数据库研究了IL-33在泛癌中的表达谱。然后,在UCEC中研究了IL-33的差异基因表达分析和相关性分析。此外,进行了功能富集分析和Kaplan-Meier生存分析,以预测IL-33的潜在功能及其在UCEC患者预后中的作用。同时,构建了列线图模型以预测UCEC的预后。通过免疫组织化学染色分析了临床标本的UCEC肿瘤组织和正常组织中炎症因子NF-κB p65以及IL-33及其受体ST2的表达。同时,我们使用甲苯胺蓝染色和甲醇刚果红染色观察子宫内膜组织中肥大细胞和嗜酸性粒细胞的浸润情况。Kaplan-Meier绘图仪数据结果表明,IL-33表达较低的患者无进展生存期比表达较高的患者更差。基于多因素Cox回归结果,生成了列线图以预测UCEC发生风险和预后。临床标本特征也证实了IL-33表达与UCEC分期和分级之间呈负相关。基于生物信息学和免疫组织化学对IL-33的综合分析表明,IL-33具有抑制UCEC发生和发展的功能,可作为临床上有益的预后标志物。