Prognostic value and clinical significance of IL-33 expression in patients with uterine corpus endometrial carcinoma

Abstract

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.