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白细胞介素-38 促进前列腺癌的发展。

IL-38 promotes the development of prostate cancer.

机构信息

Department of Pathology, Tongji Hospital, Tongji University, Shanghai, China.

Department of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Front Immunol. 2024 May 8;15:1384416. doi: 10.3389/fimmu.2024.1384416. eCollection 2024.

Abstract

INTRODUCTION

Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment.

MATERIALS AND METHODS

The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics.

RESULTS

There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38/CD8 group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients.

CONCLUSION

These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

摘要

简介

前列腺癌(PCa)仍然是男性癌症相关死亡率的一个重大关注点。肿瘤的发展是由肿瘤细胞及其微环境之间复杂的相互作用所调控的,因此确定哪些是影响肿瘤微环境中 PCa 进展的关键因素是至关重要的。

材料和方法

本研究利用组织病理学和免疫组织化学来确定 IL-38 在 PCa 中的表达,并分析了 IL-38 在 PCa 中的表达水平与临床病理特征之间的相关性。

结果

与相邻的非 PCa 组织相比,PCa 组织中 IL-38 的表达显著增加(P<0.0001)。此外,在增殖指数高的肿瘤细胞中,IL-38 的表达显著高于增值指数低的肿瘤细胞。ROC 曲线分析表明,IL-38 对 PCa 的诊断具有较高的特异性和敏感性(AUC=0.76)。此外,我们通过免疫荧光双重染色探究了前列腺癌组织中 IL-38 的细胞来源。此外,在 PCa 中,IL-38 的表达与 CD8 和 PD-1 的表达水平呈负相关。生存分析显示,IL-38 高表达的 PCa 患者总体生存率显著降低(P=0.0069),当 IL-38 与 CD8 共表达时,IL-38/CD8 组的生存率显著降低。多变量分析表明,IL-38 的表达水平和 TNM 分期是 PCa 患者生存的独立预测因素。

结论

这些发现表明,IL-38 在 PCa 的发展中起着关键作用,探索 IL-38 与肿瘤微环境中各种免疫因子之间的相关性进一步揭示了其作用机制,使其成为 PCa 免疫治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eca1/11109393/f422ed1db9f5/fimmu-15-1384416-g001.jpg

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