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IL-33-ST2-NF-κB 信号通路在前列腺癌中的表达及免疫浸润研究。

Expression and immune infiltration studies of IL-33-ST2-NF-κB signaling pathway in prostate cancer.

机构信息

School of Basic Medical College, Beihua University, Jilin, China.

Department of Rehabilitation, School of Nursing, Jilin University, Changchun, China.

出版信息

Prostate. 2024 Nov;84(15):1398-1410. doi: 10.1002/pros.24778. Epub 2024 Aug 7.

DOI:10.1002/pros.24778
PMID:39113225
Abstract

BACKGROUND

To analyze the expression of interleukin-33 (IL-33), growth-stimulated expression gene 2 (ST2), nuclear factor-kappaB (NF-κB) and immune cell infiltration in prostate cancer, this study aims to provide an experimental basis for the clinical prevention and treatment of prostate cancer.

METHODS

The expression of IL-33 in PCa tissues was analyzed using TCGA, TIMER and HPA databases. Using the UALCAN database, the systematic exploration of the relationship between IL-33 and various clinicopathological parameters was conducted. The correlation between IL-33 expression and immune cell infiltration was investigated using TIMER, CIBERSORT and GEPIA databases. To verify these analyses, 22 cases of normal prostate (NP), 76 cases of benign prostatic hyperplasia (BPH), and 100 cases of PCa were recruited. Immunohistochemical staining was performed to examine the expression of IL-33, ST2, NF-κB, and the infiltration of immune cells. Correlations between these factors were then determined.

RESULTS

The expression of IL-33, ST2 and NF-κB was significantly lower in PCa tissues compared with NP (p < 0.05). IL-33 was not associated with age in PCa but showed associations with race, molecular characteristics, lymph node metastatic status, TP53 mutation and tumor grade. Furthermore, IL-33 was associated with immune cell infiltration. Positive correlations were observed between IL-33 and ST2 expressions, as well as between IL-33 and CD68 macrophages in BPH and PCa.

CONCLUSIONS

IL-33, ST2 and NF-κB are lowly expressed in PCa tissues, their expression decreases with the increasing malignancy of cancer. IL-33, ST2 and NF-κB are factors associated with PCa immune infiltration. IL-33 has an inhibitory effect on prostate cancer through the IL-33/ST2/NF-κB signalling pathway.

摘要

背景

分析白细胞介素-33(IL-33)、生长刺激表达基因 2(ST2)、核因子-κB(NF-κB)和免疫细胞浸润在前列腺癌中的表达,旨在为前列腺癌的临床防治提供实验依据。

方法

采用 TCGA、TIMER 和 HPA 数据库分析 PCa 组织中 IL-33 的表达。利用 UALCAN 数据库系统探讨 IL-33 与各种临床病理参数的关系。采用 TIMER、CIBERSORT 和 GEPIA 数据库研究 IL-33 表达与免疫细胞浸润的相关性。为验证这些分析,招募了 22 例正常前列腺(NP)、76 例良性前列腺增生(BPH)和 100 例 PCa 患者。采用免疫组织化学染色法检测 IL-33、ST2、NF-κB 的表达及免疫细胞浸润情况。然后确定这些因素之间的相关性。

结果

PCa 组织中 IL-33、ST2 和 NF-κB 的表达明显低于 NP(p<0.05)。IL-33 与 PCa 患者的年龄无关,但与种族、分子特征、淋巴结转移状态、TP53 突变和肿瘤分级有关。此外,IL-33 与免疫细胞浸润有关。在 BPH 和 PCa 中,IL-33 与 ST2 表达以及与 CD68 巨噬细胞之间存在正相关关系。

结论

IL-33、ST2 和 NF-κB 在 PCa 组织中低表达,其表达随癌症恶性程度的增加而降低。IL-33、ST2 和 NF-κB 是与 PCa 免疫浸润相关的因素。IL-33 通过 IL-33/ST2/NF-κB 信号通路对前列腺癌具有抑制作用。

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