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探索EPHX4在胰腺癌中的功能和预后作用:来自生物信息学和实验验证的见解

Exploring the functional and prognostic roles of EPHX4 in pancreatic cancer: Insights from bioinformatics and experimental validation.

作者信息

Huang Shaoyang, Gu Dandan, Xiong Wei

机构信息

College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.

Department of Gastroenterology, Northeast Yunnan Regional Central Hospital, Zhaotong 657000, China.

出版信息

Gene. 2025 Aug 5;959:149504. doi: 10.1016/j.gene.2025.149504. Epub 2025 Apr 19.

Abstract

BACKGROUND

Epoxide hydrolase-4 (EPHX4) belongs to the epoxide hydrolase enzyme family, but its biological function remains unclear, especially its potential involvement in the development of pancreatic tumours. This research sought to examine the function of EPHX4 in pancreatic adenocarcinoma (PAAD).

METHODS

The expression of EPHX4 across cancers was examined through The Cancer Genome Atlas (TCGA). Bioinformatics was employed, leveraging multiple databases to investigate EPHX4 gene expression in pancreatic cancer and its association with survival prognosis, functional enrichment, immune infiltration, tumour mutation load, and drug sensitivity, among other variables. To evaluate EPHX4 expression in PAAD cells, Western blotting and reverse transcription quantitative PCR were used. A series of in vitro functional experiments was performed to assess the proliferation, migration, and invasion of PAAD cells.

RESULTS

EPHX4 expression was markedly elevated in a number of malignancies, including PAAD, and was associated with patient sex, clinical stage, and metastasis to the lymph nodes. High EPHX4 expression was significantly associated with a worse outcome in PAAD patients. According to functional and enrichment studies, EPHX4 is involved in many signalling pathways linked to cancer. The study of immune infiltration revealed that EPHX4 was connected to the existence of a variety of immune cells inside the tumour. Our study revealed that EPHX4 knockdown significantly decreased PAAD cell migration, proliferation, and invasion.

CONCLUSION

EPHX4 is highly expressed in PAAD and independently predicts poor survival. Functional experiments demonstrate its tumor-promoting effects. Its involvement in multiple cancer-related signaling pathways and immune regulation mechanisms highlights the dual prognostic and therapeutic potential of EPHX4 in PAAD.

摘要

背景

环氧化物水解酶-4(EPHX4)属于环氧化物水解酶家族,但其生物学功能仍不清楚,尤其是其在胰腺肿瘤发生发展中的潜在作用。本研究旨在探讨EPHX4在胰腺腺癌(PAAD)中的功能。

方法

通过癌症基因组图谱(TCGA)研究EPHX4在各种癌症中的表达情况。利用生物信息学,借助多个数据库研究EPHX4基因在胰腺癌中的表达及其与生存预后、功能富集、免疫浸润、肿瘤突变负荷和药物敏感性等变量的关系。为评估EPHX4在PAAD细胞中的表达,采用了蛋白质免疫印迹法和逆转录定量PCR。进行了一系列体外功能实验,以评估PAAD细胞的增殖、迁移和侵袭能力。

结果

EPHX4在包括PAAD在内的多种恶性肿瘤中表达明显升高,且与患者性别、临床分期及淋巴结转移有关。PAAD患者中EPHX4高表达与较差的预后显著相关。根据功能和富集研究,EPHX4参与了许多与癌症相关的信号通路。免疫浸润研究表明,EPHX4与肿瘤内多种免疫细胞的存在有关。我们的研究表明,敲低EPHX4可显著降低PAAD细胞的迁移、增殖和侵袭能力。

结论

EPHX4在PAAD中高表达,可独立预测预后不良。功能实验证明其具有促肿瘤作用。其参与多种癌症相关信号通路和免疫调节机制,凸显了EPHX4在PAAD中的双重预后和治疗潜力。

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