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探索GIPC2作为与增强免疫反应相关的结直肠癌关键预后标志物。

Exploring GIPC2 as a key prognostic marker in colorectal cancer linked to enhanced immune response.

作者信息

Gu Jiaoyang, Qi Xing, Yu Bin, Wang Yanan, Zhang Liting, Li Shuai, Xin Yu

机构信息

Department of Gastroenterology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Gastrointestinal Endoscopy Center, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Immunobiology. 2025 Jul;230(4):153090. doi: 10.1016/j.imbio.2025.153090. Epub 2025 Jun 17.

Abstract

BACKGROUND

Emerging evidence indicates a potential association between aberrant expression of GIPC PDZ Domain Containing Family member 2 (GIPC2) and the progression of colorectal cancer (CRC). However, the detailed characteristics of GIPC2 expression and its prognostic implications in CRC remain to be thoroughly elucidated.

METHODS

This study retrospectively analyzed the transcriptome profiles and clinical parameters of CRC patients using five publicly available datasets. We used the online database to analyze the prognostic value and subcellular localization of GIPC2 in CRC. Furthermore, comparisons were made between the GIPC2-high and GIPC2-low groups regarding survival prognosis, enriched pathways, genomic mutation status, immune cell infiltration, and TIDE scores using a comprehensive suite of bioinformatics tools. In vitro experiments validated the biological functions of GIPC2 in CRC.

RESULTS

The mRNA expression of GIPC2 was significantly lower in CRC samples than in the adjacent mucosa tissues. A negative correlation was observed between GIPC2 expression and tumor mutation burden, microsatellite instability, as well as tumor immune escape. Notably, higher levels of GIPC2 expression were associated with improved survival outcomes in CRC patients. Furthermore, GIPC2 expression was predominantly detected in non-malignant epithelial cells and was closely linked to an enhanced immune response, potentially through the inhibition of extracellular matrix remolding in CRC. Additionally, GIPC2 downregulation could enhance the proliferation, migration, and invasion capabilities of CRC cells in vitro.

CONCLUSIONS

GIPC2 may serve as a potential prognostic marker for CRC patients. Its expression is significantly correlated with the immune response in CRC.

摘要

背景

新出现的证据表明,含GIPC PDZ结构域家族成员2(GIPC2)的异常表达与结直肠癌(CRC)的进展之间可能存在关联。然而,GIPC2在CRC中的详细表达特征及其预后意义仍有待深入阐明。

方法

本研究使用五个公开可用的数据集对CRC患者的转录组谱和临床参数进行了回顾性分析。我们利用在线数据库分析了GIPC2在CRC中的预后价值和亚细胞定位。此外,使用一套综合的生物信息学工具,对GIPC2高表达组和低表达组在生存预后、富集通路、基因组突变状态、免疫细胞浸润和TIDE评分方面进行了比较。体外实验验证了GIPC2在CRC中的生物学功能。

结果

CRC样本中GIPC2的mRNA表达明显低于相邻黏膜组织。观察到GIPC2表达与肿瘤突变负担、微卫星不稳定性以及肿瘤免疫逃逸之间呈负相关。值得注意的是,CRC患者中较高水平的GIPC2表达与改善的生存结果相关。此外,GIPC2表达主要在非恶性上皮细胞中检测到,并且可能通过抑制CRC中的细胞外基质重塑与增强的免疫反应密切相关。此外,GIPC2下调可增强CRC细胞在体外的增殖、迁移和侵袭能力。

结论

GIPC2可能作为CRC患者的潜在预后标志物。其表达与CRC中的免疫反应显著相关。

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