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

IF 2.5 4区 医学 Q3 IMMUNOLOGY
Jiaoyang Gu , Xing Qi , Bin Yu , Yanan Wang , Liting Zhang , Shuai Li , Yu Xin
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引用次数: 0

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.
探索GIPC2作为结直肠癌的关键预后标志物与增强免疫反应相关
越来越多的证据表明,GIPC PDZ结构域含家族成员2 (GIPC2)的异常表达与结直肠癌(CRC)的进展之间存在潜在的关联。然而,GIPC2表达的详细特征及其在结直肠癌中的预后意义仍有待彻底阐明。方法利用5个公开的数据集,回顾性分析结直肠癌患者的转录组谱和临床参数。我们利用在线数据库分析了GIPC2在结直肠癌中的预后价值和亚细胞定位。此外,利用一套全面的生物信息学工具,比较了gipc2高组和gipc2低组在生存预后、富集途径、基因组突变状态、免疫细胞浸润和TIDE评分方面的差异。体外实验验证了GIPC2在结直肠癌中的生物学功能。结果GIPC2 mRNA在结直肠癌组织中的表达明显低于癌旁粘膜组织。GIPC2表达与肿瘤突变负荷、微卫星不稳定性、肿瘤免疫逃逸呈负相关。值得注意的是,高水平的GIPC2表达与CRC患者生存结果的改善相关。此外,在非恶性上皮细胞中主要检测到GIPC2表达,并且与增强的免疫应答密切相关,可能通过抑制CRC的细胞外基质重塑。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可作为结直肠癌患者的潜在预后指标。在结直肠癌中,其表达与免疫应答显著相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
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