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

Immunobiology

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

Published: July 2025


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Article 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.

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http://dx.doi.org/10.1016/j.imbio.2025.153090DOI Listing

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