Document Type

Article

Publication Date

3-21-2025

Comments

This article is the author’s final published version in International Journal of Molecular Sciences, Volume 26, Issue 7, April 2025, Article number 2848.

The published version is available at https://doi.org/10.3390/ijms26072848. Copyright © 2025 by the authors. Licensee MDPI, Basel, Switzerland.

Abstract

Hypercapnia is a key feature of the respiratory microenvironment in many pathologic conditions. It occurs both as a regional and as a systemic process, and it is associated with multiple metabolic changes such as mitochondrial dysfunction, decreased ATP production, and metabolic shift from glycolytic energy production to fatty acid metabolism. In the cancer tumor microenvironment, hypercapnia has been linked at times to enhanced cell migration, invasion, and chemoresistance. Our previous work has shown that hypercapnia-associated gene signatures can be used as prognostic biomarkers. However, unlike the hypoxia-inducible factor pathway, there are no validated targets to quantify hypercapnia. In this study, we investigated the phenotypic and transcriptomic changes occurring in pancreatic ductal adenocarcinoma (PDAC) due to chronic exposure to hypercapnic atmospheres. We then identified and validated SIAH3 as a hypercapnia-affected target and explored its clinical relevance as a prognostic factor in PDAC.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

40243415

Language

English

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