Exploring Hypoxia-related Genes as Prognostic Indicators in Lung Adenocarcinoma
Bandar Alghamdi, Sonia Rocha
Abstract
Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, with hypoxia contributing to tumor progression and treatment resistance. Identifying hypoxia-related biomarkers could enhance prognosis and therapeutic strategies for LUAD.
Introduction
Lung Adenocarcinoma and Hypoxia Lung cancer remains one of the most common and deadly cancers worldwide, with non-small cell lung cancer (NSCLC) being the dominant histological subtype. Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of NSCLC and represents a major clinical and biological focus within this disease category due to its distinct molecular and genetic characteristics. Although advances in molecular profiling and targeted therapies have improved the management of NSCLC, the prognosis for patients with LUAD remains poor, particularly in advanced stages.
Materials and Methods:
In this study, we utilized multiple datasets to identify differentially expressed genes (DEGs) associated with tumorigenesis. To identify DEGs between tumor and normal samples, we employed the LIMMA package, applying a stringent cutoff of |log2FC| > 0.585 and an adjusted p-value < 0.05. Following DEG identification, we specifically targeted hypoxia-related differentially expressed genes (HRDEGs), which were selected through a Venn diagram approach.
Discussion
Lung adenocarcinoma remains one of the leading causes of cancer-related mortality worldwide, with hypoxia recognized as a key contributor to tumor progression, metastasis, and therapy resistance. In this study, we comprehensively analyzed hypoxia-related differentially expressed genes (HRDEGs) in LUAD and identified 283 upregulated and 322 downregulated HRDEGs, reflecting the broad impact of hypoxic signaling on multiple cellular processes.
Acknowledgments
We thank all the members of the scientific community for making their datasets public.
Citation: Alghamdi B, Rocha S (2026) Exploring hypoxia-related genes as prognostic indicators in lung adenocarcinoma. PLoS One 21(6): e0349820. https://doi.org/10.1371/journal.pone.0349820
Editor: Hongtao Bi, Northwest Institute of Plateau Biology Chinese Academy of Sciences, CHINA
Received: September 17, 2025; Accepted: May 4, 2026; Published: June 3, 2026.
Copyright: © 2026 Alghamdi, Rocha. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are publicly available. The transcriptomic and genomic datasets analyzed in this study were retrieved from publicly accessible repositories, including GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas). Specific accession numbers and dataset identifiers are provided within the manuscript. Accession numbers and links are: GSE18842; GSE13213; https://www.cbioportal.org/study/summary?id=luad_tcga. No new data were generated.
Funding: This study was supported by the Wellcome Trust to SR (206293/Z/17/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
