Author:
Qin Lihua,Li Sheng,Cao Xi,Huang Tengjia,Liu Yixin,Chen Ouying
Abstract
AbstractIschemic stroke (IS) is of increasing concern given the aging population and prevalence of unhealthy lifestyles, with older females exhibiting higher susceptibility. This study aimed to identify practical diagnostic markers, develop a diagnostic model for immunogenic cell death (ICD)-associated IS, and investigate alterations in the immune environment caused by hub genes. Differentially expressed genes associated with ICD in IS were identified based on weighted gene co-expression network analysis and the identification of significant modules. Subsequently, machine learning algorithms were employed to screened hub genes, which were further assessed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. A nomogram mode lwas then constructed for IS diagnosis, and its diagnostic value was assessed using a receiver operating characteristic curve. Finally, alterations in immune cell infiltration were assessed within patients with IS, and the pan-cancer expression patterns of hub genes were evaluated. Three hub genes associated with ICD (PDK4, CCL20, and FBL) were identified. The corresponding nomogram model for IS diagnosis could effectively identify older female patients with IS (area under the curve (AUC) = 0.9555). Overall, the three hub genes exhibit good diagnostic value (AUC > 0.8). CCL20 and FBL are significantly associated with the extent of immune cells infiltration. Moreover, a strong link exists between hub gene expression and pan-cancer prognosis. Cumulatively, these results indicate that ICD-related hub genes critically influence IS progression in older females, presenting novel diagnostic and therapeutic targets for personalized treatment.
Funder
the National Natural Science Foundation of China
Disciplinary Reveal System project of Hunan University of Chinese Medicine
Scientific Research Project of Hunan Provincial Health Commission
Project of Hunan Provincial Administration of Traditional Chinese Medicine
Hunan Provincial Natural Science Foundation of China
Discipline construction at Hunan University of Chinese Medicine
Publisher
Springer Science and Business Media LLC
Reference47 articles.
1. World Health Organization. The top 10 causes of death. http://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed on March 2021, (2020).
2. Persky, R. W., Turtzo, L. C. & McCullough, L. D. Stroke in women: Disparities and outcomes. Curr. Cardiol. Rep. 12, 6–13. https://doi.org/10.1007/s11886-009-0080-2 (2010).
3. Cherian, L. Women and ischemic stroke: Disparities and outcomes. Neurol. Clin. 41, 265–281. https://doi.org/10.1016/j.ncl.2022.10.001 (2023).
4. Girijala, R. L., Sohrabji, F. & Bush, R. L. Sex differences in stroke: Review of current knowledge and evidence. Vasc. Med. 22, 135–145. https://doi.org/10.1177/1358863X16668263 (2017).
5. Ahnstedt, H., McCullough, L. D. & Cipolla, M. J. The importance of considering sex differences in translational stroke research. Transl. Stroke Res. 7, 261–273. https://doi.org/10.1007/s12975-016-0450-1 (2016).