Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients

Zhiyong Yang; Guanghui Wang; Nan Luo; Chi Kwan Tsang; Li'an Huang

doi:10.3389/fneur.2022.937501

Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients

Front Neurol. 2022 Aug 5:13:937501. doi: 10.3389/fneur.2022.937501. eCollection 2022.

Authors

Zhiyong Yang^{1

2}, Guanghui Wang^{1

2}, Nan Luo^{1

2}, Chi Kwan Tsang¹, Li'an Huang^{1

2}

Affiliations

¹ Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² Department of Neurology, The First Clinical Medical School of Jinan University, Guangzhou, China.

Abstract

Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis. Remarkably, the pre-ranked gene set enrichment analysis revealed that the co-expression modules with subgroup I-specific signature genes significantly overlapped with the differentially expressed genes in AIS patients with hemorrhagic transformation (HT). With respect to subgroup II, exclusively male patients with decreased proteasome activity were identified. Intriguingly, the majority of subgroup III was composed of female patients who showed a comparatively lower level of AIS-induced immunosuppression (AIIS). In addition, we discovered a non-linear relationship between female age and subgroup-specific gene expression, suggesting a gender- and age-dependent alteration of peripheral immunity. Taken together, our novel AIS classification approach could facilitate immunomodulatory therapies, including the administration of gender-specific therapeutics, and attenuation of the risk of HT and AIIS after ischemic stroke.

Keywords: acute ischemic stroke; consensus clustering; immunosuppression; molecular subgroups; peripheral immunity; restricted cubic spline functions.