{"doi":"10.1101/2022.06.16.22276291","title":"Peripheral Blood Gene Expression at 3 to 24 Hours Correlates with and Predicts 90-Day Outcome Following Human Ischemic Stroke","abstract":"Abstract This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes and an early gene profile that predicted 90-day outcomes. Peripheral blood from the CLEAR trial IS patients was compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome (NIHSS-NIH Stroke Scale, mRS-modified Rankin Scale). The expression of 467, 526, and 571 genes measured at ≤3, 5 and 24 hours after IS, respectively, were associated with poor 90-day mRS outcome (mRS=3-6), while 49, 100 and 35 associated with good mRS 90-day outcome (mRS=0-2). Poor outcomes were associated with up-regulated MMP9 , S100A12 , interleukin-related and STAT3 pathways. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome. Poor outcome modules were enriched in down-regulated T cell and monocyte-specific genes plus up-regulated neutrophil genes and good outcome modules were associated with erythroblasts and megakaryocytes. Using the difference in gene expression between 3 and 24 hours, 10 genes correctly predicted 100% of patients with Good 90-day mRS outcome and 67% with Poor mRS outcome (AUC=0.88) in a validation set. The predictors included AVPR1A , which mediates platelet aggregation, release of coagulation factors and exacerbates the brain inflammatory response; and KCNK1 ( TWIK-1 ), a member of a two-pore potassium channel family, which like other potassium channels likely modulates stroke outcomes. This study suggests the immune response after stroke impacts long-term functional outcomes. Furthermore, early post-stroke gene expression may predict stroke outcomes and outcome-associated genes could be targets for improving outcomes.","journal":"medRxiv","year":2022,"id":309451,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":321210,"name":"Bodie Knepp","orcid":"0000-0002-0761-8060","position":1,"is_corresponding":false},{"id":321212,"name":"Fernando Rodríguez","orcid":"0000-0001-7582-482X","position":2,"is_corresponding":false},{"id":303685,"name":"Glen C. Jickling","orcid":"0000-0003-3543-0820","position":3,"is_corresponding":false},{"id":306074,"name":"Heather Hull","orcid":null,"position":4,"is_corresponding":false},{"id":303683,"name":"Paulina Carmona-Mora","orcid":"0000-0001-8560-1232","position":5,"is_corresponding":false},{"id":888475,"name":"Cheryl Bushnell","orcid":"0000-0002-3162-7610","position":6,"is_corresponding":false},{"id":303684,"name":"Bradley P. Ander","orcid":"0000-0003-2320-7920","position":7,"is_corresponding":false},{"id":303689,"name":"Frank R. Sharp","orcid":"0000-0002-5642-1459","position":8,"is_corresponding":false},{"id":303690,"name":"Boryana Stamova","orcid":"0000-0002-5440-8816","position":9,"is_corresponding":false},{"id":303688,"name":"Hajar Amini","orcid":"0000-0001-9364-7839","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-19T00:33:11.579763Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}