Screening and Preliminary Validation of Parthanatos-Related Key Genes in Asthma Using Transcriptomic and Machine Learning Approaches

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Jiawei Zhao,1,* Danni Li,2,* Chunli Yang,3 Chunyan Liu,1 Xiaolin Ma1 1Department of Pediatrics, The Fifth Affiliated Hospital of Dali University (Baoshan People’s hospital), Baoshan, People’s Republic of China; 2Department of Neonatology, The Fifth Affiliated Hospital of Dali University (Baoshan People’s hospital), Baoshan, People’s Republic of China; 3Department of Gynecology, The Fifth Affiliated Hospital of Dali University (Baoshan People’s Hospital), Baoshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaolin Ma, Baoshan People’s Hospital, Qingyang Road& Longquan Road, Longyang District, Baoshan, Yunnan, People’s Republic of China, Tel +8613312791321, Email Martin606@163.comPurpose: Parthanatos, a Poly polymerase 1 mediated programmed cell death pathway, remains poorly characterized in asthma pathogenesis. This study integrated transcriptomic data from public asthma datasets and parthanatos-related genes (PRGs) to identify the key molecular players.Patients and Methods: Asthma-related datasets GSE69683 (411 asthma and 87 control samples) and GSE134544 (10 asthma and 21 control samples) were obtained from public databases. Through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning, three genes (ANXA3, CEACAM6, and 8d) were prioritized. Functional enrichment linked these genes to inflammatory and metabolic pathways, including complement/coagulation cascades, spliceosomes, and citrate cycle.Results: Immune infiltration analysis revealed significant disparities in naive B cells, eosinophils, neutrophils, resting mast cells, and CD8 + T cells between asthmatic and control groups. These genes are correlated with lung injury, neoplasms, and broader respiratory diseases, highlighting their clinical relevance. Predictive analysis identified environmental compounds (eg benzo(a)pyrene, and estradiol) interacting with all three genes, suggesting therapeutic targets. Preliminary experimental validation via RT-qPCR suggested the upregulation of CEACAM6 and CRISP3 expression in asthmatic blood samples.Conclusion: In conclusion, we identified and preliminarily validated ANXA3, CEACAM6, and CRISP3 as parthanatos-related key genes in asthma, providing a foundational gene signature for subsequent research into asthma diagnostics and mechanisms. Keywords: asthma, parthanatos, key genes, enrichment analysis, immune infiltration

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