Introduction: This study aims to integrate bioinformatics analysis with a single-center prospective cohort to explore alternative spliced genes and their relationships with clinical outcomes in sepsis. Methods: Alternative splicing (AS) events were identified using GSE185263 dataset. Logistic regression models were constructed to evaluate the association between differential AS events and in-hospital mortality in patients with sepsis. Patients admitted to the ICU of Zhongda Hospital between December 2023 and February 2025 were enrolled. Peripheral blood samples were collected within 24 hours of admission. RT-PCR was used to validate transcript variants of selected target genes, while RT-qPCR was performed to measure gene expression levels.The primary outcome was 28-day mortality. Cox proportional hazards models were used to assess the association between AS events and 28-day mortality. The optimal cutoff value was determined by maximizing the Youden Index. Results: A total of 6475 AS events were identified using a threshold of |ΔMean Percent Spliced In| > 0.05. Logistic regression analysis revealed 31 AS events significantly associated with in-hospital mortality. Among these, five events involving OLAH, CPNE1, CASP8, TCF7, and MAX which are related to sepsis prognosis were included for validation. A cohort of 144 sepsis patients was enrolled, and blood samples from 12 randomly selected patients (6 deceased and 6 survivors) were used for validation. Only exon 4 skipping in OLAH showed a significant difference between the two groups, whereas AS events in the other four genes did not show statistical differences. Compared to survivors, deceased patients exhibited significantly higher expression of OLAH and an increased proportion of exon 4 skipping. Multivariate Cox regression analysis revealed that while overall OLAH expression level was not associated with 28-day mortality, the proportion of exon 4 skipping was independently correlated with increased 28-day mortality (HR 1.76 95%CI 1.291-2.419 P < 0.01). AUC for predicting 28-day mortality based on OLAH exon 4 skipping was 0.834 (95% CI 0.753–0.915). Using a cutoff value of 0.706, sensitivity and specificity were 69.6% and 84.3%. Conclusions: Increased ratio of OLAH exon 4 skipping is associated with elevated 28-day mortality in patients with sepsis.
Wang et al. (Sun,) studied this question.