Identification of ZNF331 as a Biomarker for Obstructive Sleep Apnea in Idiopathic Pulmonary Fibrosis Through Integrated Bioinformatics Analysis and Clinical Validation.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF), yet symptom-based screening frequently lacks reliability in this population. We aimed to identify a blood-based biomarker for detecting OSA in patients with IPF. METHODS: Public peripheral-blood transcriptomic datasets for OSA and IPF were analyzed to identify shared candidate genes. The leading candidate, ZNF331, was validated by reverse transcription-quantitative polymerase chain reaction in an independent clinical cohort comprising normal controls, patients with OSA, and non-oxygen-dependent patients with IPF. Diagnostic performance was assessed using receiver operating characteristic analysis and further corroborated through adjusted and internal validation analyses. RESULTS: ZNF331 was prioritized as a shared candidate gene through the integrated bioinformatics analysis and was subsequently selected for clinical validation. In the validation cohort, ZNF331 expression exhibited an overall downward trend across the normal control, OSA, IPF, and IPF + OSA groups, reaching its lowest levels in patients with IPF complicated by OSA. ZNF331 demonstrated high diagnostic accuracy in differentiating IPF + OSA from IPF-only cases (area under the curve = 0.932, 95% confidence interval 0.874-0.990), whereas the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale showed limited diagnostic utility. The association between reduced ZNF331 expression and the IPF-OSA phenotype remained robust after propensity score matching and internal validation. CONCLUSIONS: ZNF331 is a promising candidate blood-based biomarker for identifying OSA in patients with IPF. Its association with the IPF-OSA phenotype is supported by transcriptomic discovery, clinical validation, and robustness analyses. These findings suggest that ZNF331 may serve as a valuable screening biomarker for this population.