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Published on: October 11, 2018
Identification of ERN1 as a Potential Context-Dependent Biomarker in Chronic Obstructive Pulmonary Disease Based on
1Department of Respiratory Medicine, The Third Hospital of Changsha (The Affiliated Changsha Hospital of Hunan University), Changsha, Hunan, 410015, People's Republic of China.
Purpose:
To identify an endoplasmic-reticulum-stress-related candidate gene in chronic obstructive pulmonary disease (COPD) lung tissue and assess its internal discriminative performance and cross-cohort reproducibility.
Patients And Methods:
This bioinformatics study used the GSE57148 lung tissue dataset (98 COPD and 91 subjects with normal-spirometry; all male smokers undergoing lung resection). Differential expression was analyzed using limma on log2 (fragments per kilobase of transcript per million mapped reads [FPKM] + 1), followed by enrichment and protein-protein interaction analyses. Endoplasmic reticulum to nucleus signaling 1 (ERN1) was prioritized using a literature-informed post hoc multi-criteria framework. Internal discrimination was evaluated by receiver operating characteristic (ROC) analysis with repeated stratified 10-fold cross-validation and bootstrap optimism correction. External sensitivity analyses were performed in independent cohorts.
Results:
A total of 308 differentially expressed genes were identified. ERN1 was significantly upregulated in COPD (log2FC = 0.75, adjusted P = 1.98 x 10^-15). In the discovery cohort, ERN1 showed internal discrimination (area under the ROC curve [AUC] = 0.853; cross-validated AUC = 0.848). However, external replication was heterogeneous; in the largest mixed-sex cohort (GSE47460), discrimination was limited (AUC = 0.477), and adjusted external models remained non-significant.
Conclusion:
ERN1 is upregulated in COPD lung tissue in GSE57148 and represents an endoplasmic-reticulum-stress-related, context-dependent candidate signal. Current evidence is preliminary and requires prospective validation in independent, sex-balanced cohorts and clinically accessible biospecimens.