Identification of hypoxia-associated genes as potential diagnostic biomarkers for ulcerative colitis.

BACKGROUND

Incidence of ulcerative colitis (UC) is on the rise globally, highlighting the need for new diagnostic methods to alleviate UC burden.

OBJECTIVES

To explore the value of hypoxia-related genes (HRGs) as UC diagnostic markers.

METHODS

UC-related datasets (GSE87466 and GSE92415) were obtained from GEO database. Differential analysis was undertaken on GSE87466 dataset, followed by intersection analysis of HRGs, thus yielding UC-related differentially expressed HRGs (DEHRGs). Enrichment analyses were undertaken on DEHRGs. Hub genes were identified through a PPI network. Small molecules associated with hub genes were predicted using CMap, and diagnostic value was validated via ROC curves in GSE92415 dataset. Clinical samples of UC were collected and subjected to qRT-PCR for detecting the diagnostic value of hub genes. Potential miRNAs and transcription factors (TFs) that may modulate hub genes, and biological functions and signaling pathways of hub genes, were analyzed.

RESULTS

Our research obtained 28 DEHRGs and used PPI networks to identify 9 hub genes in UC. The prediction of small molecular drugs suggested that chloroquine and pantoprazole were potential drugs to treat UC. ROC results demonstrated that all 9 hub genes had great diagnostic ability (AUC > 0.7), of which PPARGC1A had the best diagnostic value. Detection of clinical samples from UC patients also revealed that the expression of 9 hub genes differed significantly between the UC and the control groups, and this result was consistent with the prediction results from bioinformatics. These 9 hub genes were potentially modulated by 32 miRNAs and 55 TFs. Twenty genes functionally similar to hub genes were identified, which were mainly enriched in biological functions such as response to corticosteroid, negative regulation of MAP kinase activity, and activating transcription factor binding.

CONCLUSION

HRGs play a pivotal part in UC occurrence and progression. Nine hub genes may be promising diagnostic biomarkers for UC.