Ulcerative colitis (UC) is an idiopathic chronic recurrent inflammatory bowel disease (IBD) occurring in the colon and rectum [[1], [2], [3]]. The cause of UC is elusive and may be linked with microbial, genetic, immune, and environmental factors [[4], [5], [6]]. Its main clinical features are bloody diarrhea, abdominal pain, and tenesmus [7]. The global incidence of UC is on the rise, most commonly affecting individuals between the ages of 20 and 40 [8,9]. According to reports, the highest incidence rate per 100,000 individuals for UC can be observed in Northern Europe (Faroe Islands = 57.9), North America (Canada = 23.1), and Australasia (Australia = 17.4). Northern Europe (Norway = 505) and North America (US = 286) have the highest prevalence rates (per 100,000 people), and in Asia, the prevalence rate is expected to quadruple by 2035 [10]. Therefore, the burden of UC is extremely serious, and if UC is not treated promptly, it can induce more severe diseases, mainly including toxic megacolon, intestinal perforation, and cancer [11,12]. Therefore, early diagnosis of UC patients is critical.

Hypoxia is a key feature of intestinal inflammation [13]. Hypoxia-induced factor-1α (HIF-1α) is the primary regulatory factor in cells’ response to hypoxia [14]. HIF-1α overexpression can trigger NF-κB activation in hypoxic neutrophils, and NF-κB is linked to the pathogenesis of many inflammatory diseases, including UC [[15], [16], [17], [18]]. Furthermore, hypoxia reduces oxidative phosphorylation capacity and ADP-dependent mitochondrial respiration rate, and increases production of reactive oxygen species (ROS) [19]. An increase in ROS would alter intestinal epithelial permeability and disrupt the gut barrier, potentially leading to the development and worsening of UC [[20], [21], [22]]. Therefore, hypoxia plays a critical part in the pathogenesis of UC. Innovating targets related to hypoxia may facilitate early diagnosis of UC patients.

This work screened differentially expressed hypoxia-related genes (DEHRGs) associated with UC, then screened hub genes by building up a protein–protein interaction (PPI) network, and compared their ability to diagnose UC using a receiver operating characteristic (ROC) curve. Finally, potential regulatory miRNAs and transcription factors (TFs) of hub genes were analyzed, and functional enrichment analysis was undertaken. The objective of this work was to examine the value of the hub genes as potential diagnostic biomarkers for UC and provide new ideas for the treatment of this disease.