Integrative Analysis of Intestinal Transcriptomes Underscores C2 Upregulation in IBD, AIG, EoE, and CRC

Intestinal transcriptomic data encompass substantial value in studying inflammatory bowel disease. By analyzing intestinal gene expression profiles, this study aimed to discover transcripts exhibiting diagnostic efficacy for IBD. Intestinal transcriptomic data from 1,458 patients with Crohn's disease (CD), 1,211 patients with ulcerative colitis (UC), and 674 healthy controls were acquired by integrating seven datasets with accession numbers GSE66407, GSE193677, GSE126124, GSE83687, GSE75214, GSE36807, and GSE16879. Then, the DEGs in IBD were analyzed by ML methods to discern transcripts that hold diagnostic power. ROC analysis identified potential biomarkers, which were subsequently tested in 16 external datasets. C2, NLRC5, S100P, PGAP3, and GPR15 emerged as prominent genes based on both RF and LASSO methods. Meanwhile, only NLRC5 and C2 had an AUC of the ROC curve greater than the 0.7 threshold in the integrated data. ROC analysis across 23 cohorts demonstrated that the AUC of C2 and NLRC5 were above 0.7 in the majority of the cohorts, particularly that for C2. However, upregulated C2 also exhibited diagnostic efficacy for autoimmune gastritis (AIG), eosinophilic esophagitis (EoE), and colorectal cancer (CRC), reflecting the substantial activation of the complement cascade in these disorders manifesting with gastrointestinal inflammation.