Aimed at Subtype Discrimination but Yielding a Shared Marker: Integrative Analysis of Blood Transcriptomes Reveals Upregulated TLR5 as a Potential Biomarker for IBD.

BACKGROUND: Despite the similarities, Crohn's disease (CD) and ulcerative colitis (UC), the two major subtypes of inflammatory bowel disease (IBD), exhibit distinctions. The increasing burden of IBD necessitates discovering novel diagnostic markers. Considering the importance of distinguishing between CD and UC in selecting therapeutic strategies in clinical settings, this investigation focused on identifying subtype-specific blood biomarkers.

METHODS: The discovery set was formed by integrating five blood transcriptomic datasets, including GSE119600, GSE126124, GSE94648, GSE86434, and GSE71730, which incorporated samples from CD, UC, and controls. After determining DEGs in CD and UC, they were separately filtered according to WGCNA and then analyzed by LASSO and RF algorithms. Eventually, ROC analysis of the diagnostic performances was conducted independently in the datasets used for discovery. Moreover, ROC analysis was implemented in independent cohorts to assess the generalizability of findings.

RESULTS: Initially, the identified subtype-specific candidate biomarkers included INPPL1, TLR5, SLC9A8, IMPDH1, and GRK6 for CD, and IL4R, ACAA1, NARF, and RRM2 for UC. However, external validation only accentuated the promising diagnostic potential of TLR5 for CD. However, TLR5 was nonspecific for CD and also acts as a potential biomarker for UC. While this study did not unveil subtype-specific diagnostic markers capable of stratifying CD from UC, the upregulated TLR5 was identified as a shared biomarker for both subtypes.

CONCLUSION: This integrative analysis of blood transcriptomes diverged from its initial purpose, the identification of subtype-specific biomarkers, and demonstrated that TLR5 exhibits reproducible diagnostic efficacy for IBD.