@article {246821,
	title = {RNA methylation machinery and mA target genes as circulating biomarkers of ulcerative colitis and Crohn{\textquoteright}s disease: Correlation with disease activity, location, and inflammatory cytokines.},
	journal = {Clinica chimica acta; international journal of clinical chemistry},
	volume = {561},
	year = {2024},
	pages = {119831},
	abstract = {<p>Accurate diagnosis of ulcerative colitis (UC) and Crohn{\textquoteright}s disease (CD), the main subtypes of inflammatory bowel disease (IBD), has been challenging due to the constraints of the current techniques. N-methyl adenosine (mA) regulators have evolved as key players in IBD pathogenesis; however, their relation to its clinical setting is largely unexplored. This study investigated the potential of selected RNA methylation machinery and mA target genes as serum biomarkers of UC and CD, their predictive and discriminating capabilities, and their correlations with laboratory data, interleukin (IL)-6, interferon-γ, disease activity scores, and pathological features. Fifty UC and 45 CD patients, along with 30 healthy volunteers were enlisted. The mRNA expression levels of the mA writers methyltransferase-like 3 (METTL3) and Wilms-tumor associated protein (WTAP), and the reader YTH domain family, member 1 (YTHDF1), along with the mA candidate genes sex determining region Y-box 2 (SOX2), hexokinase 2 (HK2), and ubiquitin-conjugating enzyme E2 L3 (UBE2L3) were upregulated in UC patients, whereas only METTL3, HK2, and UBE2L3 were upregulated in CD patients versus controls. Serum WTAP (AUC~=~0.94, 95~\%CI~=~0.874-1.006) and HK2 (AUC~=~0.911, 95~\%CI~=~0.843-0.980) expression levels showed excellent diagnostic accuracy for UC, METTL3 showed excellent diagnostic accuracy for CD (AUC~=~0.91, 95~\%CI~=~0.828-0.992), meanwhile, WTAP showed excellent discriminative power between the two diseases (AUC~=~0.91, 95~\%CI~=~0.849-0.979). Multivariate logistic analysis unveiled the association of METTL3 and UBE2L3 expression with the risk of CD and UC diagnosis, respectively, controlled by age and sex as confounders. Remarkable correlations were recorded between the gene expression of studied mA regulators and targets in both diseases. Among UC patients, serum METTL3 and WTAP were correlated with UC extent/type, while WTAP was correlated with IL-6. Among CD patients, serum METTL3 and HK2 were correlated with CD activity index (CDAI) and CD location. In conclusion, mA regulators and target genes are distinctly expressed in UC and CD clinical samples, correlate with disease activity and extent/location, and could serve as a novel approach to empower the diagnosis and stratification of IBD subtypes.</p>
},
	author = {Tarek K. Motawi and Olfat G Shaker and Amr, Ghada and Mahmoud A Senousy}
}
