溃疡性结肠炎(UC)和克罗恩病(CD)的准确诊断,炎症性肠病(IBD)的主要亚型,由于当前技术的限制,一直具有挑战性。N6-甲基腺苷(m6A)调节因子已发展成为IBD发病机制的关键参与者;然而,它们与其临床环境的关系在很大程度上是未经探索的。本研究调查了选定的RNA甲基化机制和m6A靶基因作为UC和CD血清生物标志物的潜力。他们的预测和辨别能力,以及它们与实验室数据的相关性,白细胞介素(IL)-6,干扰素-γ,疾病活动评分,和病理特征。50名UC和45CD患者,以及30名健康志愿者被招募。m6Awriters甲基转移酶样3(METTL3)和Wilms肿瘤相关蛋白(WTAP)的mRNA表达水平,和读者YTH域家族,成员1(YTHDF1),与m6A候选基因性别决定区Y-box2(SOX2)一起,己糖激酶2(HK2),和泛素结合酶E2L3(UBE2L3)在UC患者中上调,而与对照组相比,CD患者中只有METTL3,HK2和UBE2L3上调.血清WTAP(AUC=0.94,95CI=0.874-1.006)和HK2(AUC=0.911,95CI=0.843-0.980)表达水平对UC具有出色的诊断准确性,METTL3对CD具有出色的诊断准确性(AUC=0.91,95CI=0.828-0.992),同时,WTAP在两种疾病之间显示出良好的区分能力(AUC=0.91,95CI=0.849-0.979)。多因素logistic分析揭示了METTL3和UBE2L3表达与CD和UC诊断风险的相关性。分别,由年龄和性别作为混杂因素控制。在两种疾病中,所研究的m6A调节因子的基因表达与靶标之间记录了显着的相关性。在UC患者中,血清METTL3和WTAP与UC程度/类型相关,WTAP与IL-6相关。在CD患者中,血清METTL3和HK2与CDAI和CD位置相关。总之,m6A调节因子和靶基因在UC和CD临床样本中明显表达,与疾病活动和程度/位置相关,并且可以作为一种新的方法来授权IBD亚型的诊断和分层。
Accurate diagnosis of ulcerative colitis (UC) and Crohn\'s disease (CD), the main subtypes of inflammatory bowel disease (IBD), has been challenging due to the constraints of the current techniques. N6-methyl adenosine (m6A) 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 m6A 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 45CD patients, along with 30 healthy volunteers were enlisted. The mRNA expression levels of the m6A writers methyltransferase-like 3 (METTL3) and Wilms-tumor associated protein (
WTAP), and the reader YTH domain family, member 1 (YTHDF1), along with the m6A 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 m6A 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 CDAI and CD location. In conclusion, m6A 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.