Crohn’s disease (CD) is a nonspecific inflammatory disease of digestive tract with limited known biomarkers. We aimed to identify potential molecules involved in CD severity. Weighted gene co-expression network and differentially expressed gene analyses were used to explore hub genes associated with inflammation and involved in pathological processes of CD in the GSE83448 cohort. The expression and relationship of genes with clinical characteristics in normal and CD intestinal mucosa were validated in GSE208303 and our research cohorts. Five genes related to disease and inflammation were identified in the clinically significant modules that were differentially expressed in healthy controls and CD patients. Among them, solute carrier family 39 member 5 (SLC39A5) expression was reduced in CD tissues compared with that in normal tissues; low SLC39A5 expression was associated with CD-simplifying endoscopic score and stenosis. Furthermore, we broadened the bioinformatic threshold with qRT-PCR verification and western blot, and found that the expressions of cytochrome P450 family 2 subfamily S member 1 (CYP2S1), fatty acid 2-hydroxylase (FA2H), fatty acid binding protein 1 (FABP1), and Rho family GTPase 3 (RND3) were reduced in CD tissues. Therefore, SLC39A5, CYP2S1, FA2H, FABP1, and RND3 may be novel biomarkers for CD and associated with severity.

Highlights

1. SLC39A5 expression was reduced in CD tissues.

2. Low SLC39A5 expression was associated with CD-simplifying endoscopic score and stenosis.

3. CYP2S1, FA2H, FABP1, and RND3 were reduced in CD tissues.

克罗恩病（CD）是一种消化道非特异性炎症性疾病，已知的生物标志物有限。我们的目的是确定与 CD 严重程度相关的潜在分子。使用加权基因共表达网络和差异表达基因分析来探索 GSE83448 队列中与炎症相关并参与 CD 病理过程的中枢基因。GSE208303 和我们的研究队列验证了正常和 CD 肠粘膜中基因的表达及其与临床特征的关系。在具有临床意义的模块中鉴定出与疾病和炎症相关的五个基因，这些基因在健康对照和 CD 患者中存在差异表达。他们之中，与正常组织相比，CD组织中溶质载体家族39成员5（SLC39A5）表达减少；SLC39A5 低表达与 CD 简化内镜评分和狭窄相关。此外，我们通过qRT-PCR验证和蛋白质印迹拓宽了生物信息学阈值，发现细胞色素P450家族2亚家族S成员1（CYP2S1）、脂肪酸2-羟化酶（FA2H）、脂肪酸结合蛋白1（FABP1）的表达) 和 Rho 家族 GTPase 3 (RND3) 在 CD 组织中减少。因此，SLC39A5、CYP2S1、FA2H、FABP1 和 RND3 可能是 CD 的新型生物标志物，并且与严重程度相关。并发现 CD 组织中细胞色素 P450 家族 2 亚家族 S 成员 1 (CYP2S1)、脂肪酸 2-羟化酶 (FA2H)、脂肪酸结合蛋白 1 (FABP1) 和 Rho 家族 GTPase 3 (RND3) 的表达减少。因此，SLC39A5、CYP2S1、FA2H、FABP1 和 RND3 可能是 CD 的新型生物标志物，并且与严重程度相关。并发现 CD 组织中细胞色素 P450 家族 2 亚家族 S 成员 1 (CYP2S1)、脂肪酸 2-羟化酶 (FA2H)、脂肪酸结合蛋白 1 (FABP1) 和 Rho 家族 GTPase 3 (RND3) 的表达减少。因此，SLC39A5、CYP2S1、FA2H、FABP1 和 RND3 可能是 CD 的新型生物标志物，并且与严重程度相关。

强调

1. CD 组织中 SLC39A5 表达减少。

2. SLC39A5 低表达与 CD 简化内镜评分和狭窄相关。

3. CD 组织中 CYP2S1、FA2H、FABP1 和 RND3 减少。