Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, Punjab, India.
Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141001, Punjab, India.
Dig Liver Dis. 2024 Feb;56(2):258-264. doi: 10.1016/j.dld.2023.09.014. Epub 2023 Oct 8.
Celiac disease (CD) a complex immune disease that affects duodenal mucosa. Identification of tissue specific biomarkers is expected to improve the existing biopsy based CD diagnosis.
To investigate the differentially expressed genes (DEGs) in duodenal mucosa tissue to identify clinically relevant gene expression pattern in CD.
Whole RNA extracted from the duodenal biopsies of three CD patients and four non-CD controls were sequenced. Significant DEGs were identified. Prioritized DEGs were validated using qRT-PCR in an independent group (CD=23; Control=26). Enriched pathways were analyzed, protein-protein interaction networks were evaluated.
923 DEGs comprising of 135 up-regulated, and 788 down-regulated genes, with p-value≤0.05; log2FC>2 or <-2 were identified. A novel down-regulated gene CDH18 (p = 0.03; log2FC=-0.74) was identified. Previously known CXCL9 was replicated. CDH18, a trans-membrane protein was found to interact with other CDH proteins, α/β catenins, and other membrane transporters such as SLC and ABCB. Pathways and protein networks contributing in channel activity (p = 2.15E-12), membrane transporters (p = 2.15E-12), and cellular adhesion (p = 8.05E-6) were identified.
CDH18, a novel DEG identified in the present study is a pivotal gene involved in maintaining epithelial membrane organization and integrity. The functional significance of lower expression of CDH18 in pathogenesis of CD warranted to be investigated. CDH18 expression could be tested for its effectiveness in diagnostic, prognostic and therapeutic purposes.
乳糜泻（CD）是一种影响十二指肠黏膜的复杂免疫性疾病。鉴定组织特异性生物标志物有望改善现有的基于活检的 CD 诊断。
研究十二指肠黏膜组织中的差异表达基因（DEGs），以鉴定 CD 中的临床相关基因表达模式。
从 3 例 CD 患者和 4 例非 CD 对照的十二指肠活检中提取全 RNA，进行测序。鉴定显著差异表达基因。在独立组（CD=23；对照=26）中使用 qRT-PCR 验证优先 DEGs。分析富集途径，评估蛋白质-蛋白质相互作用网络。
共鉴定到 923 个 DEGs，包括 135 个上调基因和 788 个下调基因，p 值≤0.05；log2FC>2 或 <-2。鉴定到一个新的下调基因 CDH18（p=0.03；log2FC=-0.74）。先前已知的 CXCL9 得到了复制。发现跨膜蛋白 CDH18 与其他 CDH 蛋白、α/β 连环蛋白以及 SLC 和 ABCB 等其他膜转运蛋白相互作用。鉴定到参与通道活性（p=2.15E-12）、膜转运体（p=2.15E-12）和细胞黏附（p=8.05E-6）的途径和蛋白质网络。
本研究中鉴定的新的 DEG CDH18 是一个关键基因，参与维持上皮膜组织的结构和完整性。CDH18 低表达在 CD 发病机制中的功能意义值得进一步研究。CDH18 的表达可用于诊断、预后和治疗目的的有效性测试。
