Guo Yandong, Pabitra Dahal, Pan Lei, Gong Lanbo, Li Aimin, Liu Side, Xiong Jing
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
BMC Gastroenterol. 2025 Jan 31;25(1):48. doi: 10.1186/s12876-025-03647-y.
Differentiation between ulcerative colitis (UC) and other intestinal inflammatory diseases is difficult, and the precise etiology of UC is poorly understood. Thus, there is a need for novel diagnostic and prognostic biomarkers for UC.
Intestinal mucosal biopsy tissue specimens of inflamed (ulcerative colitis-inflamed, UC-I) and non-inflamed (ulcerative colitis-noninflamed, UC-N) tissue were obtained simultaneously during colonoscopy from newly diagnosed UC patients prior to any treatments. Label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) quantitative proteomics was used to detect proteomic differences between UC-I, UC-N, and normal control subjects (n = 5). Proteins with a fold-change > 1.5 and P < 0.05 between groups were considered to be differentially expressed (DEPs). Candidate biomarkers were further verified in 8 patients of each group by parallel reaction monitoring (PRM) (a prospective cohort, n = 8). Expression of TXNDC5 was quantified using immunohistochemistry (IHC).
A total of 4,788 proteins were identified. Multiple upregulated pathways, including leukocyte trans-endothelial migration and natural killer (NK) cell-mediated cytotoxicity, were identified. Network analysis showed that proteins were involved in 4 pathways in UC-I and 3 pathways in UC-N tissues, and participated in protein-protein interactions. Increased expression of 9 DEPs, including TXNDC5, EPX, and ITGAM were detected in UC patients compared to normal control subjects. Subsequent verification of the 9 DEPs by PRM confirmed the reliability of the mass spectrometry data. TXNDC5 expression was significantly increased in UC.
The pathways, networks, and proteins identified in this study may provide new insights into the molecular pathogenesis of UC. Further studies are required to determine if the proteins identified may help in the diagnosis and treatment of UC.
溃疡性结肠炎（UC）与其他肠道炎症性疾病的鉴别诊断较为困难，且UC的确切病因尚不清楚。因此，需要针对UC的新型诊断和预后生物标志物。
在结肠镜检查期间，从新诊断的未经任何治疗的UC患者中同时获取炎症（溃疡性结肠炎炎症期，UC-I）和非炎症（溃疡性结肠炎非炎症期，UC-N）组织的肠黏膜活检组织标本。采用无标记液相色谱串联质谱（LC-MS/MS）定量蛋白质组学检测UC-I、UC-N和正常对照受试者（n = 5）之间的蛋白质组差异。两组间变化倍数>1.5且P<0.05的蛋白质被认为是差异表达蛋白（DEPs）。通过平行反应监测（PRM）在每组8例患者中进一步验证候选生物标志物（前瞻性队列，n = 8）。使用免疫组织化学（IHC）对TXNDC5的表达进行定量。
共鉴定出4788种蛋白质。鉴定出多个上调的通路，包括白细胞跨内皮迁移和自然杀伤（NK）细胞介导的细胞毒性。网络分析显示，蛋白质参与UC-I组织中的4条通路和UC-N组织中的3条通路，并参与蛋白质-蛋白质相互作用。与正常对照受试者相比，在UC患者中检测到9种DEPs的表达增加，包括TXNDC5、EPX和ITGAM。随后通过PRM对这9种DEPs进行验证证实了质谱数据的可靠性。TXNDC5在UC中的表达显著增加。
本研究中鉴定出的通路、网络和蛋白质可能为UC的分子发病机制提供新的见解。需要进一步研究以确定所鉴定的蛋白质是否有助于UC的诊断和治疗。
