Xiao Chong, Wu Hao, Long Jing, You Fengming, Li Xueke
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China.
Oncology Teaching and Research Department, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China.
J Proteome Res. 2025 Feb 7;24(2):599-611. doi: 10.1021/acs.jproteome.4c00728. Epub 2025 Jan 5.
Comprehensive protein profiling in intestinal tissues provides detailed information about the pathogenesis of colorectal cancer (CRC). This study quantified the expression levels of 92 oncology-related proteins in tumors, paired para-carcinoma tissues, and remote normal tissues from a cohort of 52 CRC patients utilizing the Olink technology. The proteomic profile of normal tissues closely resembled that of para-carcinoma tissues while distinctly differing from that of tumors. Among the 68 differentially expressed proteins (DEPs) identified between the tumor and normal tissues, WISP-1, ESM-1, and TFPI-2 showed the most pronounced alterations and exhibited relatively strong correlations. These markers also presented the highest AUC values for distinguishing between tissue types. Bioinformatic analysis of the DEPs revealed that the plasma membrane and the PI3K-AKT signaling pathway were among the most enriched GO terms and KEGG pathways. Furthermore, although TFPI-2 is typically recognized as a tumor suppressor, both Olink and enzyme linked immunosorbent assay (ELISA) analyses have demonstrated that its expression is significantly elevated in tumors compared with paired normal tissues. To the best of our knowledge, this is the first study to profile the proteome of intestinal tissue using the Olink technology. This work offers valuable insights into potential biomarkers and therapeutic targets for CRC, complementing the Olink profiling of circulating proteins.
肠道组织中的综合蛋白质谱分析为结直肠癌（CRC）的发病机制提供了详细信息。本研究利用Olink技术对52例CRC患者队列的肿瘤组织、配对癌旁组织和远端正常组织中92种肿瘤相关蛋白的表达水平进行了定量分析。正常组织的蛋白质组学特征与癌旁组织非常相似，而与肿瘤组织明显不同。在肿瘤组织和正常组织之间鉴定出的68种差异表达蛋白（DEP）中，WISP-1、ESM-1和TFPI-2表现出最显著的变化，并呈现出相对较强的相关性。这些标志物在区分组织类型方面也呈现出最高的AUC值。对DEP的生物信息学分析表明，质膜和PI3K-AKT信号通路是最富集的GO术语和KEGG通路之一。此外，尽管TFPI-2通常被认为是一种肿瘤抑制因子，但Olink和酶联免疫吸附测定（ELISA）分析均表明，与配对的正常组织相比，其在肿瘤中的表达显著升高。据我们所知，这是第一项使用Olink技术对肠道组织蛋白质组进行分析的研究。这项工作为CRC的潜在生物标志物和治疗靶点提供了有价值的见解，补充了循环蛋白的Olink分析。
