结直肠癌（CRC），特别是转移性结直肠癌（mCRC）的诊断和治疗是一个主要优先事项和研究挑战。我们筛选了 mCRC 患者、CRC 患者和健康对照 (HC) 血浆外泌体蛋白质组的表达差异，以发现 mCRC 的潜在生物标志物。收集了 5 名 mCRC 患者、5 名 CRC 患者和 5 名 HC 的血浆样本并通过超速离心处理分离外泌体。采用BCA试剂盒测定外泌体蛋白浓度，并采用液相色谱-质谱联用技术对蛋白进行鉴定和分析。从血浆样品分离的外泌体中，共检测到994个可定量蛋白，其中定量鉴定出287个差异表达蛋白。蛋白质组学分析。在 mCRC 患者、CRC 患者和 HC 中分别鉴定出总共 965、963 和 968 个蛋白质。该研究鉴定出转移性结直肠癌患者血浆外泌体中存在差异表达的 83 种蛋白质。 mCRC组和CRC组上调前10位的蛋白为ITGA4、GNAI1、SFTPA2、UGGT1、GRN、LBP、SMIM1、BMP1、HMGN5、MFAP4，下调前10位的蛋白为PSMB8、LCK、RAB35、PSMB4、CD81 、CD63、GLIPR2、RAP1B、RAB30 和 CES1。 Western Blot 验证数据证实，ITGA4 和 GNAI1 在 mCRC 患者血浆来源的外泌体中明确富集。这些差异蛋白为进一步研究 mCRC 发病机制和识别治疗靶点提供了潜在的新候选分子。这项研究揭示了血浆外泌体蛋白质组学研究对我们理解和治疗 mCRC 的潜在意义。© 2024。作者。

The diagnosis and treatment of colorectal cancer (CRC), especially metastatic colorectal cancer (mCRC), is a major priority and research challenge. We screened for expression differences in the plasma exosomal proteomes of patients with mCRC, those with CRC, and healthy controls (HCs) to discover potential biomarkers for mCRC.Plasma samples from five patients with mCRC, five patients with CRC, and five HCs were collected and processed to isolate exosomes by ultracentrifugation. Exosomal protein concentrations were determined using the BCA kit, and liquid chromatography-mass spectrometry was utilized to identify and analyze the proteins.From the exosomes isolated from plasma samples, a total of 994 quantifiable proteins were detected, including 287 differentially expressed proteins identified by quantitative proteomics analyses. Totals of 965, 963 and 968 proteins were identified in mCRC patients, CRC patients, and HCs, respectively. The study identified 83 proteins with differential expression in the plasma exosomes of mCRC patients. The top 10 upregulated proteins in the mCRC group and CRC groups were ITGA4, GNAI1, SFTPA2, UGGT1, GRN, LBP, SMIM1, BMP1, HMGN5, and MFAP4, while the top 10 downregulated proteins were PSMB8, LCK, RAB35, PSMB4, CD81, CD63, GLIPR2, RAP1B, RAB30, and CES1. Western Blot validation data confirmed that ITGA4 and GNAI1 were unequivocally enriched in plasma-derived exosomes from mCRC patients.These differential proteins offer potential new candidate molecules for further research on the pathogenesis of mCRC and the identification of therapeutic targets. This study sheds light on the potential significance of plasma exosome proteomics studies in our understanding and treatment of mCRC.© 2024. The Author(s).