Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer.

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS Clinical proteomics Pub Date : 2024-10-09 DOI:10.1186/s12014-024-09510-8

Zhaoyue Zhong, Jiayin Ji, Hongxia Li, Ling Kang, Haipeng Zhu

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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转移性结直肠癌患者血浆外泌体的蛋白质组学分析。

背景：结直肠癌（CRC），尤其是转移性结直肠癌（mCRC）的诊断和治疗是一项重大的优先事项和研究挑战。我们筛选了mCRC患者、CRC患者和健康对照组（HCs）血浆外泌体蛋白质组的表达差异，以发现mCRC的潜在生物标记物：方法：收集五名mCRC患者、五名CRC患者和五名健康对照者的血浆样本，并通过超速离心法分离外泌体。使用BCA试剂盒测定外泌体蛋白质浓度，并利用液相色谱-质谱法鉴定和分析蛋白质：结果：从血浆样本中分离出的外泌体共检测到994种可定量的蛋白质，其中包括287种通过定量蛋白质组学分析确定的差异表达蛋白质。在 mCRC 患者、CRC 患者和 HCs 中分别发现了 965、963 和 968 个蛋白质。研究在 mCRC 患者的血浆外泌体中发现了 83 个表达不同的蛋白质。mCRC组和CRC组中前十名上调的蛋白质分别是ITGA4、GNAI1、SFTPA2、UGGT1、GRN、LBP、SMIM1、BMP1、HMGN5和MFAP4，而前十名下调的蛋白质分别是PSMB8、LCK、RAB35、PSMB4、CD81、CD63、GLIPR2、RAP1B、RAB30和CES1。Western Blot验证数据证实，ITGA4和GNAI1明确富集在mCRC患者的血浆外泌体中：这些差异蛋白为进一步研究 mCRC 的发病机制和确定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了解和治疗 mCRC 的潜在意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical proteomics BIOCHEMICAL RESEARCH METHODS-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

17 weeks

期刊介绍： Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.