serum exosomes contain SPARC and LRG1 as biomarkers for colon cancer and differ by tumor primary location

Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.

研究目的：近年来，左右侧结肠癌的分型差异逐渐受到学界关注。肿瘤位于右侧与较差的总生存期（overall survival）及无进展生存期（progression-free survival）显著相关。本研究旨在通过定量蛋白质组学（quantitative proteomics）技术，系统分析左右侧结肠癌来源外泌体（exosomes）的表达多样性。
实验设计：本研究分别从左右侧结肠癌患者与健康志愿者体内分离外泌体，用血清来源外泌体（serum-derived exosomes）处理结直肠癌细胞系；随后分别对血清来源外泌体以及经外泌体处理的结直肠癌细胞系开展定量蛋白质组学分析。
实验结果：右侧结肠癌患者血清外泌体蛋白质组的表达谱与左侧结肠癌患者存在显著差异。右侧结肠癌来源的血清外泌体可通过上调细胞外基质相关蛋白，尤其是SPARC这类蛋白聚糖（proteoglycans）及LRG1这类糖蛋白（glycoprotein），促进肿瘤转移。外泌体SPARC与LRG1的表达水平与无进展生存期密切相关。
研究结论：蛋白质组学分析结果显示，左右侧结肠癌的外泌体蛋白质谱存在显著差异。右侧结肠癌来源的血清外泌体可通过高表达SPARC与LRG1，进而促进肿瘤转移。