Ganig Nicole, Baenke Franziska, Thepkaysone May-Linn, Lin Kuailu, Rao Venkatesh S, Wong Fang Cheng, Polster Heike, Schneider Martin, Helm Dominic, Pecqueux Mathieu, Seifert Adrian M, Seifert Lena, Weitz Jürgen, Rahbari Nuh N, Kahlert Christoph
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
Cancers (Basel). 2021 Mar 17;13(6):1351. doi: 10.3390/cancers13061351.
The treatment of colorectal cancer (CRC) has improved during the last decades, but methods for crucial early diagnosis are yet to be developed. The influence of the tumour microenvironment on liquid biopsies for early cancer diagnostics are gaining growing interest, especially with emphasis on exosomes (EXO), a subgroup of extracellular vesicles (EVs). In this study, we established paired cancer-associated (CAFs) and normal fibroblasts (NF) from 13 CRC patients and investigated activation status-related protein abundance in derived EXOs. Immunohistochemical staining of matched patient tissue was performed and an independent test cohort of CRC patient plasma-derived EXOs was assessed by ELISA. A total of 11 differentially abundant EV proteins were identified between NFs and CAFs. In plasma EXOs, the CAF-EXO enriched protein EDIL3 was elevated, while the NF-EXO enriched protein QSOX1 was diminished compared to whole plasma. Both markers were significantly reduced in patient-matched CRC tissue compared to healthy colon tissue. In an independent test cohort, a significantly reduced protein abundance of QSOX1 was observed in plasma EXOs from CRC patients compared to controls and diagnostic ROC curve analysis revealed an AUC of 0.904. In conclusion, EXO-associated QSOX1 is a promising novel marker for early diagnosis and non-invasive risk stratification in CRC.
在过去几十年中，结直肠癌（CRC）的治疗方法有所改进，但关键的早期诊断方法仍有待开发。肿瘤微环境对早期癌症诊断的液体活检的影响越来越受到关注，尤其是以外泌体（EXO）为重点，它是细胞外囊泡（EVs）的一个亚组。在本研究中，我们从13例CRC患者中建立了配对的癌症相关成纤维细胞（CAFs）和正常成纤维细胞（NFs），并研究了衍生EXOs中与激活状态相关的蛋白质丰度。对匹配的患者组织进行免疫组织化学染色，并通过ELISA评估CRC患者血浆来源EXOs的独立测试队列。在NFs和CAFs之间共鉴定出11种差异丰富的EV蛋白。在血浆EXOs中，与全血浆相比，CAF-EXO富集的蛋白EDIL3升高，而NF-EXO富集的蛋白QSOX1减少。与健康结肠组织相比，患者匹配的CRC组织中这两种标志物均显著降低。在一个独立的测试队列中，与对照组相比，CRC患者血浆EXOs中QSOX1的蛋白丰度显著降低，诊断ROC曲线分析显示AUC为0.904。总之，EXO相关的QSOX1是CRC早期诊断和非侵入性风险分层的一个有前景的新标志物。
