Proteomic Analyses of Fibroblast- and Serum-Derived Exosomes Identify QSOX1 as a Marker for Non-invasive Detection of Colorectal Cancer.

cancer-associated fibroblasts colorectal cancer exosomes extracellular vesicles liquid biopsy tumour microenvironment

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
17 Mar 2021
Historique:
received: 25 01 2021
revised: 12 03 2021
accepted: 13 03 2021
entrez: 3 4 2021
pubmed: 4 4 2021
medline: 4 4 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33802764
pii: cancers13061351
doi: 10.3390/cancers13061351
pmc: PMC8002505
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Deutsche Krebshilfe
ID : KA 3511/3-1
Organisme : Deutschen Konsortium für Translationale Krebsforschung
ID : JF DKTK Surgery
Organisme : Roland Ernst Stiftung
ID : 5/15

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Auteurs

Nicole Ganig (N)

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.

Franziska Baenke (F)

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.

May-Linn Thepkaysone (ML)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Kuailu Lin (K)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Venkatesh S Rao (VS)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Fang Cheng Wong (FC)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Heike Polster (H)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Martin Schneider (M)

MS-based Protein Analysis Unit, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.

Dominic Helm (D)

MS-based Protein Analysis Unit, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.

Mathieu Pecqueux (M)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Adrian M Seifert (AM)

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.
National Center for Tumor Diseases (NCT), Partner Site Dresden, D-69120 Heidelberg, Germany.

Lena Seifert (L)

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.
National Center for Tumor Diseases (NCT), Partner Site Dresden, D-69120 Heidelberg, Germany.

Jürgen Weitz (J)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.

Nuh N Rahbari (NN)

Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, D-68167 Mannheim, Germany.

Christoph Kahlert (C)

Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
National Center for Tumor Diseases (NCT), Partner Site Dresden, D-69120 Heidelberg, Germany.

Classifications MeSH