Matrix Metalloprotease Generated Fragments of Type VI Collagen Have Serum Biomarker Potential in Cancer - A Proof of Concept Study.
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
10
01
2019
revised:
12
02
2019
accepted:
14
02
2019
pubmed:
12
3
2019
medline:
12
3
2019
entrez:
12
3
2019
Statut:
ppublish
Résumé
Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activated fibroblast and altered proteolytic degradation by matrix metalloproteases (MMPs). Consequently, pathology-specific COL6 fragments are released to the circulation. This study evaluates four COL6 fragments measured in serum as potential biomarkers for cancer. C6Ma1 (MMP-generated neo-epitope on the a1 chain), C6Ma3 (MMP-generated neo-epitope on the a3 chain), PRO-C6 (C-terminal of the a3 chain) and IC-6 (internal epitope on the a1 chain) were measured by ELISA in serum from patients with various stage 1-4 cancer indications (n = 4-11 per indication, total n = 65) and healthy controls (n = 13). C6Ma1 and C6Ma3 were significantly elevated in most cancer types compared to controls; PRO-C6 and IC6 were not. No significant differences were seen according to age, gender and TNM stage. Comparing cancer patients to controls, the AUROC was 0.90 (P < .0001), 0.87 (P < .0001), 0.59 (P = .311) and 0.53 (P = .747) for C6Ma1, C6Ma3, PRO-C6 and IC-6, respectively. Only C6M and C6Ma3 correlated significantly (Spearman, r = 0.74, P < .0001). MMP-generated COL6 fragments (C6Ma1, C6Ma3) were elevated in serum from cancer patients compared to controls and had promising diagnostic accuracy. This supports that MMP-mediated COL6 remodeling is important in tumorigenesis and indicate cancer biomarker potential of quantifying COL-6 fragments in serum. Future studies should determine biological and clinical applicability of the COL-6 serum biomarkers in relation to cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activated fibroblast and altered proteolytic degradation by matrix metalloproteases (MMPs). Consequently, pathology-specific COL6 fragments are released to the circulation. This study evaluates four COL6 fragments measured in serum as potential biomarkers for cancer.
METHODS
METHODS
C6Ma1 (MMP-generated neo-epitope on the a1 chain), C6Ma3 (MMP-generated neo-epitope on the a3 chain), PRO-C6 (C-terminal of the a3 chain) and IC-6 (internal epitope on the a1 chain) were measured by ELISA in serum from patients with various stage 1-4 cancer indications (n = 4-11 per indication, total n = 65) and healthy controls (n = 13).
RESULTS
RESULTS
C6Ma1 and C6Ma3 were significantly elevated in most cancer types compared to controls; PRO-C6 and IC6 were not. No significant differences were seen according to age, gender and TNM stage. Comparing cancer patients to controls, the AUROC was 0.90 (P < .0001), 0.87 (P < .0001), 0.59 (P = .311) and 0.53 (P = .747) for C6Ma1, C6Ma3, PRO-C6 and IC-6, respectively. Only C6M and C6Ma3 correlated significantly (Spearman, r = 0.74, P < .0001).
CONCLUSIONS
CONCLUSIONS
MMP-generated COL6 fragments (C6Ma1, C6Ma3) were elevated in serum from cancer patients compared to controls and had promising diagnostic accuracy. This supports that MMP-mediated COL6 remodeling is important in tumorigenesis and indicate cancer biomarker potential of quantifying COL-6 fragments in serum. Future studies should determine biological and clinical applicability of the COL-6 serum biomarkers in relation to cancer.
Identifiants
pubmed: 30856553
pii: S1936-5233(19)30014-2
doi: 10.1016/j.tranon.2019.02.004
pmc: PMC6411605
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
693-698Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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