Type IV collagen as a tumour marker for colorectal liver metastases

Nyström, Hanna; Naredi, Peter; Hafström, Larsolof; Sund, Malin

doi:10.1016/j.ejso.2011.04.010

Cited by 36 publications

(46 citation statements)

References 29 publications

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“…This finding was unexpected as other studies had shown increased progression and poor survival in cases with high type IV collagen tissue expression (16,17,30). Our data were the result of a blinded evaluation of the type IV collagen expression.…”

Section: Nonmalignant Epithelium Invasive Frontcontrasting

confidence: 48%

“…Indeed, type IV collagen has been found to correlate to disease activity as removal of colorectal liver metastases lead to a decrease in the serum type IV collagen concentration. In addition, recurrence of disease was associated with an increase in the type IV collagen concentration (16).…”

Section: Nonmalignant Epithelium Invasive Frontmentioning

confidence: 99%

“…BIO82) was used for determination of circulating type IV collagen fragments (a1-chain fragments), which for the remainder of this paper will be referred to just as type IV collagen. The ELISA had been developed and validated for measurements of serum samples, and have been used in previously published studies (15)(16)(17)(27)(28)(29). Prior to use, we validated the assay for use of citrated plasma samples (Supplementary Data, Appendix S2).…”

Section: Type IV Collagen Determinationsmentioning

confidence: 99%

“…Each a-chain consists of an amino terminal 7S-domain, a long central triple-helical region and a carboxy-terminal noncollagenous domain-NC1 domain (14). An increase in the levels of circulating type IV collagen fragments were reported to be associated with the presence of malignant disease in patients with breast cancer (15), presence of liver metastases in colorectal cancer (16), and to be associated with poor prognosis in patients with pancreatic cancer (17). The proposed mechanism for the increase in circulating type IV collagen concentration was tumor-induced tissue remodeling through desmoplasia and proteolysis (17).…”

Section: Introductionmentioning

confidence: 99%

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The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Rolff

Christensen

Vainer

et al. 2016

Clinical Cancer Research

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Purpose: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer.Experimental Design: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries.Results: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78-2.84; P < 0.0001] and 2.24 (95% CI, 1.75-2.86; P < 0.0001) for the training and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving and not receiving adjuvant antineoplastic therapy. However, in the validation set, the prognostic effect of the marker vanished when looking at patients who received adjuvant antineoplatic therapy (HR 0.90; 95% CI, 0.42-1.93) but was still present in the group not receiving adjuvant chemotherapy (HR 2.88; 95% CI, 1.98-4.21).Conclusions: The results indicate clinical validity of type IV collagen as a prognostic biomarker in colorectal cancer, although the suggested predictive role of the marker should be validated.

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Section: Nonmalignant Epithelium Invasive Frontcontrasting

confidence: 48%

Section: Nonmalignant Epithelium Invasive Frontmentioning

confidence: 99%

Section: Type IV Collagen Determinationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Rolff

Christensen

Vainer

et al. 2016

Clinical Cancer Research

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“…Elevated levels of circulating fragments of collagen type I, III and IV have been associated with different cancer types, including head and neck cancer [17], breast cancer [18,19], liver cancer [20], colorectal liver metastases [21] and for the hepatic failure following liver resection for hepatocellular carcinoma [22]. This indicates that collagen degradation and release of fragments to the circulation is an ongoing event in many types of cancer, and that collagen degradation markers may be applicable to disease monitoring in several cancer types.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix specific protein fingerprints measured in serum can separate pancreatic cancer patients from healthy controls

et al. 2013

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BackgroundPancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specific MMP-generated collagen fragments differentiate PC patients from healthy controls when measured in serum.MethodsThe levels of biomarkers reflecting MMP-mediated degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12a1) collagen were assessed in serum samples from PC patients (n = 15) and healthy controls (n = 33) using well-characterized and validated competitive ELISAs.ResultsThe MMP-generated collagen fragments were significantly elevated in serum from PC patients as compared to controls. The diagnostic power of C1M, C3M, C4M and C4M12 were ≥83% (p < 0.001) and when combining all biomarkers 99% (p < 0.0001).ConclusionsA panel of serum biomarkers reflecting altered MMP-mediated collagen turnover is able to differentiate PC patients from healthy controls. These markers may increase the understanding of mode of action of the disease and, if validated in larger clinical studies, provide an improved and additional tool in the PC setting.

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Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study

Nordholm-Carstensen

Krarup

Morton

et al. 2015

Intl Journal of Cancer

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The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic-and Cox-regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR) 5 0.54 (95% confidence interval (

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Type IV collagen as a tumour marker for colorectal liver metastases

Abstract: Type IV collagen has the potential to be used as tumour associated biomarker for CLM. These results indicate the importance of interaction between cancer cells and the stroma in the tumour microenvironment.

Cited by 36 publications

References 29 publications

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer: A Retrospective Multicenter Study

Extracellular matrix specific protein fingerprints measured in serum can separate pancreatic cancer patients from healthy controls

Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study

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