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Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF., Methods: Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not., Results: Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics., Conclusion: Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF., (© 2021. The Author(s).)

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and isomerization. Each PTM results from a specific local physiological or pathobiological process. Identification of each modification to a tissue-specific protein may reveal a unique disease-specific biochemical marker. During cancer metastasis, the host tissue is extensively degraded and replaced by cancer-associated extracellular matrix (ECM) proteins. Furthermore, severe cellular stress and inflammation, caused by cancer, results in generation of PTMs, which will be distributed throughout the ECM. This gives rise to release of protein-specific fragments to the circulation. Here we highlight the importance of remodeling of the ECM in cancer and the generation of PTMs, which may be cancer specific and reflect disease progression; thus having potential for biochemical marker development.

Summary: Background: Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. Aim: To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis. Methods: Serum samples were available from 138 large‐duct primary sclerosing cholangitis patients (of which 102 [74%] with IBD) recruited 2008‐2012 and 52 ulcerative colitis patients (controls). The median follow‐up time was 2.2 (range 0‐4.3) years. Specific biomarkers of type III and V collagen formation (PRO‐C3 and PRO‐C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N‐terminal peptide, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid was assessed for comparison. Results: All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P < 0.001). PRO‐C3 showed the largest difference between the two groups with a threefold increase in primary sclerosing cholangitis compared to ulcerative colitis patients. Patients with high baseline serum levels of all markers, except C3M, had shorter survival compared to patients with low baseline serum levels (P < 0.001). Combining PRO‐C3 and PRO‐C5 the odds ratio for predicting transplant‐free survival was 47 compared to the Enhanced Liver Fibrosis test's odds ratio of 11. Conclusions: Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO‐C3 was identified as a potent prognostic marker and an independent predictor of transplant‐free survival in primary sclerosing cholangitis. [ABSTRACT FROM AUTHOR]

Background Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estimate dynamics of fibrosis, regression or progression, in response to therapy. Aim One of the most pressing needs in modern clinical chemistry for fibroproliferative disorders is the development of biomarkers for early diagnosis, prognosis, and early efficacy for the benefit of patients and to facilitate improved drug development. The aim of this article was to review the serological biomarkers that may assist in early diagnosis of patients, separate fast from slow- or nonprogressors, and possibly assist in drug development for fibroproliferative diseases, exemplified by liver fibrosis. The lack of success of biochemical markers and the possible reasons for this is discussed in the context of other fields with biomarker success. Method This is a personal opinion review article. Results Biochemical markers, originating from the fibrotic structure, may have increased specificity and sensitivity for disease. Assessment of the tissue turnover balance by measurement of tissue formation and tissue degradation separately by novel technologies may provide value. Conclusions Novel technologies focused on the protein fingerprint in addition to biomarker classification, may increase the quality of biomarker development and provide the much needed biomarkers to further the fibroproliferative field. This is in direct alignment with the Food and Drug Administration and European Medicinal Agencies initiatives of personal health care. [ABSTRACT FROM AUTHOR]

Aim: To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression. Methods: Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230). An assay developed using the biotin-streptavidin system was evaluated in a rat reversible model of fibrosis. Animals were treated for duration of 4, 6 and 8 weeks. Animals that were treated for 8 weeks were left to regress for a period of 14, 20 and 26 weeks. Results: Mean CO5-1230 level for control animals was found to be 8.7 ng/mL. CO5-1230 marker levels, at termination points, for CCl4 treated animals was be 8.7 ng/mL at 4 weeks (P < 0.05, ROC: 0.83), 11.4 ng/mL at 6 weeks (P < 0.001, ROC: 0.93) and 10.8 ng/mL at 8 weeks (P < 0.05, ROC: 0.82). During regression phase, marker levels were statistically significantly decreased when compared with the marker levels at 8 weeks of treatment. Marker levels were found to be 5.9 ng/mL (P < 0.001, ROC: 0.8) after 14 weeks of regression, 3.9 ng/mL (P < 0.001, ROC: 0.95) after 20 weeks and 4.5 ng/mL (P < 0.001, ROC: 0.97) after 26 weeks of regression. Conclusions: The data indicates that CO5-1230 levels are statistically significantly increased when CCl4 intoxication stimulus is applied in all treatment time points. CO5-1230 levels return back to control levels when the stimulus is removed. The above finding adds to our previous evaluation of the marker and suggests that CO5-1230 may be a promising potential marker for liver fibrosis staging and monitoring in both disease progression and regression. [ABSTRACT FROM AUTHOR]