Author: Claire Hornung

Serum type XII collagen is elevated in patients with solid tumors and is upregulated in cancer associated fibroblasts (CAFs) and normal fibroblasts (NFs) upon TGFb treatment

Introduction

Understanding the tumor microenvironment (TME) and extracellular matrix (ECM) is crucial in cancer research due to their impact on tumor progression. Collagens, major ECM components, regulate cell signaling and behavior, with type XII collagen being particularly vital for ECM organization. This collagen type is often overproduced by cancer-associated fibroblasts (CAFs), and its upregulation has been linked to poor survival outcomes in various cancers. In light of these findings, this study aimed to develop an ELISA for quantifying circulating type XII collagen as a potential cancer biomarker.

Poster

Conclusion

This study unveils a promising avenue for harnessing PRO-C12 as a non-invasive serum biomarker, enabling the quantification of type XII collagen fragments in cancer patients. Further investigations are warranted to explore the potential of PRO-C12 across different cancer types and disease stages, shedding light on its multifaceted role in cancer development.

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The non-invasive fibrosis biomarker measuring type III collagen synthesis (PRO-C3) is elevated in patients with myeloproliferative neoplasms and associate with disease severity and allele burden – lessons learned from the DALIAH trial

Introduction

Myeloproliferative neoplasms (MPNs) are chronic blood cancers characterized by elevated blood cell counts. MPNs arise due to acquired somatic driver mutations in stem cells (JAK2V617F, CALR and MPL) and develop over decades from the earliest stages of essential thrombocythemia (ET) and polycythemia vera (PV) towards advanced primary myelofibrosis (PMF) with bone marrow failure. MPNs are driven by chronic inflammation and characterized by persistent connective tissue remodeling leading to organ
dysfunction due to excessive accumulation of collagens (fibrosis) in the bone marrow. Reduction or stabilization of bone marrow fibrosis is considered a significant therapeutic goal in MPNs, hence monitoring and quantitating fibrosis non-invasively is ideally suited for patients with MPNs.

The aim of this study was to investigate the relevance of non-invasive serological biomarkers of type I collagen synthesis (PRO-C1) and type III collagen synthesis (nordicPRO-C3™) in patients with MPNs.

Poster

Conclusion

The non-invasive fibrosis associated biomarker nordicPRO-C3™, that reflects type III collagen synthesis, is elevated in MPN patients and associate with the severity of the disease and with the JAK2V617F allele burden. NordicPRO-C3™ has potential as a non-invasive bone marrow fibrosis biomarker to stratify and monitor patients with MPNs.

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Variations in fibrotic activity of cancer-associated fibroblasts from different tissues measured using noninvasive, clinically validated biomarkers

Introduction

Cancer-associated fibroblasts (CAFs) are pivotal orchestrators of tumor progression through their modulation of the extracellular matrix (ECM), particularly via the deposition of collagens. Different stimuli (e.g. TGF-β, PDGF-AB, IL-1α) can activate fibroblasts and induce phenotypic alterations in CAFs, promoting a pro-tumorigenic microenvironment characterized by enhanced ECM synthesis and remodeling. Consequently, targeting CAFs and their related pathways presents a promising therapeutic strategy for cancer treatment. However, numerous studies have revealed that CAFs exhibit heterogeneity both within and between individual tissues. Despite this, the specific patterns of collagen deposition by different CAFs remain insufficiently characterized.

In this study, we investigated the fibrotic activity of CAFs from various cancer tissues by measuring the production of three specific collagen peptides in vitro using non-invasive, clinically validated biomarkers.

Poster

Conclusion

These findings underscore the heterogeneity in collagen production and fibrotic activity among CAFs from different indications, providing valuable insights into the ECM dynamics within distinct TMEs.
Collagen-based non-invasive biomarkers demonstrate the capability to differentiate between the fibrotic activity of CAFs isolated from different tissues. In conclusion, this model proves to be a useful tool for anti-fibrotic drug screening.

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Serum biochemical markers of synovial tissue turnover, but not cartilage markers, predict radiological progression in very early rheumatoid arthritis

Introduction

In early rheumatoid arthritis (RA), radiographic assessments are insensitive to identify patients at high risk of progression, because the extension of joint damage, especially cartilage degradation, is rather
limited. Biochemical markers reflecting dynamic processes of tissue remodeling may be more sensitive to predict progression in early RA. To investigate whether soluble markers of matrix-metalloprotease
(MMP) driven type I (C1M) and type II (C2M) collagen degradation as:

1. Indicators of synovial and cartilage tissues remodelling respectively
2. Predict progression of joint damage in a prospective longitudinal
   cohort of patients with early RA.

Poster

Conclusion

Increased baseline serum C1M is consistently associated with a higher risk of radiographic progression in patients with early RA. Synovial tissue remodeling may be a prominent determinant of progression in the early phase of the disease whereas cartilage turnover is likely to play a minor role at this stage.

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Detecting Extracellular Matrix Turnover in axSpA Patients with concomitant Inflammation on MRI and Normal CRP

Introduction

Many patients with axial spondyloarthritis (axSpA) present normal CRP levels despite ongoing inflammation in the axial skeleton. The disease is characterized by hallmark features such as erosions and new bone formation, as well as aberrant neutrophil activation. We hypothesize that mechanistic biomarkers reflecting inflammation directly within the axial skeleton may provide a more accurate assessment of disease activity than CRP.

This study aims to investigate the association between the soluble biomarkers nordicCpa9-HNE™, C3M, and nordicPRO-C3™ and MRI-detected inflammation in the sacroiliac joint (SIJ) and spine of axSpA patients.

Poster

Conclusion

NordicCPa9-HNE™, C3M, and CRP demonstrated significant correlations with spine MRI inflammation at baseline. Notably, CPa9-HNE and C3M exhibited superior sensitivity compared to CRP in detecting spine MRI inflammation at week 52. These findings suggest that nordicCPa9-HNE™ and C3M may serve as valuable biomarkers for monitoring disease activity changes in axial spondyloarthritis (AxSpA) with normal CRP.

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PRO-C3 determined active fibrogenesis is a predictor of liver-related outcomes in patients with chronic hepatitis C

Introduction

Patients with untreated chronic hepatitis C (CHC) infection are at increased risk of developing a liver related outcome. Despite the availability of simplified direct-acting antiviral therapy, the prevalence of CHC remains unchanged in many industrialized countries. Biomarkers that can predict which chronic liver disease patients with inflammatory injury are at greatest risk of developing a clinical outcome are required. In this study we aim to investigate the ability of nordicPRO-C3™ as a marker of active fibrogenesis to predict liver-related outcomes compared to METAVIR fibrosis stage on biopsy in patients with hepatitis C.

Poster

Conclusion

We conclude that fibrosis activity (nordicPRO-C3™) is associated with an increased risk of developing a liver-related outcome in patients with untreated HCV infection. NordicPRO-C3™ provides a higher risk predictor for outcomes than METAVIR fibrosis stage on biopsy. A pro-fibrogenic marker such as nordicPRO-C3™ could provide prognostic utility in other chronic liver disease patients with ongoing inflammatory injury.

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Fibroblast activity kills – Circulating endotrophin (PRO-C6) is prognostic for liver-related events in patients with cirrhosis from chronic hepatitis C

Introduction

Prognostic markers for patients with compensated cirrhosis at increased risk of developing liver-related events are required. Endotrophin, a potential driver of fibroblast activation and mediator of fibroinflammatory disease, may be assessed non-invasively using nordicPRO-C6™. Blood-based collagen extracellular matrix remodeling markers may provide novel prognostic information to identify patients with cirrhosis at higher risk of developing a liver-related event.

In this study we aimed to investigate the ability of nordicPRO-C6™ to predict liver-related events in The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C) (ClinicalTrials.gov #NCT00006164).

Poster

Conclusion

NordicPRO-C6™, a biomarker of circulating endotrophin, was primarily associated with an increased risk of developing a liver-related event in patients with cirrhosis from CHC. NordicPRO-C6™ is a potential monitoring blood-based marker that may also provide prognostic information in treatment-naïve CHC patients with moderate-advanced fibrosis at higher risk of developing a liver-related event. The prognostic utility of nordicPRO-C6™ in CHC patients after sustained virologic response and other advanced stage chronic liver disease is required.

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Endotrophin as an early marker of kidney outcomes in persons with type 2 diabetes: Findings from the PROVALID study

Introduction

Diabetic kidney disease (DKD) is driven by pathophysiological processes, including fibrosis. NordicEndotrophin™ (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has previously been shown to be a biomarker of DKD progression1,2,3,4,5. The aim of this study was to investigate, for the first time, circulating ETP as a risk marker for kidney outcomes in persons with type 2 diabetes (T2D) being taken care of at the primary level of healthcare.

Poster

Conclusion

Plasma ETP (nordicEndotrophin™) has been identified as an independent risk marker for kidney outcomes in individuals with type 2 diabetes (T2D) with early-stage kidney disease. Higher levels of ETP were associated with a significantly increased risk of developing the kidney endpoint in persons with eGFR >90 ml/min/1.73 m2. These findings demonstrate that markers of fibrosis, such as ETP, may serve as early markers for kidney disease progression or kidney failure in persons with T2D and apparently normal kidney function.

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The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI

Introduction

Acute Kidney Injury (AKI), survivors are at increased risk of long-term adverse outcomes, including readmission to hospital. Pathophysiological consequences of AKI, include extracellular matrix (ECM) remodeling. Tools to monitor the long-term health risk of patients after AKI are needed to improve
patient outcome.

Poster

Conclusion

Circulating levels of LG1M were elevated in AKI patients 1 year after the AKI episode and correlated with markers of kidney function in the AKI group and to a lower extent in the CKD control group. In the AKI group, LG1M was associated with the risk of readmission, even though the significance of the association was lost in adjusted analyses. This biomarker, quantifying circulating levels of a laminin fragment, may reflect injury to the basement membrane (of which laminin is a major component) after AKI, which was associated with an increased risk of worse outcome in patients that experienced an episode of AKI.

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Machine-learning classification integrating non-invasive biomarkers, clinical characteristics and pulmonary function

Introduction

Computed tomography (CT) is used for evaluating phenotypic abnormalities in chronic obstructive
pulmonary disease (COPD), yet its cost and time-intensive nature limit routine use. Developing an
easily implementable technique for classifying emphysema extent is thus essential.

This study aimed to develop a diagnostic model to classify emphysema extent in COPD
patients relying solely on easily obtained measures such as clinical characteristics and
non-invasive biomarkers.

Poster

Conclusion

Diagnostic models incorporating easily obtainable measures effectively distinguished COPD patients with high emphysema extent from those with low extent. Such models for classifying emphysema patterns have the potential for clinical implementation, aiding in diagnosis or serving as a decision-making tool to determine the necessity of further CT scans.

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