Circulating extracellular matrix biomarkers in the detection of carcinoid heart disease
5 affiliations
- 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- 2ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark
- 3Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- 4Nordic Bioscience A/S, Herlev, Denmark
- 5Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
Abstract
Objective: Carcinoid heart disease (CHD) is a severe fibrotic complication affecting cardiac valves in patients with neuroendocrine neoplasms (NENs). Early detection is crucial to improve prognosis. The value of the recommended screening biomarker, NT-proBNP, is uncertain. Biomarkers reflecting extracellular matrix (ECM) remodeling may capture early fibrogenesis. We aimed to evaluate circulating ECM biomarkers for the detection of CHD and to compare their performance with NT-proBNP.
Design and methods: In this cross-sectional study, we prospectively included patients with disseminated small intestinal NENs (siNENs). We performed transthoracic echocardiography (TTE) for CHD diagnosis, and blood samples were analyzed for 10 ECM biomarkers. Biomarker levels were compared between patients with and without CHD, and diagnostic performance was assessed using the area under the receiver operating characteristic (AUROC) curve.
Results: Among 98 patients, 16 (16%) had CHD. PRO-C3 levels were significantly elevated in patients with CHD compared with patients without CHD (median: 19.3 ng/mL (IQR: 15.6–24.0) vs 14.3 ng/mL (IQR: 12.4–17.5), P = 0.002). The AUROC curve of PRO-C3 for CHD detection was 0.77 (95% CI: 0.64–0.90). At a cutoff level of 15.4 ng/mL, the sensitivity was 85%, the specificity was 56%, the positive predictive value was 27%, and the negative predictive value was 95%. In the direct comparison between PRO-C3 and NT-proBNP, PRO-C3 did not outperform NT-proBNP (P = 0.09).
Conclusion: PRO-C3, reflecting collagen type III formation, demonstrated good performance in CHD detection and may represent a complementary or potentially earlier marker than NT-proBNP. However, the performance of PRO-C3 was insufficient as a stand-alone tool, and further evaluation and exploration of new biomarkers in larger cohorts is required.
Related
- Epicardial adipose tissue thickness is associated with circulating biomarkers in individuals without known cardiac disease across a broad adiposity spectrum
- Short-Term Changes in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Related Circulating Biomarkers Following a Very-Low Calorie Ketogenic Diet (VLCKD): A Paired Longitudinal Analysis
- Circulating biomarkers reflect distinct quantitative CT-defined features of systemic sclerosis-associated interstitial lung disease
- Lipidomic Profiling of Peripheral Extracellular Vesicles as a Potential Source of Biomarkers in Gaucher Disease
- Advanced Carcinoid Tricuspid Valve Disease Associated with Delayed Recognition and Loss of the Interventional Window in a Patient with Ileal Neuroendocrine Tumor: A Case Report
BibTeX
@article{lau2026circulating,
title = {{Circulating extracellular matrix biomarkers in the detection of carcinoid heart disease}},
author = {Tobias Stemann Lau and Elisavet Angeli and Riina Karoliina Oksjoki and Vibeke Guldbrand Rasmussen and Federica Genovese and Linda Skibsted Kornerup and Henning Grønbæk and Gitte Dam},
journal = {Endocrine Oncology},
year = {2026},
month = oct,
doi = {10.1530/eo-26-0059},
url = {https://doi.org/10.1530/eo-26-0059},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Circulating extracellular matrix biomarkers in the detection of carcinoid heart disease
AU - Tobias Stemann Lau
AU - Elisavet Angeli
AU - Riina Karoliina Oksjoki
AU - Vibeke Guldbrand Rasmussen
AU - Federica Genovese
AU - Linda Skibsted Kornerup
AU - Henning Grønbæk
AU - Gitte Dam
PY - 2026
DA - 2026/10/26
JO - Endocrine Oncology
DO - 10.1530/eo-26-0059
UR - https://doi.org/10.1530/eo-26-0059
AB - Objective: Carcinoid heart disease (CHD) is a severe fibrotic complication affecting cardiac valves in patients with neuroendocrine neoplasms (NENs). Early detection is crucial to improve prognosis. The value of the recommended screening biomarker, NT-proBNP, is uncertain. Biomarkers reflecting extracellular matrix (ECM) remodeling may capture early fibrogenesis. We aimed to evaluate circulating ECM biomarkers for the detection of CHD and to compare their performance with NT-proBNP. Design and methods: In this cross-sectional study, we prospectively included patients with disseminated small intestinal NENs (siNENs). We performed transthoracic echocardiography (TTE) for CHD diagnosis, and blood samples were analyzed for 10 ECM biomarkers. Biomarker levels were compared between patients with and without CHD, and diagnostic performance was assessed using the area under the receiver operating characteristic (AUROC) curve. Results: Among 98 patients, 16 (16%) had CHD. PRO-C3 levels were significantly elevated in patients with CHD compared with patients without CHD (median: 19.3 ng/mL (IQR: 15.6–24.0) vs 14.3 ng/mL (IQR: 12.4–17.5), P = 0.002). The AUROC curve of PRO-C3 for CHD detection was 0.77 (95% CI: 0.64–0.90). At a cutoff level of 15.4 ng/mL, the sensitivity was 85%, the specificity was 56%, the positive predictive value was 27%, and the negative predictive value was 95%. In the direct comparison between PRO-C3 and NT-proBNP, PRO-C3 did not outperform NT-proBNP (P = 0.09). Conclusion: PRO-C3, reflecting collagen type III formation, demonstrated good performance in CHD detection and may represent a complementary or potentially earlier marker than NT-proBNP. However, the performance of PRO-C3 was insufficient as a stand-alone tool, and further evaluation and exploration of new biomarkers in larger cohorts is required.
SN - 2634-4793
ER -