Evidence map›Paper›PMID 40394523›Full record

ArticleBMC cancer2025

Proteolytic degradation of Beta-Ig H3 (βigH3/TGFBI) can be quantified non-invasively in serum and predicts prognosis in patients with advanced pancreatic ductal adenocarcinoma.

Rasmus S Pedersen, Annika Hettich, Jeppe Thorlacius-Ussing, Lasse L Langholm, Marina Crespo-Bravo, Inna M Chen, Carsten P Hansen, Julia S Johansen, Hadi M H Diab, Lars N Jorgensen and 2 more

Abstract read
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Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Rasmus S PedersenNordic Bioscience A/S, 2730, Herlev, Denmark. rap@nordicbio.com.
Annika HettichNordic Bioscience A/S, 2730, Herlev, Denmark.
Jeppe Thorlacius-UssingNordic Bioscience A/S, 2730, Herlev, Denmark.
Lasse L LangholmNordic Bioscience A/S, 2730, Herlev, Denmark.
Marina Crespo-BravoNordic Bioscience A/S, 2730, Herlev, Denmark.
Inna M ChenDepartment of Oncology, Copenhagen University Hospital - Herlev and Gentofte, 2730, Herlev, Denmark.
Carsten P HansenDepartment of Surgery, Copenhagen University Hospital - Rigshospitalet, 2100, Copenhagen, Denmark.
Julia S JohansenDepartment of Oncology, Copenhagen University Hospital - Herlev and Gentofte, 2730, Herlev, Denmark.
Hadi M H DiabDigestive Disease Center, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400, Copenhagen, Denmark.
Lars N JorgensenDigestive Disease Center, Copenhagen University Hospital - Bispebjerg and Frederiksberg, 2400, Copenhagen, Denmark.
Morten KarsdalNordic Bioscience A/S, 2730, Herlev, Denmark.
Nicholas WillumsenNordic Bioscience A/S, 2730, Herlev, Denmark.

Funding

Danish Cancer Society R218-A13160
6 · The paper itself

Abstract

The extracellular matrix (ECM) protein Beta-Ig H3 (βigH3, also known as transforming growth factor β induced protein (TGFBI)) is related to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Proteolytic cleavage of βigH3 has been shown to result in release of the N-terminal fragment covering amino acid 1 to 137, but whether the degradation of βigH3 is associated to prognosis has yet to be determined. In this study we developed an ELISA targeting a collagenase generated fragment of βigH3 (cβigH3) in human serum to use the fragment as a biomarker reflecting degradation of βigH3. We demonstrated that the assay was specific to the cleaved fragment (cβigH3) and confirmed the generation of cβigH3 from degradation of fibroblast generated matrices. Moreover, higher levels of cβigH3 were released upon degradation of matrices produced by TGF-β stimulated pancreatic fibroblast compared to matrices produced by pancreatic fibroblast without TGF-β stimulation, indicating an association of the biomarker with degradation of fibrotic matrix. To evaluate the clinical relevance, we first measured cβigH3 in a cohort of 220 patients with different types of cancer with detectable levels for all 11 cancer types. We then measured the cβigH3 biomarker in pre-treatment serum from a cohort of 469 patients with locally advanced or metastatic PDAC and found that high levels of cβigH3 were associated with longer overall survival independently of age, disease stage, performance status, carbohydrate antigen 19-9 (CA19-9), and the tumor fibrosis biomarker PRO-C3 as compared to patients with high levels of cβigH3 (HR 0.78, 95% CI: 0.0.61-0.98, p = 0.04). In conclusion, cβigH3 reflects proteolytic degradation of βigH3 and shows potential as an independent prognostic biomarker for patients with advanced PDAC.

Indexed as

Biomarkers, TumorCarcinoma, Pancreatic DuctalExtracellular Matrix ProteinsPancreatic NeoplasmsTransforming Growth Factor betaAgedbetaIG-H3 ProteinEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMiddle AgedPrognosisProteolysisbetaIG-H3 ProteinBiomarkers, TumorExtracellular Matrix ProteinsTransforming Growth Factor beta

Identifiers

PMID40394523
PMCPMC12093888

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.