Model-based inference of metastatic seeding rates in de novo metastatic breast cancer reveals the impact of secondary seeding and molecular subtype.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 06 2022
Historique:
received: 09 09 2021
accepted: 08 03 2022
entrez: 8 6 2022
pubmed: 9 6 2022
medline: 11 6 2022
Statut: epublish

Résumé

We present a stochastic network model of metastasis spread for de novo metastatic breast cancer, composed of tumor to metastasis (primary seeding) and metastasis to metastasis spread (secondary seeding), parameterized using the SEER (Surveillance, Epidemiology, and End Results) database. The model provides a quantification of tumor cell dissemination rates between the tumor and metastasis sites. These rates were used to estimate the probability of developing a metastasis for untreated patients. The model was validated using tenfold cross-validation. We also investigated the effect of HER2 (Human Epidermal Growth Factor Receptor 2) status, estrogen receptor (ER) status and progesterone receptor (PR) status on the probability of metastatic spread. We found that dissemination rate through secondary seeding is up to 300 times higher than through primary seeding. Hormone receptor positivity promotes seeding to the bone and reduces seeding to the lungs and primary seeding to the liver, while HER2 expression increases dissemination to the bone, lungs and primary seeding to the liver. Secondary seeding from the lungs to the liver seems to be hormone receptor-independent, while that from the lungs to the brain appears HER2-independent.

Identifiants

pubmed: 35676303
doi: 10.1038/s41598-022-12500-1
pii: 10.1038/s41598-022-12500-1
pmc: PMC9177582
doi:

Substances chimiques

Biomarkers, Tumor 0
Hormones 0
Receptors, Estrogen 0
Receptors, Progesterone 0
Receptor, ErbB-2 EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9455

Informations de copyright

© 2022. The Author(s).

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Auteurs

Noemi Vitos (N)

Bla Kustens Halsocentral, 57251, Oskarshamn, Sweden.

Philip Gerlee (P)

Mathematical Sciences, Chalmers University of Technology, 41296, Gothenburg, Sweden. gerlee@chalmers.se.
Mathematical Sciences, University of Gothenburg, 41296, Gothenburg, Sweden. gerlee@chalmers.se.

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