LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma.


Journal

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

Informations de publication

Date de publication:
27 01 2023
Historique:
received: 16 08 2022
accepted: 25 01 2023
pubmed: 28 1 2023
medline: 1 2 2023
entrez: 27 1 2023
Statut: epublish

Résumé

Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.

Identifiants

pubmed: 36707610
doi: 10.1038/s41598-023-28840-5
pii: 10.1038/s41598-023-28840-5
pmc: PMC9883229
doi:

Substances chimiques

Biomarkers 0
Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1537

Subventions

Organisme : NCI NIH HHS
ID : U24 CA270823
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Sho Sato (S)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Michael Gillette (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Pamela R de Santiago (PR)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Eric Kuhn (E)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Michael Burgess (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Kristen Doucette (K)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Yi Feng (Y)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Carlos Mendez-Dorantes (C)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Paul J Ippoliti (PJ)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Sara Hobday (S)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Marilyn A Mitchell (MA)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Kai Doberstein (K)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Stefan M Gysler (SM)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Michelle S Hirsch (MS)

Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Lauren Schwartz (L)

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA.

Michael J Birrer (MJ)

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.

Steven J Skates (SJ)

Harvard Medical School, Boston, MA, 02115, USA.
Biostatistics and Computational Biology, Massachusetts General Hospital, Boston, MA, USA.

Kathleen H Burns (KH)

Harvard Medical School, Boston, MA, 02115, USA.
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Steven A Carr (SA)

The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Harvard Medical School, Boston, MA, 02115, USA.

Ronny Drapkin (R)

Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA. rdrapkin@pennmedicine.upenn.edu.
Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA. rdrapkin@pennmedicine.upenn.edu.

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