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

Sho Sato; Michael Gillette; Pamela R. de Santiago; Eric Kuhn; Michael Burgess; Kristen Doucette; Yi Feng; Carlos Mendez-Dorantes; Paul J. Ippoliti; Sara Hobday; Marilyn A. Mitchell; Kai Doberstein; Stefan M. Gysler; Michelle S. Hirsch; Lauren Schwartz; Michael J. Birrer; Steven J. Skates; Kathleen H. Burns; Steven A. Carr; Ronny Drapkin

doi:10.1038/s41598-023-28840-5

Scientific Reports (Jan 2023)

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

Sho Sato,
Michael Gillette,
Pamela R. de Santiago,
Eric Kuhn,
Michael Burgess,
Kristen Doucette,
Yi Feng,
Carlos Mendez-Dorantes,
Paul J. Ippoliti,
Sara Hobday,
Marilyn A. Mitchell,
Kai Doberstein,
Stefan M. Gysler,
Michelle S. Hirsch,
Lauren Schwartz,
Michael J. Birrer,
Steven J. Skates,
Kathleen H. Burns,
Steven A. Carr,
Ronny Drapkin

Affiliations

Sho Sato: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Michael Gillette: The Broad Institute of MIT and Harvard
Pamela R. de Santiago: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Eric Kuhn: The Broad Institute of MIT and Harvard
Michael Burgess: The Broad Institute of MIT and Harvard
Kristen Doucette: The Broad Institute of MIT and Harvard
Yi Feng: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Carlos Mendez-Dorantes: Department of Oncologic Pathology, Dana-Farber Cancer Institute
Paul J. Ippoliti: The Broad Institute of MIT and Harvard
Sara Hobday: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Marilyn A. Mitchell: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Kai Doberstein: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Stefan M. Gysler: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine
Michelle S. Hirsch: Department of Pathology, Brigham and Women’s Hospital
Lauren Schwartz: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania
Michael J. Birrer: Department of Medicine, University of Alabama at Birmingham
Steven J. Skates: Harvard Medical School
Kathleen H. Burns: Harvard Medical School
Steven A. Carr: The Broad Institute of MIT and Harvard
Ronny Drapkin: Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine

DOI: https://doi.org/10.1038/s41598-023-28840-5
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 15

Abstract

Read online

Abstract 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.

Published in Scientific Reports

ISSN: 2045-2322 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://www.nature.com/srep/

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