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

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

Sci Rep. 2023 Jan 27;13(1):1537. doi: 10.1038/s41598-023-28840-5.

Authors

Sho Sato^#¹, Michael Gillette^#^{2

3

4}, Pamela R de Santiago¹, Eric Kuhn², Michael Burgess², Kristen Doucette², Yi Feng¹, Carlos Mendez-Dorantes⁵, Paul J Ippoliti², Sara Hobday¹, Marilyn A Mitchell¹, Kai Doberstein¹, Stefan M Gysler¹, Michelle S Hirsch^{6

4}, Lauren Schwartz⁷, Michael J Birrer⁸, Steven J Skates^{4

9}, Kathleen H Burns^{4

5}, Steven A Carr^{2

4}, Ronny Drapkin^{10

11}

Affiliations

¹ Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
² The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
³ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁴ Harvard Medical School, Boston, MA, 02115, USA.
⁵ Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
⁷ Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁸ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
⁹ Biostatistics and Computational Biology, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA. rdrapkin@pennmedicine.upenn.edu.
¹¹ Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA. rdrapkin@pennmedicine.upenn.edu.

^# Contributed equally.

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.

Publication types

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

MeSH terms

Biomarkers / metabolism
Fallopian Tubes / metabolism
Female
Humans
Long Interspersed Nucleotide Elements
Ovarian Neoplasms* / pathology
Proteins / metabolism

Substances

Biomarkers
Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding