The Clinical Significance of CRNDE Gene Methylation, Polymorphisms, and CRNDEP Micropeptide Expression in Ovarian Tumors

Sep 21, 2026

Uploaded by Liam

CRNDE is characterized as an oncogene long non-coding RNA, but it also encodes a micropeptide, CRNDEP. This study evaluates genetic alterations in the CRNDEP-coding region, CRNDE methylation profiles, and CRNDEP expression in clinical ovarian tumor samples spanning diverse aggressiveness. CRNDEP is elevated in highly aggressive tumors and serves as a negative independent prognostic and predictive factor in high-grade ovarian cancer. No CRNDEP-disrupting mutations are detected, while rs115515594 increases recurrence risk specifically in borderline ovarian tumors. Hypomethylation of CRNDE, including the promoter/first exon, associates with greater aggressiveness, chemotherapy resistance in high-grade disease under TP53 accumulation.

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CategoryResearch & Report

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Abstract

Introduction

Article The Clinical Significance of CRNDE Gene Methylation, Polymorphisms, and CRNDEP Micropeptide Expression in Ovarian Tumors Laura Aleksandra Szafron 1, *, Roksana Iwanicka-Nowicka 2,3, Agnieszka Podgorska 4, Arkadiusz M. Bonna 5, Piotr Sobiczewski 6, Jolanta Kupryjanczyk 7 and Lukasz Michal Szafron 1, * Citation: Szafron, L.A.; Iwanicka-Nowicka, R.; Podgorska, A.; Bonna, A.M.; Sobiczewski, P.; Kupryjanczyk, J.; Szafron, L.M. The Clinical Significance of CRNDE Gene Methylation, Polymorphisms, and CRNDEP Micropeptide Expression in Ovarian Tumors. Int. J. Mol. Sci. 2024, 25, 7531. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25147531 Academic Editors: Alessandro Mangogna, Laura Mariuzzi and Maria Orsaria Received: 28 April 2024 Revised: 30 June 2024 Accepted: 5 July 2024 Published: 9 July 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland 2 Laboratory of Systems Biology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland 3 Laboratory for Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland 4 Cancer Molecular and Genetic Diagnostics Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland 5 Triple Helical Peptides Ltd., Cambridge CB22 5DU, UK; [abonna@peptidebiochem.eu](abonna@peptidebiochem.eu) [6](6 Department of Gynecological Oncology)[ Department of Gynecological Oncology](6 Department of Gynecological Oncology), [Maria Sklodowska-Curie National Research Institute of Oncology](Maria Sklodowska-Curie National Research Institute of Oncology), 02-781 Warsaw, Poland 7 Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; [jolanta.kupryjanczyk@nio.gov.pl](jolanta.kupryjanczyk@nio.gov.pl) * Correspondence: [laura.szafron@gmail.com](laura.szafron@gmail.com) (L.A.S.); [lukszafron@gmail.com](lukszafron@gmail.com) (L.M.S.) Abstract: CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEPdisrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene’s promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of t

FAQs

What was the study’s main objective regarding CRNDE and CRNDEP in ovarian tumors?

To assess genetic alterations in the CRNDEP-coding region, perform CRNDE methylation profiling, and analyze CRNDEP expression in patient materials from ovarian tumors with different aggressiveness levels.

How does CRNDEP expression relate to ovarian tumor aggressiveness and prognosis?

CRNDEP levels are significantly higher in highly aggressive tumors than in benign neoplasms, and high CRNDEP acts as a negative independent prognostic and predictive factor in high-grade ovarian cancer patients.

Which genetic and epigenetic findings were linked to recurrence risk and tumor aggressiveness?

A single nucleotide polymorphism rs115515594 increases recurrence risk in borderline ovarian tumors, and CRNDE hypomethylation correlates with increased tumor aggressiveness; promoter/first exon hypomethylation is associated with chemotherapy resistance in high-grade ovarian cancer specimens with TP53 accumulation.

Sep 21, 2026

Uploaded by Liam