Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation

Jesus Gonzalez Bosquet; Vincent Wagner; Andrew Polio; Katharine E Linder; David P Bender; Michael J Goodheart; Brandon M Schickling

doi:10.3390/ijms26031347

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Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation

Journal article

Open access

Peer reviewed

Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation

Jesus Gonzalez Bosquet, Vincent Wagner, Andrew Polio, Katharine E Linder, David P Bender, Michael J Goodheart and Brandon M Schickling

International journal of molecular sciences, Vol.26(3), 1347

02/05/2025

DOI: 10.3390/ijms26031347

PMCID: PMC11818617

PMID: 39941116

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Abstract

Women diagnosed with advanced-stage ovarian cancer have a much worse survival rate than women diagnosed with early-stage ovarian cancer, but the early detection of this disease remains a clinical challenge. Some recent reports indicate that genetic variations could be useful for the early detection of several malignancies. In this pilot observational retrospective study, we aimed to assess whether mitochondrial DNA (mtDNA) variations could discriminate the most frequent type of ovarian cancer, high-grade serous carcinoma (HGSC), from normal tissue. We identified mtDNA variations from 20 whole-exome sequenced (WES) HGSC samples and 14 controls (normal tubes) using the best practices of genome sequencing. We built prediction models of cancer with these variants, with good performance measured by the area under the curve (AUC) of 0.88 (CI: 0.74-1.00). The variants included in the best model were correlated with gene expression to assess the potentially affected processes. These analyses were validated with the Cancer Genome Atlas (TCGA) dataset, (including over 420 samples), with a fair performance in AUC terms (0.63-0.71). In summary, we identified a set of mtDNA variations that can discriminate HGSC with good performance. Specifically, variations in the gene increased the risk for HGSC by over 30%, and expression was significantly decreased in HGSC patients. Robust models of ovarian cancer detection with mtDNA variations could be applied to liquid biopsy technology, like those which have been applied to other cancers, with a special focus on the early detection of this lethal disease.

Aged

Cystadenocarcinoma, Serous - genetics

Cystadenocarcinoma, Serous - pathology

DNA, Mitochondrial - genetics

Exome Sequencing - methods

Female

Genes, Mitochondrial - genetics

Genetic Variation

Humans

Middle Aged

Neoplasm Grading

Ovarian Neoplasms - genetics

Ovarian Neoplasms - pathology

Retrospective Studies

Details

Title: Subtitle: Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation
Creators: Jesus Gonzalez Bosquet - Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
Vincent Wagner - University of Iowa
Andrew Polio - University of Iowa
Katharine E Linder - University of Iowa
David P Bender - University of Iowa
Michael J Goodheart - University of Iowa
Brandon M Schickling - University of Iowa
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.26(3), 1347
DOI: 10.3390/ijms26031347
PMID: 39941116
PMCID: PMC11818617
NLM abbreviation: Int J Mol Sci
ISSN: 1422-0067
eISSN: 1422-0067
Publisher: MDPI
Grant note: 2016 / University of Iowa Department of Obstetrics and Gynecology AAOGF 2018 / American Association of Obstetricians and Gynecologists Foundation (AAOGF) Bridge Funding Award 5R01CA99908-18 / NIH HHS
Language: English
Date published: 02/05/2025
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984787234802771

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