Construction of mitochondrial signature (MS) for the prognosis of ovarian cancer

TL;DR

This study identifies mitochondrial genes linked to ovarian cancer prognosis and introduces a new biomarker, OAT, for predicting patient survival and immune response.

Contribution

The novel contribution is the construction of a mitochondrial signature (MS) and the identification of OAT as a new prognostic biomarker for ovarian cancer.

Findings

21 mitochondria-related genes were identified to construct a prognostic model with strong performance in ovarian cancer.

OAT is a novel biomarker associated with poor survival and immune escape in ovarian cancer patients.

High OAT expression was confirmed in ovarian cancer cell lines compared to normal cells.

Abstract

Ovarian cancer (OV) continues to be the most lethal type of gynecological cancer with a poor prognosis. During tumorigenesis and cancer advancement, mitochondria are key players in energy metabolism. This study focuses on exploring the mitochondria-related genes for the prognosis of OV.

RNA expression profiles and single-cell data were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus databases for screening and validating mitochondria-related differentially expressed genes (DEGs). After univariate Cox analysis, prognostic genes were carried out for modeling mitochondria signature (MS) based on 101 combinations of 10 machine learning algorithms. Functional enrichment analysis was performed on this prognostic gene set. Immune infiltration analysis was performed between MS groups. Validation for the prognostic model gene OAT was performed to identify the prognostic significance, combined with in vitro experiments to explore its expressions in OV cells. qRT-PCR assay was performed to examine the expression of OAT in human ovarian cancer cell samples and normal ovarian epithelial cells.

A total of 21 prognostic mitochondria-related DEGs were identified for reliably constructing the model MS with excellent prognostic performance in OV. GO and KEGG analysis confirmed these genes were enriched in the generation of precursor metabolites and energy. It illustrated more lymphocyte infiltration in the high MS group than low MS group. OAT served as a novel biomarker for OV patients, showing poor survival in OV patients with high expression of OAT. qPCR assays confirmed its significantly high expression in human ovary cancer cell lines.

The MS offers tailored risk evaluations and immunotherapy treatments for each OV patient. MS model gene OAT has been recognized as a new oncogene for OV linked to immune escape.

The online version contains supplementary material available at 10.1007/s12672-025-02892-7.

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