Integrating Bioinformatics and Experimental Validation to Identify Mitochondrial Permeability Transition-Driven Necrosis-Related lncRNAs that can Serve as Prognostic Biomarkers and Therapeutic Targets in Endometrial Carcinoma

Ting Zhou ¹, Haojia Li ¹, Qi Zhang ¹

⁰Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

Reproductive Sciences (thousand Oaks, Calif.) +

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October 1, 2024

View abstract on PubMed

Summary

A new prognostic model using nine mitochondrial permeability transition (MPT)-driven necrosis related long non-coding RNAs (MRLs) can predict endometrial carcinoma (EC) patient outcomes and immunotherapy response. This model identifies high-risk patients with poorer survival and potential therapeutic targets.

Area Of Science

Oncology
Molecular Biology
Genomics

Background

Endometrial carcinoma (EC) presents significant challenges due to high mortality and relapse rates.
Mitochondrial permeability transition (MPT)-driven necrosis is an emerging programmed cell death pathway.
The role of MPT-driven necrosis related long non-coding RNAs (MRLs) in EC pathogenesis is largely unknown.

Purpose Of The Study

To develop and validate a novel prognostic model for endometrial carcinoma based on MRLs.
To explore the molecular functions and pathways associated with MRLs in EC.
To assess the model's ability to predict patient outcomes and immunotherapy response.

Main Methods

Construction of a risk prognostic model using multi-Cox and LASSO regression based on MRLs.
Evaluation of model performance using ROC curve analysis, nomogram, and concordance index (C-index).
Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Dysfunction and Exclusion (TIDE) analysis.

Main Results

A nine-MRLs-based risk model effectively stratified patients into high- and low-risk groups with distinct overall survival (OS) outcomes.
The high-risk group showed enrichment in Hedgehog and cell cycle pathways, indicating immune evasion and reduced immunotherapy efficacy.
OGFRP1 was identified as a carcinogenic MRL affecting mitochondrial membrane permeability in EC.

Conclusions

The developed nine-MRL prognostic model accurately predicts clinical outcomes and therapeutic responses in EC patients.
This model offers insights into EC molecular mechanisms, including immune evasion and potential therapeutic targets.
The findings highlight the prognostic and potential therapeutic significance of MRLs in endometrial carcinoma management.

Keywords:

Biomarkers Endometrial carcinoma LncRNAs Mitochondrial permeability transition Prognostic signature

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