Evidence map›Paper›PMID 39885513›Full record

ArticleJournal of translational medicine2025

Identification and validation of a prognostic signature of drug resistance and mitochondrial energy metabolism-related differentially expressed genes for breast cancer.

Tiankai Xu, Chu Chu, Shuyu Xue, Tongchao Jiang, Ying Wang, Wen Xia, Huanxin Lin

Abstract readValidation Study
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Tiankai Xu *Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Chu Chu *Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Shuyu Xue *Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Tongchao JiangDepartment of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Ying WangDepartment of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Wen XiaDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Huanxin LinDepartment of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. linhx@sysucc.org.cn.ORCID 0000-0002-0621-4486

Funding

Basic and Applied Basic Research Foundation of Guangdong Province Grant No. 202201010918National Natural Science Foundation of China Grant No.82102838National Natural Science Foundation of China Grant No. 82103437Natural Science Foundation of Guangdong Province No.2023A1515010685
6 · The paper itself

Abstract

backgroundDrug resistance constitutes one of the principal causes of poor prognosis in breast cancer patients. Although cancer cells can maintain viability independently of mitochondrial energy metabolism, they remain reliant on mitochondrial functions for the synthesis of new DNA strands. This dependency underscores a potential link between mitochondrial energy metabolism and drug resistance. Hence, drug resistance and mitochondrial energy metabolism-related differentially expressed genes (DMRDEGs) may emerge as candidates for novel cancer biomarkers. This study endeavors to assess the viability of DMRDEGs as biomarkers or therapeutic targets for breast cancer.

methodsWe utilized the DRESIS database and MSigDB to identify genes related to drug resistance. Additionally, we sourced genes associated with mitochondrial energy metabolism from GeneCards and extant literature. By merging these genes with differentially expressed genes observed in normal and tumor tissues from the TCGA-BRCA and GEO databases, we successfully identified the DMRDEGs. Employing unsupervised consensus clustering, we divided breast cancer patients into two distinct groups based on the DMRDEGs. Consequently, we identified four hub genes to formulate a prognostic model, applying Cox regression, LASSO regression, and Random Forest methods. Furthermore, we examined immune infiltration and tumor mutation burden of the genes within our model and scrutinized divergences in the immune microenvironment between high- and low-risk groups. Small hairpin RNA and lentiviral plasmids were designed for stable transfection of breast cancer cell lines MDA-MB-231 and HCC1806. By conducting clone formation, scratch test, transwell assays, cell viability assay and measurement of oxygen consumption we initiated a preliminary investigation into mechanistic roles of AIFM1.

resultsWe utilized DMRDEGs to develop a prognostic model that includes four mRNAs for breast cancer. This model combined with various clinical features and critical breast cancer facets, demonstrated remarkable efficacy in predicting patient outcomes. AIFM1 appeared to enhance the proliferation, migration, and invasiveness of breast cancer cell lines MDA-MB-231 and HCC1806. Moreover, by reducing oxygen consumption, it aids in the cancer cells' acquisition of drug resistance.

conclusionsDMRDEGs hold promise as diagnostic markers and therapeutic targets for breast cancer. Among the associated mutated genes, ATP7B, FUS, AIFM1, and PPARG could serve as early diagnostic indicators, and notably, AIFM1 may present itself as a promising therapeutic target.

Indexed as

Breast NeoplasmsDrug Resistance, NeoplasmEnergy MetabolismGene Expression ProfilingGene Expression Regulation, NeoplasticMitochondriaCell Line, TumorCluster AnalysisFemaleHumansPrognosisReproducibility of ResultsBreast cancerDrug resistanceMitochondrial energy metabolismPrognostic model

Identifiers

PMID39885513
PMCPMC11780791

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.