Evidence map›Paper›PMID 39838687›Full record

ArticleCurrent medicinal chemistry2025

The Expression of the LDLR, LDLRAP1, and PCSK9 Genes has Prognostic Significance in Triple-negative Breast Cancer.

Ivan Denisovich Antipenko, Darya Mikhailovna Olkhovik, Olga Nikolaevna Solopova, Gulfia Amirovna Khayretdinova, Olga Sergeevna Kalacheva, Julia Alekseevna Makarova, Maxim Yurievich Shkurnikov

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Article in Current medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2 citing papers in PubMed.

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5 · Who and what money

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7 authors.

Ivan Denisovich AntipenkoLaboratory for Research on Molecular Mechanisms of Longevity, Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
Darya Mikhailovna OlkhovikLaboratory of Microphysiological Systems, Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
Olga Nikolaevna SolopovaResearch Institute of Experimental Diagnostics and Tumor Therapy, Blokhin National Medical Research Center of Oncology, Moscow, Russia.
Gulfia Amirovna KhayretdinovaClinical Department, Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia.
Olga Sergeevna KalachevaCenter of Extracorporeal Therapies, MEDSI Clinic, Moscow, Russia.
Julia Alekseevna MakarovaJoint Department with RAS Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
Maxim Yurievich ShkurnikovLaboratory for Research on Molecular Mechanisms of Longevity, Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe purpose of this study was to investigate the prognostic significance of cholesterol uptake genes in predicting the survival of breast cancer patients.

backgroundCholesterol plays a crucial role in the homeostasis of tumor cells. It is known that cholesterol levels can influence important parameters of the disease, such as sensitivity to therapy, progression, and metastasis of cancer. Previous studies suggest that breast cancer subtypes exhibit differences in metabolism.

objectiveThe objectives of this study were to determine whether cholesterol uptake genes have prognostic significance for overall survival in breast cancer patients, evaluate if this prognostic significance varies between breast cancer subtypes, and identify differences in the expression of cholesterol uptake genes among these subtypes.

methodsData from mRNA sequencing of tumors from the Cancer Genome Atlas (TCGA) portal were analyzed. Tumors were classified into molecular subtypes, and the prognostic significance of cholesterol uptake gene expression levels was evaluated for each subtype. DESeq2 and Fisher's test were used to assess differences in gene expression.

resultsHigh expression levels of genes involved in de novo cholesterol synthesis were associated with poor prognosis for the Basal-like and Luminal A breast cancer subtypes. The prognostic significance of low-density lipoprotein receptor (LDLR), LDLR adapter protein 1 (LDLRAP1), and proprotein convertase subtilisin/kexin type 9 (PCSK9), which are responsible for exogenous cholesterol uptake, varied across subtypes. Specifically, low expression of LDLR was associated with a favorable prognosis for the luminal A (OR = 2.17; FDR = 0.0048) and luminal B (OR = 2.21; FDR = 0.015) subtypes but indicated poor prognosis in the basal-like subtype (OR = 0.48; FDR = 0.05). No genes were significant for prognosis prediction in the HER2-positive subtype. The HER2+ subtype exhibited higher expression of cholesterol uptake genes compared to the basal-like subtype based on the analysis of tumor mRNA sequencing (OR = 6.45, p-value = 3.07E-05). This finding was also confirmed through the study of publicly available single-cell sequencing data (OR = 40.3, p-value = 2.19e-07), which may contribute to the differences in their prognostic significance.

conclusionThe prognostic significance of cholesterol uptake gene expression varies among breast cancer subtypes. Precise fitting of biomarkers into breast cancer subtypes may aid in more accurate patient stratification and improve treatment approaches.

Indexed as

Adaptor Proteins, Signal TransducingProprotein Convertase 9Receptors, LDLTriple Negative Breast NeoplasmsCholesterolFemaleGene Expression Regulation, NeoplasticHumansPrognosisAdaptor Proteins, Signal TransducingCholesterolLDLRAP1 protein, humanLDLR protein, humanPCSK9 protein, humanProprotein Convertase 9Receptors, LDLbasal-like.Breast cancercholesterolHER2+LDLRPCSK9triple-negative

Identifiers

PMID39838687

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