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Role of PCSK9 in breast cancer: a systematic review of its mechanistic pathways and clinical relevance
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DOI：10.3389/fphar.2026.1849027.png)
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Abstract
En 中文
IntroductionBreast cancer is a heterogeneous disease in which accurate classification based on biomarker expression is essential for effective therapeutic decision-making. Consequently; the identification of novel biomarkers remains a research priority. Proprotein convertase subtilisin/kexin type 9 (PCSK9); a key regulator of low-density lipoprotein (LDL) metabolism via its interaction with the LDL receptor (LDLR); has been extensively studied in cardiovascular disease. More recently; emerging evidence indicates that PCSK9 is highly expressed in several malignancies and may contribute to cancer progression; including in breast cancer.MethodsA systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. PubMed (NCBI); Scopus; and Google Scholar were searched for studies published between 9 and 16 September 2025. Eligible studies included experimental (in vitro; in vivo; and in silico) and clinical investigations evaluating the role of PCSK9 in breast cancer. Given the heterogeneity in study designs and outcomes; findings were synthesized narratively.ResultsNineteen studies met the inclusion criteria. Preclinical evidence consistently demonstrates that PCSK9 promotes tumorigenesis by enhancing cell proliferation; migration; invasion; and metastasis; supporting its potential as a biomarker and therapeutic target. However; clinical findings remain inconsistent; with conflicting evidence regarding the association between PCSK9 expression and patient prognosis.ConclusionIn conclusion; while preclinical studies indicate a pro-tumorigenic role for PCSK9; its clinical significance in breast cancer appears to be context-dependent. The effects of PCSK9 vary according to molecular subtype and are influenced by the tumor microenvironment. Further well-designed studies are needed to clarify its prognostic value and potential as a target for personalized therapy.
Keywords:
breast cancer
cancer progression
pcsk9
LDLR
clinical relevance
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