Evidence map›Paper›PMID 40576911›Full record

ArticleGeroScience2026

PCSK9 expression and cancer survival: a prognostic biomarker at the intersection of oncology and geroscience.

Zoltan Ungvari, Otília Menyhart, Andrea Lehoczki, Monika Fekete, Giampaolo Bianchini, Balázs Győrffy

Abstract read
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
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

6 authors.

Zoltan UngvariVascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Otília MenyhartCancer Biomarker Research Group, Institute of Molecular Life Sciences, Hungarian Research Network, Magyar Tudósok Körútja 2, 1117, Budapest, Hungary.
Andrea LehoczkiDoctoral College, Health Sciences Division, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.ORCID 0000-0002-4285-7518
Monika FeketeInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Giampaolo BianchiniDepartment of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
Balázs GyőrffyCancer Biomarker Research Group, Institute of Molecular Life Sciences, Hungarian Research Network, Magyar Tudósok Körútja 2, 1117, Budapest, Hungary.

Funding

Cerebral microhemorrhages and gait dysfunction in agingR01AG055395 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2017 to 2025
$2.3M
Age-related vascular cognitive impairment: role of endothelial senescenceR01AG068295 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA, UNGVARI, ZOLTAN ISTVAN · 2020 to 2024
$1.8M
The role of IGF-1 signaling in vascular smooth muscle cells in age-related vascular cognitive impairment and dementiaR01AG070915 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CONLEY, SHANNON M · 2021 to 2025
$1.8M
Radiation-induced astrocyte dysfunction and cognitive declineR01NS100782 · NINDS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI UNGVARI, ZOLTAN ISTVAN · 2018 to 2022
$1.7M
Chemotherapy-induced vascular cognitive impairment: role of endothelial senescenceR01CA255840 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2021 to 2025
$1.6M
Cerebromicrovascular rejuvenation by heterochronic blood exchangeRF1AG072295 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA, UNGVARI, ZOLTAN ISTVAN · 2021 to 2021
$1.4M
NCI NIH HHS R01 CA255840NIA NIH HHS R01 AG055395NIA NIH HHS R01 AG068295NIA NIH HHS R01 AG070915NIA NIH HHS RF1 AG072295NINDS NIH HHS R01 NS100782
6 · The paper itself

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in cholesterol metabolism; however, emerging evidence suggests it plays a broader role in the regulation of cellular aging mechanisms and the pathogenesis of age-related diseases. Given that cancer is an age-related disease, PCSK9 has garnered attention for its potential impact on tumor progression and patient survival. In this study, we conducted a comprehensive analysis of PCSK9 expression across multiple tumor types, assessing its prognostic significance using RNA sequencing data from The Cancer Genome Atlas (TCGA) and gene expression microarray data from the Gene Expression Omnibus (GEO). Cox proportional hazards regression models and Kaplan-Meier survival analyses were employed to evaluate overall survival (OS) associations. Our findings reveal that elevated PCSK9 expression is associated with improved OS in breast and ovarian cancers, particularly in Luminal B breast cancer subtypes. Conversely, high PCSK9 expression correlates with worse OS in bladder cancer, renal clear cell carcinoma, melanoma, and pancreatic cancer. Notably, while PCSK9 expression is significantly upregulated in melanoma and bladder tumors, it is downregulated in renal clear cell carcinoma, yet relatively higher expression among renal tumors still predicts poorer survival. No significant associations between PCSK9 expression and OS were observed in colon, liver, gastric, lung, prostate, head and neck cancers, or low-grade gliomas in the available datasets.In conclusion, our study identifies PCSK9 as a prognostic biomarker with distinct, tumor-specific survival implications. Its dual role-associating with improved survival in some cancers while correlating with worse outcomes in others-suggests that PCSK9 may influence cancer progression through context-dependent mechanisms. Future research should focus on elucidating the mechanistic underpinnings of these associations and exploring the diagnostic and therapeutic potential of targeting PCSK9 in oncology.

Indexed as

Biomarkers, TumorNeoplasmsProprotein Convertase 9FemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMalePrognosisBiomarkers, TumorPCSK9 protein, humanProprotein Convertase 9AgingBiomarkersBreast cancerCancer survivalCholesterol metabolismImmune modulationImmunotherapyLifestyle factorsLipid metabolismMetastasisOncologyPCSK9PrognosisTumor microenvironmentTumor progressionVascular aging

Identifiers

PMID40576911
PMCPMC12972280

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.