Evidence map›Paper›PMID 41990272›Full record

ArticleCancer research communications2026

Multiplexed P21/MCM-2 Detection Predicts Relapse and May Identify Tyrosine Kinase Inhibitor-Resistant Patients in Clear Cell Renal Cell Carcinoma.

Hazem Abdullah, In Hwa Um, Grant D Stewart, Chang Wook Jeong, Cheol Kwak, Kyung Chul Moon, Alexander Laird, Elena Frangou, Tim Eisen, Angela Meade and 1 more

Abstract read
In one paragraph

Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Hazem AbdullahSchool of Medicine, University of St Andrews, St Andrews, United Kingdom.ORCID 0009-0003-3476-6258
In Hwa UmSchool of Medicine, University of St Andrews, St Andrews, United Kingdom.ORCID 0000-0001-9999-4292
Grant D StewartDepartment of Surgery, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-3188-9140
Chang Wook JeongDepartment of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-2200-5019
Cheol KwakDepartment of Urology, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-1987-2111
Kyung Chul MoonDepartment of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-1969-8360
Alexander LairdDepartment of Urology, Western General Hospital, Edinburgh, United Kingdom.ORCID 0000-0002-7296-025X
Elena FrangouMedical Research Council Clinical Trials Unit at University College London (UCL) , Institute of Clinical Trials and Methodology, London, United Kingdom.ORCID 0000-0002-5978-292X
Tim EisenDepartment of Oncology, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-9663-4873
Angela MeadeMedical Research Council Clinical Trials Unit at University College London (UCL) , Institute of Clinical Trials and Methodology, London, United Kingdom.ORCID 0000-0001-6424-0554
David J HarrisonSchool of Medicine, University of St Andrews, St Andrews, United Kingdom.ORCID 0000-0001-9041-9988

Funding

European Commission (EC) 101017453University of St Andrews (The University of St Andrews) Sanctuary scholarship
6 · The paper itself

Abstract

Current clinical tools for predicting relapse and guiding adjuvant therapy in clear cell renal cell carcinoma (ccRCC) lack precision, especially in intermediate-risk disease. This study evaluated whether a nonproliferative tumor cell phenotype, P21 (CDKN1A inhibitor)-positive and MCM2 (DNA replication protein)-negative (P21+/MCM2-), could serve as a robust biomarker to improve prognostic stratification and guide postnephrectomy treatment decisions. We used multiplex immunofluorescence and Artificial Intelligence-based image analysis on nephrectomy specimens from three independent ccRCC cohorts: UK arm of the SORCE trial (n = 382), Korean (n = 71), and Scottish (n = 88). An optimal 2% cutoff for P21+/MCM2- cells was determined using X-tile software. Additional analyses assessed endoglin/CD105 coexpression, paired primary-metastatic samples (n = 41), and associations with adjuvant sorafenib therapy. In two intermediate-risk ccRCC cohorts (SORCE, n = 63; Korean, n = 71), patients with >2% P21+/MCM2- cells had significantly longer time to relapse [HR = 0.17; 95% confidence interval (CI), 0.06-0.54; HR = 0.27; 95% CI, 0.10-0.72]. Prognostic value was confirmed in high-risk (SORCE, HR = 0.43; 95% CI, 0.19-0.99) and all-risk (Scottish, HR = 0.37; 95% CI, 0.14-0.98) cohorts. Notably, patients with high P21+/MCM2- levels on placebo fared better than those receiving adjuvant TKI therapy (HR = 0.29; 95% CI, 0.16-0.50). In 41 paired samples, 85% showed higher P21+/MCM2- abundance in metastases than in primary tumors. As a conclusion, P21+/MCM2- cell count is a robust biomarker that refines relapse risk stratification in ccRCC and identifies patients who may not benefit from adjuvant tyrosine kinase inhibitor (TKI) therapy. High levels of these nonproliferative, senescent-like cells suggest tumor dormancy and a more favorable outcome without treatment. SIGNIFICANCE: After surgery for clear cell renal cell carcinoma, relapse risk and benefit from adjuvant therapy remain uncertain. We identify a distinct P21+/MCM2- tumor phenotype, nonproliferative and senescent-like, linked to favorable outcomes. Across three cohorts, >2% of these cells reduced relapse risk, but benefit was lost with adjuvant TKIs.

Indexed as

Carcinoma, Renal CellCyclin-Dependent Kinase Inhibitor p21Drug Resistance, NeoplasmKidney NeoplasmsMinichromosome Maintenance Complex Component 2Neoplasm Recurrence, LocalProtein Kinase InhibitorsAgedBiomarkers, TumorFemaleHumansMaleMiddle AgedNephrectomyPrognosisBiomarkers, TumorCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21MCM2 protein, humanMinichromosome Maintenance Complex Component 2Protein Kinase Inhibitors

Identifiers

PMID41990272
PMCPMC13150819

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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.