Evidence map›Paper›PMID 42680704›Full record

ArticleCancer reports (Hoboken, N.J.)2026

Age-Associated Four-Gene Prognostic Signature in Breast Cancer.

Shiro Uchida

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Article in Cancer reports (Hoboken, N.J.), 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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4 · The record

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5 · Who and what money

Authors and funding

1 author.

Shiro UchidaDivision of Diagnostic Pathology, Kikuna Memorial Hospital, Yokohama, Japan.ORCID 0000-0002-7086-896X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundYoung-onset breast cancer is associated with inferior disease-free survival (DFS), but the contribution of additional molecular heterogeneity remains unclear.

aimsTo identify an exploratory age-associated gene expression signature linked to recurrence-related outcomes and evaluate its prognostic association. METHODS AND

resultsWe analyzed clinicopathological and RNA-sequencing data from 821 patients with Stages I-III invasive ductal or lobular carcinoma in The Cancer Genome Atlas, including 142 patients aged ≤ 45 years. Genes associated with both age and DFS were screened, followed by LASSO-Cox and stepwise multivariable Cox regression. A four-gene signature (Sig4: C4orf14 [NOA1], LINC01124, ZNF704, and AGFG2) was identified. Young patients had significantly worse DFS than older patients, whereas overall and disease-specific survival did not differ significantly. After adjustment for clinicopathological factors, young age remained associated with worse DFS. Following inclusion of the continuous Sig4 score, the age association was attenuated and no longer statistically significant, while Sig4 remained independently associated with worse DFS. Sig4-high tumors were enriched for proliferation, cell-cycle, DNA-repair, metabolic, and stress-response pathways. In METABRIC, the fixed TCGA-derived Sig4 score was associated with worse relapse-free survival in the overall cohort but not in patients aged ≤ 45 years.

conclusionSig4 is an exploratory age-associated four-gene signature with potential general prognostic relevance in breast cancer. Its utility for risk stratification specifically in young-onset breast cancer was not externally validated and requires confirmation in independent prospective cohorts enriched for young patients.

Indexed as

Biomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularNeoplasm Recurrence, LocalTranscriptomeAdultAge FactorsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm StagingPrognosisBiomarkers, Tumorbreast cancerdisease‐free survivalthe cancer genome atlasyoung‐onset

Identifiers

PMID42680704
PMCPMC13533818

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