Evidence mapPaperPMID 42478154Full record

ArticleChemical biology & drug design2026

An Integrative Methylation-Metabolism Gene Signature Defines Prognosis and Immunosuppressive Microenvironment in Prostate Cancer.

Chao Zhang, Likun Liu, Kai Wu

Abstract read
In one paragraph

Article in Chemical biology & drug design, 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

What it found

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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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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

3 authors.

Chao ZhangDepartment of Urology, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
Likun LiuDepartment of Oncology, Shanxi Traditional Chinese Medical Hospital, Taiyuan, China.ORCID https://orcid.org/0000-0002-7016-7530
Kai WuDepartment of Urology, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

Funding

Four"Batches"Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province program 2023XM050Science and Education Cultivation Fund of the National Cancer and Regional Medical Center of Shanxi Provincial Cancer Hospital QH2023044Science and Technology of Shanxi Province program 2025ZYYB059
6 · The paper itself

Abstract

The synergistic crosstalk between epigenetic dysregulation and metabolic reprogramming underlies to prostate cancer (PCa) development and treatment resistance, yet an integrated prognostic signature reflecting this nexus remains poorly defined. We developed and validated a gene signature associated with methylation and amino acid metabolism for patient stratification and exploring its connection to tumor microenvironment (TME) remodeling. RNA sequencing data and independent datasets were integrated with predefined gene sets for DNA methylation (n = 79) and amino acid metabolism (n = 471). A analytical workflow was employed: identification of hub genes and least absolute shrinkage and selection operator (LASSO)-Cox modeling; construction of a prognostic nomogram; comprehensive TME profiling; and validation through single-cell RNA sequencing (scRNA-seq) cellular dynamics analysis and immunohistochemistry (IHC) on a prostate cancer tissue microarray. A novel six-gene prognostic model (ASPM, WDR86, CCK, HOXA2, EGF, ZFHX4) was developed. This model efficiently discriminates patients into groups based on risk level though divergent overall survival (p < 0.001) and exhibited high predictive accuracy in external validation sets (3-year area under the curve (AUC) = 0.87). A nomogram incorporating the signature, pathologic T stage, and Gleason score surpassed individual clinical factors (5-year AUC = 0.73). Functional annotation indicated that high-risk tumors were characterized by downregulated androgen response and activated E2F/G2M checkpoint pathways. The signature was correlated with an immunosuppressive TME, which was supported by a negative correlation between ZFHX4 and monocyte infiltration (r = -0.37, p < 0.001) and a positive correlation between ASPM and activated CD4

Indexed as

DNA MethylationProstatic NeoplasmsTumor MicroenvironmentAmino AcidsGene Expression Regulation, NeoplasticHumansMalePrognosisAmino Acidsamino acid metabolismbiomarker validationDNA methylationimmunotherapyprognostic signatureprostate cancertumor microenvironment

Identifiers

PMID42478154
PMCPMC13386026

What Socratic holds

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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 Socratic graph.