Evidence map›Paper›PMID 41601657›Full record

ArticleFrontiers in immunology2025

Integrated multi-omic profiling reveals macrophage-driven prognostic signatures in clear cell renal cell carcinoma through machine learning optimization.

Wei Cao, Wenyuan Zhuang, Kai Xu

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

1 citing paper in PubMed.

  1. 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

3 authors.

Wei CaoDepartment of Urology, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
Wenyuan ZhuangDepartment of Urology, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
Kai XuDepartment of Urology, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Clear cell renal cell carcinoma (KIRC) is the most prevalent and aggressive form of kidney cancer, with limited survival despite advances in combination immunotherapy. Tumor-associated macrophages (TAMs) critically shape the tumor microenvironment (TME) and influence treatment resistance. We aimed to delineate TAM heterogeneity, identify prognostic macrophage signatures, and characterize the immune-metabolic programs underpinning KIRC progression. Methods: We integrated single-cell RNA sequencing (scRNA-seq) data from ten KIRC tumors with high-dimensional weighted gene co-expression network analysis (hdWGCNA) and twenty machine-learning models. Five macrophage subpopulations were defined by canonical markers and validated spatially. A macrophage-centric prognostic signature was trained using a random survival forest model and validated in another independent cohort. We further interrogated mutational landscapes, immune-stromal infiltration (xCell), pathway activation (ssGSEA), and clinical correlations. Results: scRNA-seq identified five transcriptionally distinct macrophage (Mac) subsets, including three lipid-associated Mac populations (LA-Mac: ALOX5AP+LA-Mac, HERPUD1+LA-Mac, and PRDX1+LA-Mac), an FCN1+inflammatory Mac subset (FCN1+Inflam-Mac), and an oxidative phosphorylation-enriched subset (OxP-Mac), distinct from canonical M1/M2 signatures. hdWGCNA revealed ten co-expression modules, among which the Mac-M2 module demonstrated the highest macrophage specificity and was preferentially enriched in tumor tissues. Based on seven hub genes from the Mac-M2 module, RSF model was constructed, achieving robust prognostic performance and effectively stratifying patients into high- and low-risk groups (log-rank Conclusion: This multi-omics study illuminates the transcriptional and functional heterogeneity of TAMs in KIRC and establishes a macrophage-derived prognostic signature with translational potential. Our findings underscore the dual roles of macrophage polarization in mediating immune suppression and metabolic adaptation, offering novel targets for clinical diagnosis and treatment of KIRC.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsMachine LearningMacrophagesTumor-Associated MacrophagesBiomarkers, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMultiomicsPrognosisSingle-Cell Gene Expression AnalysisTumor MicroenvironmentBiomarkers, Tumorclear cell renal cell carcinoma (KIRC)high-dimensional weighted gene co-expression network analysis (hdWGCNA)machine learningprognostic biomarkerssingle-cell RNA sequencing (scRNA-seq)tumor-associated macrophages (TAMs)tumor microenvironment (TME)

Identifiers

PMID41601657
PMCPMC12833068

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.