Evidence map›Paper›PMID 41406083›Full record

ArticleScience progress

Lactate metabolism orchestrates immune dysregulation in renal cancer: A multi-omics and causal inference study.

Jiangbo Li, Chen Liu, Zhiguang Fu, Qi He, Xu Liu, Zhijia Sun

Abstract read
In one paragraph

Article in Science progress. 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Jiangbo LiBioinformatics Center of AMMS, Beijing, China.
Chen LiuDepartment of Radiation Oncology, Air Force Characteristic Medical Center, Air Force Medical University, Beijing, China.
Zhiguang FuDepartment of Radiation Oncology, Air Force Characteristic Medical Center, Air Force Medical University, Beijing, China.
Qi HeBioinformatics Center of AMMS, Beijing, China.
Xu LiuDepartment of Radiation Oncology, Air Force Characteristic Medical Center, Air Force Medical University, Beijing, China.
Zhijia SunDepartment of Radiation Oncology, Air Force Characteristic Medical Center, Air Force Medical University, Beijing, China.ORCID 0000-0001-6608-2326

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BackgroundLactate shapes the tumor microenvironment and modulates immunity. Investigating lactate metabolism genes in renal cell carcinoma (RCC) could elucidate therapeutic targets.MethodsSingle-cell RNA sequencing (GSE242299), bulk RNA sequencing (GSE102101), and spatial transcriptomics (GSE175540) data for RCC were retrieved from GEO. Data processing included quality control, normalization, and dimensionality reduction (R packages). RCTD and CellChat were used for spatial deconvolution and cell-cell communication analysis. CIBERSORT and GSEA evaluated immune infiltration and pathway enrichment. Lactylation scores were derived via single-sample gene set enrichment analysis (ssGSEA) of lactate metabolism genes. Mendelian randomization (MR) assessed gene-cancer risk associations.ResultsMacrophages demonstrated a higher potential for interactions with other cell types due to their extensive receptor-ligand relationships. Lactylation score and MR analysis identified six pivotal genes associated with renal cancer risk: C4A and SERPINA1 were correlated with an elevated disease risk, whereas CD70, FXYD2, SERPINE1, and TUBB6 were associated with a reduced risk. These genes are linked to the degree of immune cell infiltration and can influence the disease process through diverse mechanisms. We also explored the expression profiles of primary genes involved in lactate metabolism in RCC and compared the metabolic pathways between different groups. Notably, experimental validation via tissue microarray immunofluorescence confirmed that the risk-associated genes C4A and SERPINA1 were significantly overexpressed in RCC tumor tissues.ConclusionLactic acid metabolism regulates RCC progression by modulating metabolic activity and immune cell infiltration. Key lactate metabolism genes present novel targets for RCC treatment.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsLactic AcidGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMendelian Randomization AnalysisMultiomicsTranscriptomeTumor MicroenvironmentLactic Acidimmune cell infiltrationlactic acid metabolismMendelian randomizationRenal cell carcinomaspatial transcriptome

Identifiers

PMID41406083
PMCPMC12712302

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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.