Integrative Single-Cell and Bulk Transcriptomic Analyses with Spatial Validation Identify a Residual Fatty Acid-EMT Subset Driving Chemotherapy Resistance in Triple-Negative Breast Cancer via MIF- and MK-Mediated Ligand-Receptor Signaling.

Zinab O Doha, Renad R Alharbi, Mohrah S Aljohani, Haneen M Alharbi, Hakeemah H Alnakhle, Ghadi S Alharbi, Shatha A Alerwi

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Article in International journal of molecular sciences, 2026. 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.

Tumor-Intrinsic DNA Damage Signaling Is Associated with MHC-I Expression and CD8 Cytotoxic T-Cell Engagement in Triple-Negative Breast Cancer.Current issues in molecular biology · 2026
Article

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

7 authors.

Zinab O DohaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.ORCID 0000-0003-2952-9840

Renad R AlharbiDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.

Mohrah S AljohaniDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.

Haneen M AlharbiDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.

Hakeemah H AlnakhleDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.ORCID 0000-0002-5311-7072

Ghadi S AlharbiDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.

Shatha A AlerwiDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.

Funding

Taibah University 447-16-1060

6 · The paper itself

Abstract

Chemotherapy resistance in triple-negative breast cancer (TNBC) remains a critical clinical challenge, with a substantial proportion of patients failing to achieve pathological complete response following neoadjuvant chemotherapy (NAC). Using an integrative single-cell RNA sequencing (scRNA-seq), bulk transcriptomic, and spatial proteomic framework, we aimed to identify the malignant epithelial subset driving this resistance and the intercellular signaling axes through which it reprograms the tumor microenvironment (TME). scRNA-seq analysis of NAC-treated breast tumors revealed a Fatty Acid-EMT co-expressing epithelial subset (FA-EMT) that is selectively enriched in the chemotherapy-resistant residuum. Critically, FA-EMT co-expression-rather than either program individually-most powerfully predicted chemotherapy resistance and reduced overall survival across two independent bulk transcriptomic cohorts comprising 277 TNBC patients (

Indexed as

Drug Resistance, NeoplasmFatty AcidsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceReceptors, CXCR4Signal TransductionSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisFatty AcidsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMIF protein, humanReceptors, CXCR4chemotherapy resistancefatty acid–EMT co-expressionMDK–NCLMIF–CD74–CXCR4single-cell RNA sequencingspatial proteomicsT-cell exhaustiontriple-negative breast cancertumor microenvironment

Identifiers

PMID42511503

DOI10.3390/ijms27146157

PMCPMC13409733

What OpenQuestion 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 OpenQuestion graph.