Evidence mapPaperPMID 42401103Full record

ArticleTranslational oncology2026

Single-cell spatial landscape of aggrephagy activity stratifies hepatocellular carcinoma neutrophils and delivers a 5-gene diagnostic panel for patient stratification.

Wanju Jiang, Kai Wang, Guoshu Li, Qiqi Zhang

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Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Wanju JiangDepartment of General Surgery, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
Kai WangDepartment of Pulmonary Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.
Guoshu LiDepartment of Pulmonary Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China. Electronic address: guoshuli7028@163.com.
Qiqi ZhangDepartment of Hepatopancreatobiliary Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. Electronic address: zqqtongji@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (LIHC) features a complex tumor microenvironment (TME) where tumor-associated neutrophils (TANs) show significant plasticity. The role of aggrephagy-selective autophagy of protein aggregates-in shaping neutrophil heterogeneity and LIHC progression remains poorly understood.

methodsWe integrated scRNA-seq (183,671 cells), spatial transcriptomics, and bulk datasets (TCGA, GSE39791). Neutrophils (n=12,547) were re-clustered into six subsets, and aggrephagy activity was quantified via UCell scores. Analysis included pseudotime trajectories, cell-cell communication, metabolic scoring, and machine-learning-based feature selection, followed by in vitro functional validation.

resultsAggrephagy activity was significantly elevated in tumor tissues compared with adjacent normal tissues (P < 0.001) and showed strong cell-type specificity, with TANs among the most enriched populations. High-aggrephagy neutrophils exhibited an undifferentiated state, preferential tumor enrichment, and a positive correlation with transcriptomic risk scores. Trajectory analysis positioned these cells at an early differentiation branch and revealed dominant neutrophil-to-stroma signaling through the CCL3-CCR1, SPP1-CD44, and ANXA1-FPR1 axes. Metabolically, high-aggrephagy neutrophils displayed enhanced inflammatory and epithelial mesenchymal-transition programs alongside suppressed oxidative phosphorylation. Integrative network analysis identified a five-gene diagnostic panel (SQSTM1, WDFY3, DOCK4, CD177, LIMK2) with robust performance across bulk cohorts (AUC 0.83-0.91). Among these, LIMK2 marked a highly interactive neutrophil subset and functionally promoted tumor cell proliferation, survival, migration, and invasion in vitro.

conclusionAggrephagy is associated with a pro-tumorigenic, metabolically reprogrammed neutrophil state in LIHC. The LIMK2-centered gene panel provides a robust framework for subset identification and nominates candidate targets for future autophagy- and neutrophil-directed studies.

Indexed as

AggrephagyHepatocellular carcinomaImmunotherapyTumor-associated neutrophilsTumor microenvironment

Identifiers

PMID42401103
PMCPMC13348072

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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.