Evidence map›Paper›PMID 41126211›Full record

ArticleCancer cell international2025

Comprehensive phosphoproteomic profiling reveals sex-specific regulatory mechanisms in HrasG12V-driven hepatocarcinogenesis.

Changcheng Yang, Juefu Hu, Liang Yao, Yang Yu, Xiaoying Dong, Jun Chen, Aiguo Wang, Huiling Li

Abstract read
In one paragraph

Article in Cancer cell international, 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

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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

1 citing paper in PubMed.

  1. Aflatoxin BJournal of fungi (Basel, Switzerland) · 2026
    Article
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

8 authors.

Changcheng Yang *Department of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Juefu Hu *Department of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Liang YaoDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Yang YuDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Xiaoying DongDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Jun ChenDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China.
Aiguo WangDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China. wangaiguo@dmu.edu.cn.
Huiling LiDepartment of Comparative Medicine, Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning, China. lhl@dmu.edu.cn.

Funding

National Natural Science Foundation of China 30872950
6 · The paper itself

Abstract

objectiveTo identify common and sex-specific phosphorylation dynamics during hepatocarcinogenesis in HrasG12V transgenic mice (Hras-Tg).

methodsWe constructed a phosphoproteomic database using male/female (M/F) tumor (T), precancerous (P), and wild-type liver tissues (W) from Hras-Tg, validated via parallel reaction monitoring (PRM). Comparative analysis and hierarchical clustering were employed to delineate shared and sex-stratified phosphorylation signatures in hepatocellular carcinoma (HCC) development.

resultsPRM-validated phosphoproteomic profiling quantified 5,410 phosphorylation sites across 2,427 proteins. Analysis of common features revealed nuclear-enriched phosphoprotein accumulation in tumors versus precancerous/wild-type tissues (T vs. P/W). KEGG pathway analysis identified consistently dysregulated pathways including MAPK signaling, focal adhesion, and protein digestion/absorption. Protein-protein interaction (PPI) network analysis of shared phosphoproteins pinpointed key regulators (Alb, Hspa5, Psn), with high connectivity, suggesting potential regulatory roles in the network. Sex-specific analyses demonstrated distinct phosphorylation patterns: males exhibited extensive membrane protein phosphorylation alterations, while females showed predominant cytoplasmic modifications. KEGG pathway mapping revealed male-biased dysregulation in Ras signaling, mTOR pathways, and actin cytoskeleton regulation. Functional annotation indicated greater complexity of phosphorylated proteins in males. Notably, phosphorylation events occurring on proteins with annotated kinase or phosphatase activity were more prevalent in males, suggesting enhanced phosphorylation-mediated signaling dynamics. SIGNIFICANCE: This study establishes the first sexual dimorphism-aware phosphoproteomic resource for Ras-driven hepatocarcinogenesis, systematically characterizing conserved and sex-divergent phosphorylation networks. The findings provide preliminary molecular insights into gender disparities in HCC progression and may guide future therapeutic exploration.

Indexed as

Hepatocellular carcinomaPhosphoproteomicsRas oncogeneSexual dimorphismSignaling pathways

Identifiers

PMID41126211
PMCPMC12542278

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