Evidence map›Paper›PMID 41258556›Full record

ArticleDiscover oncology2025

NAP1L4 in hepatocellular carcinoma progression and treatment from gene expression to clinical impact.

Junjie Lin, Hehe Yin, Zihan Xie, Meihui Liu, Lulu Kong, Ruixuan Yao, Guang Chen, Yuyao Li, Jiaojiao Shen, Qingling Wang and 3 more

Abstract read
In one paragraph

Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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

13 authors.

Junjie Lin *Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Hehe Yin *Anhui Province Key Laboratory of Infectious Diseases, Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Zihan XieDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Meihui LiuDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Lulu KongDepartment of Hematology, Xuzhou Medical University, No.209 Tongshan Road, Xuzhou, 221004, China.
Ruixuan YaoDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Guang ChenDepartment of Nephrology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Yuyao LiDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Jiaojiao ShenDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Qingling WangAnhui Province Key Laboratory of Infectious Diseases, Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Kexing HanDepartment of Respiratory Medicine, Bengbu Medical University, No. 2600, Donghai Avenue, Bengbu, 233030, China.
Honghai XuDepartment of Pathology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China.
Yufeng GaoDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230031, China. gaoyufeng0917@126.com.

Funding

Anhui Provincial Special Fund for Clinical Medical Research Transformation No.202304295107020040National Natural Science Foundation of China No. 82370608Natural Science Foundation of Anhui Province No.2208085MH204Natural Science Foundation of Education Department of Anhui Province No. 2022AH040160
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) remains one of the deadliest malignancies globally, posing substantial health threats and economic burdens. Despite advances in therapeutic modalities-including surgical resection, liver transplantation, and targeted therapies-HCC prognosis remains unsatisfactory. This highlights an urgent need for novel biomarkers to improve prognostic stratification. Senescence-related genes (SRGs) have emerged as promising candidates for HCC prognostic exploration, making their association with clinical outcomes the focus of this study.​.

methodsComprehensive machine learning was applied to screen SRGs associated with HCC survival, identifying key prognostic genes. A clinical nomogram based on SRG scores was constructed and validated. NAP1L4 expression in HCC was verified using GEPIA2.0, UALCAN, HPA databases, and clinical samples from 40 patients at the First Affiliated Hospital of Anhui Medical University. In vitro, NAP1L4 was knocked down in HCCLM3 cells to assess proliferation and migration changes. RNA-seq analyzed differentially expressed genes post-knockdown, followed by GSEA/KEGG enrichment to identify relevant pathways. Drug sensitivity and Mendelian randomization analyses explored therapeutic implications and gut microbiota-related HCC risk modulation.​.

resultsMachine learning identified NAP1L4 as a pivotal SRG, with the SRG score-based nomogram strongly associated with poor overall survival. High NAP1L4 expression in HCC was confirmed by multi-omics and clinical samples. NAP1L4 knockdown in HCCLM3 cells significantly inhibited proliferation and migration. RNA-seq revealed 129 upregulated and 101 downregulated genes post-knockdown, with GSEA/KEGG highlighting the NOD-like receptor pathway as critical for NAP1L4-mediated HCC effects. Elevated NAP1L4 correlated with adverse prognosis and tumor microenvironment alterations (increased M0 macrophages and regulatory T cells). Reduced NAP1L4 expression enhanced sensitivity to cisplatin and axitinib. Mendelian randomization showed ANGPT1 modulates HCC risk by increasing gut Faecalitalea cylindroides abundance.​.

conclusionSRGs, particularly NAP1L4, play critical roles in HCC progression. High NAP1L4 expression associates with poor prognosis, tumor microenvironment remodeling, and altered drug sensitivity. These findings support SRGs as potential prognostic biomarkers and therapeutic targets to enhance HCC treatment efficacy.

Indexed as

Gut microbiotaHepatocellular carcinomaMachine learningNAP1L4Senescence

Identifiers

PMID41258556
PMCPMC12708435

What Socratic holds

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LicenceCC BY-NC-ND
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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.