A novel 5-differentially expressed gene (DEG) signature predicting the prognosis in patients with metastatic liver malignancies and the prognostic and therapeutic potential of SPP1.

Jing Liu, Zijian Yu, Qiong Liu, Chengyun Dou, Peng Cao, Xia Xie

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Article in International journal of clinical oncology, 2025. 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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1 citing paper in PubMed.

Convergent Immune-Coagulation Programs Underlie Gastrointestinal Bleeding Risk in Portal Vein Tumor Thrombosis-Associated Hepatocellular Carcinoma and Portal Hypertension.Human mutation · 2026
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6 authors.

Jing LiuDepartment of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Zijian YuDepartment of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Qiong LiuDepartment of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Chengyun DouDepartment of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Peng CaoDepartment of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. doctorcp20161225@126.com.

Xia XieDepartment of Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. xiexia1109@sina.com.

Funding

Health Commission of Hunan Province 202103080306Natural Science Foundation of Hunan Province 2022JJ40398

6 · The paper itself

Abstract

backgroundThis study aimed to identify differentially expressed genes (DEGs) that are associated with hepatocarcinogenesis and metastasis in hepatocellular carcinoma (HCC) and to explore their value in predicting overall survival (OS). The methods used included bioinformatics analysis of gene expression datasets and in vitro experiments using HCC cell lines.

methodsGene expression profiles from metastatic and non-metastatic liver cancer specimens were analyzed using the limma R package. Functional enrichment was performed using Metascape. A prognostic 5-gene signature was constructed using the LASSO algorithm based on TCGA-LIHC data. Kaplan-Meier survival analysis assessed the association of these genes with clinical outcomes (DFI, DSS, OS, and PFS). In vitro, Huh7 and Hep3B cells were transfected with shRNA for SPP1 knockdown. Cell viability was measured with CCK-8 assays, and migration was assessed with Transwell and wound-healing assays. Protein expression was evaluated via western blotting.

resultsThe analysis of gene expression profiles led to the identification of 11 DEGs associated with immune response, phagocytosis, and cell migration. From these DEGs, the LASSO algorithm identified a 5-DEG signature (MASP1, MASP2, MUC1, TREM1, and SPP1) that was predictive of OS in liver cancer patients. Among the five genes, SPP1 was the most upregulated in cancer samples and was significantly associated with poorer outcomes, including DFI, DSS, OS, and PFS. In vitro experiments confirmed that SPP1 knockdown in Huh7 and Hep3B cells significantly inhibited cancer cell viability and migration. Western blot analysis showed alterations in key proteins, with a reduction in vimentin and Ki-67 and an increase in E-cadherin following SPP1 knockdown.

conclusionThis study highlights the pivotal effect of SPP1 on HCC development and underscores its potential as a biomarker for the OS of liver cancer patients. The identified DEGs may serve as predictive markers for OS and potential therapeutic targets for HCC treatment.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularLiver NeoplasmsOsteopontinCell Line, TumorCell MovementFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMalePrognosisTranscriptomeBiomarkers, TumorOsteopontinSPP1 protein, human5-DEG signatureIntegrative bioinformatics analysesLASSO algorithmLiver cancerMetastasisSecreted phosphoprotein 1 (SPP1)

Identifiers

PMID40014188

DOI10.1038/nrm3758

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