ArticleCombinatorial chemistry & high throughput screening2025
Identifying the Crucial Biomarker of MASH-Related HCC.
Article in Combinatorial chemistry & high throughput screening, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- THBS2 as a Key Regulator in Gastrointestinal Tumors: from Molecular Mechanisms to Clinical Applications.Current oncology reports · 2026Review
- The role of SPP1 in evaluating the prognosis, immune infiltration, and drug sensitivity of hepatocellular carcinoma.PloS one · 2026Article
- RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.Journal of Cancer · 2026Article
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Authors and funding
8 authors.
Funding
Abstract
objectivesThis study aimed to explore the key oncogenic factor of metabolicassociated steatohepatitis (MASH) to hepatocellular carcinoma (HCC).
methodsWe utilized four differential GEO datasets (GSE164760, GSE139602, GSE197112, and GSE49541) to identify the key oncogenic factor for MASH-related HCC. The differential genes were analyzed using the GEO2R algorithm online. The GEPIA online website was used to explore the expression of selected four genes (SPP1, GNMT, CLDN11, and THBS2). The genetic alterations in genes were estimated by the cBioPortal website. The Kaplan-Meier Plotter online database was applied to explore the prognostic value of SPP1. Univariate and multivariate Cox analyses were carried out to further confirm the prognostic value of SPP1. The GO and KEGG enrichment analysis exported associated pathways with SPP1 expression. The positively or negatively related immune cells and immune checkpoint expressions were identified through Pearson correlation analysis. The lipogenesis-associated proteins were detected using western blotting and fluorescence. The high-fat diet (HFD) mouse model was constructed, and liver samples were collected.
resultsSPP1, GNMT, CLDN11, and THBS2 were determined in the transformation process of MASH to liver fibrosis. SPP1 and GNMT were upregulated in the HCC tumor tissue. SPP1, in particular, had the potential to be the prognostic factor through Cox analysis. Remarkably, SPP1 was highly expressed in HCC compared to normal tissues in three independent datasets (GSE121248, GSE14520, and GSE45267). SPP1 is mainly involved in the amplification and deep deletion mutations. SPP1 was found to be strongly correlated with ANXA2 expression, and ANXA2 was also highly expressed in HCC with significant prognostic performance. Moreover, SPP1 was found to participate in the carcinogenic mechanism and correlate with immune cells and immune checkpoint expression. SPP1 knockdown suppressed the SREBP1 and FASN expressions and increased the SIRT1 expression
conclusionSPP1 may be the key oncogenic factor for the transformation of MASH to HCC, and it could be a potential immunotherapeutic target in HCC.
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