{
  "abstract": "Objective\n\nTo identify nitrogen metabolism-related genes associated with hepatocellular carcinoma (HCC) prognosis, focusing on spermine synthase (SMS), and to evaluate its prognostic and risk-stratification value.Methods\n\nTranscriptomic and clinical data from TCGA-LIHC and GSE14520 and single-cell RNA-sequencing data from GSE242889 were analyzed. Prognostic genes were screened using univariate Cox, LASSO-Cox, and random survival forest analyses. The prioritized candidate, SMS, was subsequently evaluated by immunohistochemistry in an independent cohort of 144 patients with HCC after curative resection. Associations with clinicopathological features, recurrence-free survival (RFS), and overall survival (OS) were assessed. Prognostic models were evaluated using time-dependent ROC analysis, and risk stratification was examined by combining SMS expression with microvascular invasion (MVI) status and Barcelona Clinic Liver Cancer (BCLC) stage.Results\n\nIntegrated bioinformatics and machine-learning analyses prioritized SMS, a key enzyme in polyamine biosynthesis, as the top-ranked nitrogen metabolism-related prognostic candidate, and its prognostic association was validated in GSE14520. In the clinical cohort, high SMS expression was significantly associated with multiple tumors, MVI positivity, and BCLC stage B/C. High SMS expression was also associated with shorter RFS and OS and remained independently associated with unfavorable RFS and OS in multivariable Cox analyses. The combined clinical+SMS model showed better prognostic discrimination than the SMS-only model, whereas its improvement over the clinical model was not statistically significant. Combined stratification showed particularly unfavorable outcomes in patients with high SMS expression and MVI positivity, while SMS further differentiated prognosis within the BCLC A and BCLC B/C subgroups.Conclusion\n\nThis study provides independent clinical validation of the prognostic relevance of SMS in HCC. High SMS expression was associated with aggressive clinicopathological features and unfavorable postoperative outcomes. Integrating SMS expression with MVI status and BCLC stage may provide complementary information for postoperative risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary Surgery, Baoding No.1 Central Hospital, Baoding, Hebei, People's Republic of China.",
    "Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.",
    "Graduate School, Chengde Medical University, Chengde, Hebei, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianyi Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Ce Guo"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Heng Wang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Xun Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hening Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Baojian Xing"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiqing Zhang",
      "orcid": "0000-0002-9137-9671"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaolong Li",
      "orcid": "0009-0000-9840-3569"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d05rfps5tvc8t.bib",
  "cited_by": 0,
  "doi": "10.2147/jhc.s638586",
  "fulltext_url": "https://europepmc.org/articles/PMC13693530",
  "id": "d05rfps5tvc8t",
  "issns": [
    "2253-5969"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921208",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2721|Hepatocellular Carcinoma Treatment and Prognosis"
    ]
  ],
  "openalex": "W7222879699",
  "pdf_url": "https://europepmc.org/articles/PMC13693530?pdf=render",
  "pmcid": "PMC13693530",
  "pmid": "42921208",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d05rfps5tvc8t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42921208",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921208"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Hepatocellular Carcinoma Treatment and Prognosis",
      "subfield": "general"
    }
  ],
  "title": "Prognostic Implications of Nitrogen Metabolism-Related Gene SMS in Hepatocellular Carcinoma: An Integrated Bioinformatics and Experimental Research.",
  "title_text": "Prognostic Implications of Nitrogen Metabolism-Related Gene SMS in Hepatocellular Carcinoma: An Integrated Bioinformatics and Experimental Research.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/d05rfps5tvc8t",
  "venue": "Journal of hepatocellular carcinoma",
  "versions": []
}