Prognostic Implications of Nitrogen Metabolism-Related Gene SMS in Hepatocellular Carcinoma: An Integrated Bioinformatics and Experimental Research.
- 1Department of Hepatobiliary Surgery, Baoding No.1 Central Hospital, Baoding, Hebei, People's Republic of China.
- 2Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
- 3Graduate School, Chengde Medical University, Chengde, Hebei, People's Republic of China.
Abstract
Objective
To 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
Transcriptomic 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
Integrated 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
This 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.
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BibTeX
@article{gong2026prognostic,
title = {{Prognostic Implications of Nitrogen Metabolism-Related Gene SMS in Hepatocellular Carcinoma: An Integrated Bioinformatics and Experimental Research.}},
author = {Tianyi Gong and Ce Guo and Heng Wang and Xun Li and Hening Wang and Baojian Xing and Huiqing Zhang and Xiaolong Li},
journal = {Journal of hepatocellular carcinoma},
year = {2026},
month = oct,
doi = {10.2147/jhc.s638586},
url = {https://europepmc.org/article/MED/42921208},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Prognostic Implications of Nitrogen Metabolism-Related Gene SMS in Hepatocellular Carcinoma: An Integrated Bioinformatics and Experimental Research.
AU - Tianyi Gong
AU - Ce Guo
AU - Heng Wang
AU - Xun Li
AU - Hening Wang
AU - Baojian Xing
AU - Huiqing Zhang
AU - Xiaolong Li
PY - 2026
DA - 2026/10/19
JO - Journal of hepatocellular carcinoma
DO - 10.2147/jhc.s638586
UR - https://europepmc.org/article/MED/42921208
AB - Objective To 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 Transcriptomic 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 Integrated 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 This 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.
SN - 2253-5969
ER -