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Updated: Jul 1, 2025
Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
Published on: October 11, 2018
Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through
Fanli Bu1, Xiao Qin1, Tiantian Wang1
1Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, 257091, People's Republic of China.
Insights
This study identifies four pyrimidine metabolism genes (PyMGs), including NT5C2 and RRM1, as key players in atherosclerosis (AS) pathogenesis. These findings offer potential new biomarkers for AS monitoring and therapeutic strategies.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Research
Background:
- Atherosclerosis (AS) is a major cardiovascular disease driven by chronic inflammation and metabolic dysregulation.
- Pyrimidine metabolism (PyM) plays a critical role in cellular processes, but its specific involvement in AS is not well understood.
- Identifying pyrimidine metabolism genes (PyMGs) linked to AS is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify and validate pyrimidine metabolism genes (PyMGs) associated with atherosclerosis (AS).
- To explore the diagnostic potential and clinical relevance of identified PyMGs in AS.
- To elucidate the role of PyMGs in AS pathogenesis and potential therapeutic interventions.
Main Methods:
- Bioinformatic analysis of 41 candidate PyMGs using differential expression analysis.
- Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to identify biological pathways.
- Lasso regression and SVM-RFE for gene selection and diagnostic assessment, validated with public datasets.
Main Results:
- Four PyMGs were identified as significantly associated with AS, with NT5C2 and RRM1 highlighted as key genes.
- Functional enrichment analysis revealed PyMGs' involvement in pyrimidine metabolism and nucleotide biosynthesis.
- The selected PyMGs demonstrated promising diagnostic potential for distinguishing AS.
Conclusions:
- This study identifies four PyMGs, including NT5C2 and RRM1, as potential contributors to AS pathogenesis.
- These genes represent novel biomarkers for AS monitoring and progression.
- The findings open new avenues for therapeutic strategies targeting pyrimidine metabolism in atherosclerosis.
Background:
This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS.
Methods:
A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets.
Results:
This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results.
Conclusion:
In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.
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