Fatty acid metabolism-related signature suggests an oncogenic role of FASN in cervical cancer.

BACKGROUND

The metabolism of fatty acids is essential in the initiation and progression of cervical cancer. The objective of this research is to develop a prognostic model associated with fatty acid metabolism and to identify the FASN protein within this framework, with the intention of investigating its function in cervical squamous cell carcinoma (CESC) and its correlation with patient prognosis.

METHODS

This prognostic model was developed using least absolute shrinkage and selection operator (LASSO) regression analysis on the training cohort derived from The Cancer Genome Atlas (TCGA) dataset. A nomogram for overall survival (OS) was effectively constructed by integrating the model risk scores with clinical characteristics. Furthermore, we analyzed various correlations involving pathway enrichment, therapeutic approaches, immune cell infiltration, and the prognostic model itself. The functional significance of the FASN gene was examined through Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). In addition, we performed an in-depth assessment of the correlation between FASN expression and various clinical parameters sourced from the TCGA database, which encompassed tumor (T), node (N), and metastasis (M) stages, age, weight, and histological grade. Utilizing the "rms" R package, we constructed a nomogram model that combines clinical attributes with levels of FASN expression. Moreover, immunohistochemical analyses were performed to evaluate FASN expression in a cohort of 30 cases diagnosed with cervical cancer.

RESULTS

We developed a prognostic model that includes eight genes: FASN, ACAT2, HMGCS1, IL4I1, ACAA2, SERINC1, CEL, and TP53INP2. The association between the altered expression of these genes and patient survival outcomes was confirmed through Kaplan-Meier survival analysis. Both univariate and multivariate Cox regression analyses revealed that FASN functions as an independent prognostic factor for OS within the TCGA cohort. Increased expression of FASN was associated with advanced T and N stages, higher clinical stages, older age, lower weight, greater histological grades, and a poorer prognosis. A nomogram was developed that integrates FASN expression with clinical variables to predict the likelihood of OS for patients at 1, 3, and 5 years. Additionally, immunohistochemical analysis indicated that FASN expression was significantly elevated in cervical cancer tissues when compared to adjacent non-cancerous tissues in a study involving 30 patients.

CONCLUSIONS

This study clarified a specific signature associated with fatty acid metabolism, specifically FASN, which is connected to both the initiation and progression of CESC. Furthermore, FASN may serve as a prognostic marker for individuals diagnosed with CESC, thus providing fresh insights for the formulation of clinical treatment strategies.