Significance of PFKFB4 and gene risk signature in cervical cancer prognosis and progression
Cervical cancer (CC) ranks among the most prevalent malignant gynecological neoplasms. Given the significant challenges in treating and detecting CC at an early stage, this study aims to identify key biomarkers associated with the prognosis and progression of this malignancy. Mendelian randomization (MR), expression quantitative trait locus (eQTL) data, survival assessments, and differential expression analyses were used to identify potential biomarkers. Based on the expression profiles of the identified genes, a risk signature was developed. The correlation between gene expression levels and the clinical characteristics of CC patients was also examined. Additionally, qRT-PCR, Transwell migration, and wound healing assays were conducted to validate the reliability of PFKFB4 expression, as well as cellular migration and invasion capabilities. The genes PFKFB4, SFXN3, and ITGB2 were identified as critical targets for CC. MR analysis revealed that ITGB2 and PFKFB4 exhibited a negative correlation with CC development, whereas SFXN3 demonstrated a positive association with the disease. Mechanistic investigations highlighted a strong link between these genes and the immune microenvironment. The developed risk signature displayed significant correlations with the prognosis, metastatic stages, and histological classifications of CC patients. Furthermore, the expression level of PFKFB4 was significantly associated with the T and M stages in CC patients. Notably, PFKFB4 was significantly overexpressed in cervical cancer cells and tissue samples, and its silencing markedly inhibited cell migration and invasion. In summary, this study elucidates the molecular mechanisms underlying CC progression and identifies potential candidate biomarkers that could inform treatment strategies for this malignancy.