Phosphoinositide metabolism-related prognostic genes and their prognostic value in cervical cancer: an investigation based on transcriptome, single-cell analyses and verification.
TL;DR
The risk model and nomogram aided prognosis prediction, providing new insights for CESC treatment and VAC14 and INPP5K were PPM-related prognostic genes for CESC.
Abstract
Background
Cervical cancer (CESC) is a major gynecological malignancy, and abnormalities in phosphoinositide metabolism (PPM) are closely linked to tumor progression. This study aimed to screen phosphoinositide metabolism-related genes (PPM-RGs) with prognostic value for CESC and explore their molecular mechanisms and clinical significance.
Methods
CESC transcriptomic datasets and PPM-RGs were retrieved from public databases. Differentially expressed genes were intersected with PPM-RGs to obtain candidate genes. Prognostic genes were screened via univariate Cox regression and proportional hazards assumption test, and a risk model was constructed using random survival forest (RSF). Independent prognostic analysis and nomogram establishment were performed, followed by pathway enrichment, immune infiltration, somatic mutation and single-cell analyses to characterize the tumor microenvironment. Immunohistochemical staining was used to verify the protein expression of key genes in CESC tissues.
Results
Twenty candidate genes were initially identified, and two protective prognostic genes VAC14 and INPP5K were finally determined. The risk model showed favorable predictive performance with area under the curve (AUC) over 0.7, and high-risk patients had poorer survival. The nomogram combining risk score and M stage presented high accuracy. The high-risk group exhibited distinct pathway enrichment, altered immune infiltration and low somatic mutation rates. Monocytes were identified as potential key cells with impaired communication and differentiation in CESC. Immunohistochemistry confirmed downregulated expression of the two genes in CESC epithelial cells.
Conclusion
VAC14 and INPP5K were PPM-related prognostic genes for CESC. Monocytes played critical roles in CESC progression. The risk model and nomogram aided prognosis prediction, providing new insights for CESC treatment.