Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Aberrant DNA methylation is implicated in differentiated thyroid cancer (DTC) tumorigenesis.
• Factors contributing to DTC local and regional recurrence remain incompletely understood.

Purpose of the Study:

• To investigate the association between DNA methylation-driven genes and DTC recurrence.
• To identify specific genes linked to DTC recurrence through methylation analysis.

Main Methods:

• Utilized RNA sequencing and DNA methylation data from The Cancer Genome Atlas (TCGA) for DTC.
• Applied methylmix R package and Cox regression analyses to identify prognosis-related methylation-driven genes.
• Correlated gene expression with clinicopathological features and functional pathways.

Main Results:

• Identified 168 differentially expressed methylation-driven genes in thyroid cancer, with 10 identified as hub genes.
• PLAU was significantly upregulated in DTC and strongly correlated with recurrence risk (p < 0.05).
• PLAU expression linked to immune signaling pathways, neutrophil, and dendritic cell markers; two methylation sites (cg06829584, cg19399285) associated with PLAU expression.

Conclusions:

• The methylation-driven gene PLAU is an independent risk factor for DTC recurrence.
• PLAU functions as an oncogene by regulating immune-related signaling pathways.
• Findings offer insights into thyroid cancer mechanisms and potential for personalized treatment.