Epigenetic-related gene-based prognostic model construction and validation in prostate adenocarcinoma

Area of Science:

• Oncology
• Epigenetics
• Genomics

Background:

• Prostate adenocarcinoma (PRAD) is a prevalent cancer influenced by genetic and epigenetic factors.
• Understanding epigenetic alterations is crucial for improving PRAD diagnosis and treatment.

Purpose of the Study:

• To identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD.
• To investigate the prognostic value of ERGs and their role in disease progression.
• To explore the potential of an epigenetic scoring approach for PRAD patient stratification.

Main Methods:

• Utilized PRAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).
• Applied consensus clustering to identify prognosis-associated ERGs.
• Performed Gene Set Variation Analysis (GSVA) to assess pathway activities.
• Conducted experimental validation for key identified genes.

Main Results:

• Identified 13 differentially expressed ERGs with two distinct profiles in PRAD.
• Found significant pathway activity differences, notably in Hedgehog and Notch signaling.
• Established a correlation between higher epigenetic scores, favorable prognosis, and enhanced immunotherapeutic response.
• Validated the critical roles of CBX3 and KAT2A in PRAD progression.

Conclusions:

• Developed a novel epigenetic scoring approach as a promising prognostic tool for PRAD.
• CBX3 and KAT2A are identified as key molecular players in PRAD.
• Findings support the development of targeted and personalized PRAD treatment strategies.