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Association between pathologic factors and ERG expression in prostate cancer: finding pivotal networking
Seung-Ryeol Lee1,2, Young-Deuk Choi3, Nam-Hoon Cho4
1Department of Urology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam, South Korea.
Journal of Cancer Research and Clinical Oncology
|June 28, 2018
Summary
Erythroblast transformation-specific (ETS)-related gene (ERG) positivity in prostate cancer is associated with perineural invasion and higher Gleason scores. NOTCH1 was identified as a key gene in the ERG regulatory network, suggesting its clinical significance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer is a significant health concern, and understanding its molecular underpinnings is crucial for improved diagnostics and therapeutics.
- Erythroblast transformation-specific (ETS)-related gene (ERG) expression is a known biomarker in prostate cancer, but its precise associations with pathological features and regulatory pathways require further elucidation.
Purpose of the Study:
- To investigate the correlation between pathological factors and ETS-related gene (ERG) expression in prostate cancer.
- To identify target genes and regulatory networks associated with ERG expression using next-generation sequencing.
Main Methods:
- Utilized association rule mining (Apriori algorithm) to compare ERG expression with pathological findings in 60 radical prostatectomies.
- Performed whole-exome and RNA sequencing on ERG-positive and negative prostate cancer samples.
- Constructed a gene regulatory network using Cytoscape and the GeneMANIA plugin to identify pivotal genes.
Main Results:
- ERG positivity was significantly associated with perineural invasion, apical margins, and Gleason score 3+4=7 (p=0.0008).
- Whole-exome and RNA sequencing revealed 97 somatic mutations, with NOTCH1, MEF2C, STAT3, and LCK identified as key regulatory genes.
- NOTCH1 was identified as a central hub in the regulatory network and showed a significant association with ERG positivity (p=0.001).
Conclusions:
- The study establishes a link between ERG expression and specific pathological indicators in prostate cancer, including perineural invasion and Gleason score.
- Identification of NOTCH1 as a critical node in the ERG regulatory network provides insights into the molecular mechanisms driving ERG-positive prostate cancer.
- Further evaluation of ERG expression and its associated regulatory network may enhance the understanding of prostate cancer's clinical significance.
Keywords:
ERG (ETS-related gene)ETS (erythroblast transformation-specific) gene fusionsNext-generation sequencingProstate cancerTMPRSS2 (transmembrane protease serine 2 gene)More Related Videos
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