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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in
Caterina Peraldo-Neia1, Giorgia Migliardi, Maurizia Mello-Grand
1Department of Clinical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy. caterina.peraldoneia@ircc.it
Background:
Activating mutations of the epidermal growth factor receptor (EGFR) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.
Methods:
Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.
Results:
EGFR protein overexpression (EGFRhigh) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFRhigh tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow tumours. Conversely, in EGFRhigh tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFRhigh (n=3) and mutated/EGFRlow tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.
Conclusions:
Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.
Insights
Epidermal growth factor receptor (EGFR) overexpression in prostate cancer (PC) correlates with increased relapse risk. EGFR mutation status and expression may guide targeted therapies for PC patients, warranting further investigation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating mutations in the epidermal growth factor receptor (EGFR) are known to sensitize tumors to tyrosine kinase inhibitors (TKIs).
- Prostate cancer (PC) is a significant health concern, and exploring novel therapeutic targets is crucial for improving patient outcomes.
- EGFR's role in PC progression and its potential as a therapeutic target remain areas of active investigation.
Purpose of the Study:
- To analyze EGFR expression, mutation status, and gene expression profiles in prostate cancer (PC) tissues.
- To investigate the potential of EGFR-targeted therapies in PC by establishing a rationale based on molecular findings.
- To correlate EGFR status with clinical outcomes, specifically biochemical relapse risk.
Main Methods:
- Tumor tissues from 100 radical prostatectomy PC patients were analyzed for EGFR mutations in the TK domain (exons 18-21) and EGFR protein expression via immunohistochemistry.
- Gene expression profiling was performed on 51 PC samples using oligo-microarrays.
- Statistical analyses, including hazard ratio calculations, were used to assess the relationship between EGFR status and biochemical relapse.
Main Results:
- EGFR protein overexpression (EGFRhigh) was observed in 36% of PC samples, and mutations were present in 13%.
- Patients with EGFRhigh tumors showed a significantly increased risk of biochemical relapse (HR 2.52, p=0.02) compared to EGFRlow tumors.
- A 79-gene signature differentiating mutated from non-mutated EGFRhigh tumors was identified, with specific genes implicated in PC progression.
Conclusions:
- EGFR status (expression and mutation) may serve as a prognostic biomarker for stratifying PC patients.
- The findings suggest a potential role for EGFR-directed therapies in specific subsets of PC patients.
- Further validation in larger patient cohorts is recommended to confirm these results and their clinical implications.