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Expression of IGF/insulin receptor in prostate cancer tissue and progression to lethal disease
- Source :
- Carcinogenesis. 39(12)
- Publication Year :
- 2018
-
Abstract
- Circulating insulin-like growth factor-1 (IGF-1) is consistently associated with prostate cancer risk. IGF-1 binds to IGF-1 receptor (IGF1R) and insulin receptor (IR), activating cancer hallmark pathways. Experimental evidence suggests that TMPRSS2:ERG may interact with IGF/insulin signaling to influence progression. We investigated IGF1R and IR expression and its association with lethal prostate cancer among 769 men. Protein expression of IGF1R, IR and ERG (i.e. a surrogate of ERG fusion genes) were assayed by immunohistochemistry. Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for clinical characteristics. Among patients, 29% had strong tumor IGF1R expression and 10% had strong IR expression. During a mean follow-up of 13.2 years through 2012, 80 men (11%) developed lethal disease. Tumors with strong IGF1R or IR expression showed increased cell proliferation, decreased apoptosis and a higher prevalence of ERG. In multivariable models, strong IGF1R was associated with a borderline increased risk of lethal prostate cancer (HR 1.7; 95% CI 0.9-3.1). The association appeared greater in ERG-positive tumors (HR 2.8; 95% CI 0.9-8.4) than in ERG-negative tumors (HR 1.3; 95% CI 0.6-3.0, p-heterogeneity 0.08). There was no association between IR and lethal prostate cancer (HR 0.8; 95% CI 0.4-1.9). These results suggest that tumor IGF1R expression may play a role in prostate cancer progression to a lethal phenotype and that ERG-positive tumors may be more sensitive to IGF signaling. These data may improve our understanding of IGF signaling in prostate cancer and suggest therapeutic options for disease subtypes.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Oncogene Proteins, Fusion
Apoptosis
TMPRSS2
Receptor, IGF Type 1
Fusion gene
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Transcriptional Regulator ERG
medicine
Biomarkers, Tumor
Humans
Insulin
Insulin-Like Growth Factor I
Cancer Biomarkers and Molecular Epidemiology
Insulin-like growth factor 1 receptor
Aged
Cell Proliferation
biology
business.industry
Cancer
Prostatic Neoplasms
Receptors, Somatomedin
General Medicine
medicine.disease
Receptor, Insulin
Gene Expression Regulation, Neoplastic
Insulin receptor
030104 developmental biology
030220 oncology & carcinogenesis
immunohistochemistry
biology.protein
Cancer research
IGF-1
Disease Progression
Immunohistochemistry
business
Erg
Signal Transduction
Subjects
Details
- ISSN :
- 14602180
- Volume :
- 39
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....d0d814e187008673843eafd01f1046fa