Abstract
Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities. To investigate age-specific tumor associated gene signatures and their potential biomarkers for disease aggressiveness, this study was designed and stratified into well and poorly differentiated tumor types of young (42–58 years) and old (66–73 years) prostate cancer patients. The differentially expressed genes related to tumor-normal differences between non-familial prostate cancer patients were identified and several genes uniquely associated with the age and tumor differentiation are markedly polarized. Overexpressed genes known to be associated with somatic genomic alterations was predominantly found in young men, such as TMPRESS2-ERG and c-MYC. On the other hand, old men have mostly down-regulated gene expressions indicating the loss of protective genes and reduced cell mediated immunity indicated by decreased HLA-A and HLA-B expression. The normalization for the benign signatures between the age groups indicates a significant age and tumor dependent heterogeneity exists among the patients with a great potential for age-specific and tumor differentiation-based therapeutic stratification of prostate cancer.
Highlights
Prostate cancer is known as a disease of old men and age is the greatest risk factor for cancer development
We evaluated tumor samples from 40 Caucasian American (CA) prostate cancer patients who underwent radical prostatectomy from a common and homogenous tumor subtype, and recurrent prostate-specific antigen (PSA) from 40 Caucasian American (CA) prostate cancer patients
We found that most of the unique genes expressed in young patients are upregulated in in all the tumor types and recurring PSA (rPSA) group, whereas in old patients all the uniquely expressed genes were predominantly down regulated, suggesting the fundamental tumor development biology differences associated with patient age
Summary
Prostate cancer is known as a disease of old men and age is the greatest risk factor for cancer development. The prostate cancer associated mortality among young men with high grade tumor is much higher as compared to old men (4, 5). It was noted that men who develop prostate cancer before 50 years of age, are more likely to have a family history of prostate cancer These men were found to have worse clinicopathologic features, higher incidence of biochemical recurrence after radical prostatectomy, and lower survival probability (4, 7). Men who develop prostate cancer after 70 years of age had better clinicopathologic features, lower incidence of biochemical recurrence, and greater overall survival (8). These findings suggest a clinically relevant age-associated difference among men with prostate cancer
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