Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec 27;12(12):e1006477.
doi: 10.1371/journal.pgen.1006477. eCollection 2016 Dec.

Gene Expression Differences in Prostate Cancers between Young and Old Men

Yuanchun Ding  1 , Huiqing Wu  2 , Charles Warden  3 , Linda Steele  1 , Xueli Liu  3 , M van Iterson  4 , Xiwei Wu  3 , Rebecca Nelson  2 , Zheng Liu  3 , Yate-Ching Yuan  3 , Susan L Neuhausen  1
Affiliations

Gene Expression Differences in Prostate Cancers between Young and Old Men

Yuanchun Ding et al. PLoS Genet. .

Abstract

Prostate cancer incidence is increasing in younger men. We investigated whether men diagnosed with Gleason 7 (3+4) T2 prostate cancer at younger ages (≤ 45 years, young cohort) had different mRNA and miRNA expression profiles than men diagnosed at older ages (71-74 years, older cohort). We identified differentially expressed genes (DEGs) related to tumor-normal differences between the cohorts. Subsequent pathway analysis of DEGs revealed that the young cohort had significantly more pronounced inflammatory and immune responses to tumor development compared to the older cohort. Further supporting a role of inflammation-induced immune-suppression in the development of early-onset prostate cancer, we observed significant up-regulation of CTLA4 and IDO1/TDO2 pathways in tumors of the young cohort. Moreover, over-expression of CTLA4 and IDO1 was significantly associated with biochemical recurrence. Our results provide clues on the mechanisms of tumor development and point to potential biomarkers for early detection and treatment for prostate cancer in young men.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Four main age:tissue interaction patterns for genes that have significant differences in tumor-induced gene expression by age.
Horizontal axis is tissue type and vertical axis is mean gene expression. For each interaction pattern, the trend of changes in expression from normal to tumor tissues for the older (dashed line) and young (solid line) cohorts were plotted. There was significantly increased expression in tumor tissue compared to corresponding normal tissue in the young cohort with insignificant change in expression in the older cohort (plot a), whereas in plot b, both cohorts showed increasing expression from normal to tumor with the larger change in the young cohort. In plot c, the young cohort had a significant decrease in expression in tumors compared to the normal tissue, with an insignificant change in the older cohort, whereas in plot d, there was a significant decrease in expression in the young cohort and a significant increase in the older cohort.
Fig 2
Fig 2. Boxplots and dotplots of four DEGs in the CTLA4 pathway.
All four DEGs demonstrate the type b age:tissue interaction pattern with significantly increased expression in tumor compared to normal samples in the young cohort and insignificant expression changes between tumor and normal samples in the older cohort. Patients with biochemical recurrence are shown with a pink color in the corresponding tumor samples.
Fig 3
Fig 3. Boxplots and dotplots of DASL data exhibiting outliers of expression in IDO1, TDO2, ALOX15 and DEFA6.
Patients with biochemical recurrence are shown with a pink color in the corresponding tumor samples.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Salinas CA, Tsodikov A, Ishak-Howard M, Cooney KA (2014) Prostate cancer in young men: an important clinical entity. Nat Rev Urol 11: 317–323. 10.1038/nrurol.2014.91 - DOI - PMC - PubMed
    1. Li J, German R, King J, Joseph D, Thompson T, et al. (2012) Recent trends in prostate cancer testing and incidence among men under age of 50. Cancer Epidemiol 36: 122–127. 10.1016/j.canep.2011.10.014 - DOI - PubMed
    1. Cetin K, Beebe-Dimmer JL, Fryzek JP, Markus R, Carducci MA (2010) Recent time trends in the epidemiology of stage IV prostate cancer in the United States: analysis of data from the Surveillance, Epidemiology, and End Results Program. Urology 75: 1396–1404. 10.1016/j.urology.2009.07.1360 - DOI - PMC - PubMed
    1. Lin DW, Porter M, Montgomery B (2009) Treatment and survival outcomes in young men diagnosed with prostate cancer: a Population-based Cohort Study. Cancer 115: 2863–2871. 10.1002/cncr.24324 - DOI - PMC - PubMed
    1. Merrill RM, Bird JS (2002) Effect of young age on prostate cancer survival: a population-based assessment (United States). Cancer Causes Control 13: 435–443. - PubMed