University of Oulu

Chen, Y., Zhang, Q., Wang, Q., Li, J., Sipeky, C., Xia, J., Gao, P., Hu, Y., Zhang, H., Yang, X., Chen, H., Jiang, Y., Yang, Y., Yao, Z., Chen, Y., Gao, Y., Tan, A., Liao, M., Schleutker, J., Xu, J., Sun, Y., Wei, G., Mo, Z. (2017) Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression. Scientific Reports, 7 (1), . doi:10.1038/s41598-017-04731-4

Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression

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Author: Chen, Yang1,2,3; Zhang, Qin4,5; Wang, Qiuyan1,3;
Organizations: 1Center for Genomic and Personalized Medicine, Guangxi Medical University
2Department of Urology and Nephrology, the First Affiliated Hospital of Guangxi Medical University
3Guangxi key laboratory for genomic and personalized medicine, Guangxi collaborative innovation center for genomic and personalized medicine
4Biocenter Oulu, University of Oulu
5Faculty of Biochemistry and Molecular Medicine, University of Oulu
6The Guangxi Zhuang Autonomous Region Family Planning Research Center
7Department of Medical Biochemistry and Genetics, University of Turku
8Medical Research Center, Guangxi Medical University
9Program for Personalized Cancer Care, NorthShore University HealthSystem
10Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital
11Fudan Institute of Urology, Huashan Hospital, Fudan University
12Department of Urology, Shanghai Changhai Hospital, The Second Military Medical University
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201708238191
Language: English
Published: Springer Nature, 2017
Publish Date: 2017-08-23
Description:

Abstract

The RTK/ERK signaling pathway has been implicated in prostate cancer progression. However, the genetic relevance of this pathway to aggressive prostate cancer at the SNP level remains undefined. Here we performed a SNP and gene-based association analysis of the RTK/ERK pathway with aggressive prostate cancer in a cohort comprising 956 aggressive and 347 non-aggressive cases. We identified several loci including rs3217869/CCND2 within the pathway shown to be significantly associated with aggressive prostate cancer. Our functional analysis revealed a statistically significant relationship between rs3217869 risk genotype and decreased CCND2 expression levels in a collection of 119 prostate cancer patient samples. Reduced expression of CCND2 promoted cell proliferation and its overexpression inhibited cell growth of prostate cancer. Strikingly, CCND2 downregulation was consistently observed in the advanced prostate cancer in 18 available clinical data sets with a total amount of 1,095 prostate samples. Furthermore, the lower expression levels of CCND2 markedly correlated with prostate tumor progression to high Gleason score and elevated PSA levels, and served as an independent predictor of biochemical relapse and overall survival in a large cohort of prostate cancer patients. Together, we have identified an association of genetic variants and genes in the RTK/ERK pathway with prostate cancer aggressiveness, and highlighted the potential importance of CCND2 in prostate cancer susceptibility and tumor progression to metastasis.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Issue: 7
Article number: 4538
DOI: 10.1038/s41598-017-04731-4
OADOI: https://oadoi.org/10.1038/s41598-017-04731-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
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