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. 2017 Jul 3;7:4538. doi: 10.1038/s41598-017-04731-4

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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CCND2 mRNA expression is strikingly downregulated in metastatic human prostate cancer and its underexpression correlates with disease aggressiveness. (a–g) CCND2 transcript levels are greatly decreased in primary and metastatic prostate tumor tissues in several clinical data sets^{30, 32–37}, including a cohort of prostate samples of Chinese men³². Normal, benign prostate gland. Primary, primary human prostate cancer. Metastasis, metastatic prostate samples. (h–j) Decreased CCND2 expression correlates with prostate tumor progression to high Gleason score in multiple cohorts of patients with prostate cancer^{28, 30, 38}. (k,l) CCND2 underexpression markedly correlates with elevated serum PSA levels in the Taylor et al.³⁰ and Nakagawa et al.²⁸ clinical data sets. PSA is a diagnostic marker of prostate gland malignancy. Pre.Treatment or Pre.Prostatectomy PSA refer to the PSA level prior to radical prostatectomy. In (a), CCND2 expression intensity was determined by RNA sequencing³²; (b–l), CCND2 expression intensity is log2 median-centered intensity as reported in Rhodes, D. R. et al.²⁶.