Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression
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 aggressi...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/aac9b6a6df4847cca58d920e01269218 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:aac9b6a6df4847cca58d920e01269218 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:aac9b6a6df4847cca58d920e012692182021-12-02T15:06:25ZGenetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression10.1038/s41598-017-04731-42045-2322https://doaj.org/article/aac9b6a6df4847cca58d920e012692182017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04731-4https://doaj.org/toc/2045-2322Abstract 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.Yang ChenQin ZhangQiuyan WangJie LiCsilla SipekyJihan XiaPing GaoYanling HuHaiying ZhangXiaobo YangHaitao ChenYonghua JiangYuehong YangZiting YaoYinchun ChenYong GaoAihua TanMing LiaoJohanna SchleutkerJianfeng XuYinghao SunGong-Hong WeiZengnan MoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Yang Chen Qin Zhang Qiuyan Wang Jie Li Csilla Sipeky Jihan Xia Ping Gao Yanling Hu Haiying Zhang Xiaobo Yang Haitao Chen Yonghua Jiang Yuehong Yang Ziting Yao Yinchun Chen Yong Gao Aihua Tan Ming Liao Johanna Schleutker Jianfeng Xu Yinghao Sun Gong-Hong Wei Zengnan Mo Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| 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. |
| format |
article |
| author |
Yang Chen Qin Zhang Qiuyan Wang Jie Li Csilla Sipeky Jihan Xia Ping Gao Yanling Hu Haiying Zhang Xiaobo Yang Haitao Chen Yonghua Jiang Yuehong Yang Ziting Yao Yinchun Chen Yong Gao Aihua Tan Ming Liao Johanna Schleutker Jianfeng Xu Yinghao Sun Gong-Hong Wei Zengnan Mo |
| author_facet |
Yang Chen Qin Zhang Qiuyan Wang Jie Li Csilla Sipeky Jihan Xia Ping Gao Yanling Hu Haiying Zhang Xiaobo Yang Haitao Chen Yonghua Jiang Yuehong Yang Ziting Yao Yinchun Chen Yong Gao Aihua Tan Ming Liao Johanna Schleutker Jianfeng Xu Yinghao Sun Gong-Hong Wei Zengnan Mo |
| author_sort |
Yang Chen |
| title |
Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| title_short |
Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| title_full |
Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| title_fullStr |
Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| title_full_unstemmed |
Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression |
| title_sort |
genetic association analysis of the rtk/erk pathway with aggressive prostate cancer highlights the potential role of ccnd2 in disease progression |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/aac9b6a6df4847cca58d920e01269218 |
| work_keys_str_mv |
AT yangchen geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT qinzhang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT qiuyanwang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT jieli geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT csillasipeky geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT jihanxia geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT pinggao geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yanlinghu geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT haiyingzhang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT xiaoboyang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT haitaochen geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yonghuajiang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yuehongyang geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT zitingyao geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yinchunchen geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yonggao geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT aihuatan geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT mingliao geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT johannaschleutker geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT jianfengxu geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT yinghaosun geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT gonghongwei geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression AT zengnanmo geneticassociationanalysisofthertkerkpathwaywithaggressiveprostatecancerhighlightsthepotentialroleofccnd2indiseaseprogression |
| _version_ |
1718388472428888064 |