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Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse
Jia, Zhenyu1; Rahmatpanah, Farah B.1; Chen, Xin1; Lernhardt, Waldemar2; Wang, Yipeng3; Xia, Xiao-Qin4; Sawyers, Anne1; Sutton, Manuel1; McClelland, Michael1,5; Mercola, Dan1; Jia, ZY (reprint author), Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92717 USA.
2012-08-01
Source PublicationPLOS ONE
ISSN1932-6203
Volume7Issue:8Pages:e41371
AbstractBiomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment) is less affected by genetic alteration and might therefore yield more consistent biomarkers in response to tumor aggressiveness. To this end we compared Affymetrix gene expression profiles in stroma near tumor and identified a set of 115 probe sets for which the expression levels were significantly correlated with time-to-relapse. We also compared patients that chemically relapsed shortly after prostatectomy (<1 year), and patients that did not relapse in the first four years after prostatectomy. We identified 131 differentially expressed microarray probe sets between these two categories. 19 probe sets (15 genes overlapped between the two gene lists with p<0.0001). We developed a PAM-based classifier by training on samples containing stroma near tumor: 9 rapid relapse patient samples and 9 indolent patient samples. We then tested the classifier on 47 different samples, containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for predicting outcomes for patients.; Biomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment) is less affected by genetic alteration and might therefore yield more consistent biomarkers in response to tumor aggressiveness. To this end we compared Affymetrix gene expression profiles in stroma near tumor and identified a set of 115 probe sets for which the expression levels were significantly correlated with time-to-relapse. We also compared patients that chemically relapsed shortly after prostatectomy (<1 year), and patients that did not relapse in the first four years after prostatectomy. We identified 131 differentially expressed microarray probe sets between these two categories. 19 probe sets (15 genes overlapped between the two gene lists with p<0.0001). We developed a PAM-based classifier by training on samples containing stroma near tumor: 9 rapid relapse patient samples and 9 indolent patient samples. We then tested the classifier on 47 different samples, containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for predicting outcomes for patients.
SubtypeArticle
KeywordGene-expression Tumor Microenvironment Radical Prostatectomy Active Surveillance Time Diagnosis Marker Cohort Cells Men
Department[Jia, Zhenyu; Rahmatpanah, Farah B.; Chen, Xin; Sawyers, Anne; Sutton, Manuel; McClelland, Michael; Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92717 USA; [Lernhardt, Waldemar] Proveri, San Diego, CA USA; [Wang, Yipeng] AltheaDx, San Diego, CA USA; [Xia, Xiao-Qin] Chinese Acad Sci, Dept Bioinformat, Inst Hydrobiol, Wuhan, Hubei, Peoples R China; [McClelland, Michael] Vaccine Res Inst San Diego, San Diego, CA USA
DOI10.1371/journal.pone.0041371
WOS HeadingsScience & Technology
Funding OrganizationNational Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054]
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000307212800017
WOS KeywordGENE-EXPRESSION ; TUMOR MICROENVIRONMENT ; RADICAL PROSTATECTOMY ; ACTIVE SURVEILLANCE ; TIME ; DIAGNOSIS ; MARKER ; COHORT ; CELLS ; MEN
Funding OrganizationNational Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054] ; National Institutes of Health Strategic Partners for the Evaluation of Cancer Signatures (SPECS) Consortium [U01 CA1148102]; National Cancer Institute Early Detection Research Network (EDRN) Consortium [U01 CA152738]; University of California of Irvine Faculty Career Development Award; Chao Family Comprehensive Cancer Center at University of California of Irvine; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-08-1-0720]; University of California of Irvine Institute for Cancer Research from the National Cancer Institute [T32CA009054]
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Cited Times:20[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/17270
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorJia, ZY (reprint author), Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92717 USA.
Affiliation1.Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92717 USA
2.Proveri, San Diego, CA USA
3.AltheaDx, San Diego, CA USA
4.Chinese Acad Sci, Dept Bioinformat, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
5.Vaccine Res Inst San Diego, San Diego, CA USA
Recommended Citation
GB/T 7714
Jia, Zhenyu,Rahmatpanah, Farah B.,Chen, Xin,et al. Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse[J]. PLOS ONE,2012,7(8):e41371.
APA Jia, Zhenyu.,Rahmatpanah, Farah B..,Chen, Xin.,Lernhardt, Waldemar.,Wang, Yipeng.,...&Jia, ZY .(2012).Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse.PLOS ONE,7(8),e41371.
MLA Jia, Zhenyu,et al."Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse".PLOS ONE 7.8(2012):e41371.
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