Dataset Information

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.

ABSTRACT: Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jointly in a single model. We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes. This is the first study to identify associations between multiple SNPs and multiple in trans gene expression differences in cancer stroma. Potentially, a combination of SNPs and associated expression differences in prostate stroma may increase the power of risk assessment for individuals, and for cancer progression.

SUBMITTER: Chen X

PROVIDER: S-EPMC4359337 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.

Chen Xin X McClelland Michael M Jia Zhenyu Z Rahmatpanah Farah B FB Sawyers Anne A Trent Jeffrey J Duggan David D Mercola Dan D

Oncotarget 20150101 3

Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jo ...[more]

PMID: 25638161

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Project description:Typical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies.To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors.Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

Dataset Information

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.

Publications

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma.

Similar Datasets

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