Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of the RNA-Seq data of castration resistant prostate cancer (CRPCa)

ABSTRACT: Prostate cancer is the second leading cancer that causes the death of American men. In this study, we perform an integrative analysis of the whole-transcriptome of metastatic prostate cancer clinical samples. Specifically, we prepare our samples using an innovative protocol NuGEN, which captures the profile of the total RNA, rather than only the mRNA as the popular polyA selection protocol does. Unexpectedly high intronic expressions are observed including the gene AR (Androgen Receptor) and KLK3/PSA, a marker of prostate cancer. Further, certain amount of reads can be found to be across the intron-exon boundaries, suggesting that they come from unspliced pre-mRNAs. Interestingly, we also observe high splicing on a non-coding RNA MALAT-1. We believe that the aberrant splicing patterns are associated with prostate cancer development. Analysis of 8 clinical samples of metastatic prostate cancer patients

ORGANISM(S): Homo sapiens

SUBMITTER: hao zhao

PROVIDER: E-GEOD-31528 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer.

Sowalsky Adam G AG Xia Zheng Z Wang Liguo L Zhao Hao H Chen Shaoyong S Bubley Glenn J GJ Balk Steven P SP Li Wei W

Molecular cancer research : MCR 20140904 1

<h4>Unlabelled</h4>Men with metastatic prostate cancer who are treated with androgen deprivation therapies (ADT) usually relapse within 2 to 3 years with disease that is termed castration-resistant prostate cancer (CRPC). To identify the mechanism that drives these advanced tumors, paired-end RNA-sequencing (RNA-seq) was performed on a panel of CRPC bone marrow biopsy specimens. From this genome-wide approach, mutations were found in a series of genes with prostate cancer relevance, including AR ...[more]

PMID: 25189356

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Project description:Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging, hence sampling circulating tumor cells (CTCs) may reveal drug resistance mechanisms. We established single cell RNA-sequencing profiles of 77 intact CTCs isolated from 13 patients (mean 6 CTCs/patient) using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing on AR inhibitor, compared with untreated cases indicates activation of noncanonical Wnt signaling (P=0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, while its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure. A total of 221 single candidate prostate CTCs were isolated from 18 patients with metastatic prostate cancer and 4 patients with localized prostate cancer. Of these, 133 cells (60%) had RNA of sufficient quality for amplification and next generation RNA sequencing, and 122 (55%) had >100,000 uniquely aligned sequencing reads. In addition to candidate CTCs, we also obtained comprehensive transcriptomes for 12 bulk primary prostate cancers (macrodissected for >70% tumor content), 30 single cells derived from four different prostate cancer cell lines, and 5 patient-derived leukocyte controls. The leukocytes were readily distinguished by their expression of hematopoietic lineage markers and served to exclude any CTCs with potentially contaminating signals. Strict expression thresholds were used to define lineage-confirmed CTCs, scored by prostate lineage-specific genes (PSA, PSMA, AMACR, AR) and standard epithelial markers (KRT7, KRT8, KRT18, KRT19, EpCAM). 28 cells were excluded given the presence of leukocyte transcripts suggestive of cellular contamination or misidentification during selection, and 17 cells were excluded given low expression of both prostate lineage-specific genes and 5 standard epithelial markers. The remaining 77 cells, defined as lineage-confirmed CTCs, displayed expression of either prostate lineage-specific or epithelial genes, and low expression of leukocyte-specific genes, consistent with their tumor of origin.

Dataset Information

Analysis of the RNA-Seq data of castration resistant prostate cancer (CRPCa)

Publications

Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer.

Similar Datasets

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