Two-dimensional transcriptome profiling: Identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens

Hai Ri Li, Jessica Wang-Rodriguez, T. Murlidharan Nair, Joanne M. Yeakley, Young Soo Kwon, Marina Bibikova, Christina Zheng, Lixin Zhou, Kui Zhang, Tracy Downs, Xiang Dong Fu, Jian Bing Fan

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

The expression of specific mRNA isoforms may uniquely reflect the biological state of a cell because it reflects the integrated outcome of both transcriptional and posttranscriptional regulation. In this study, we constructed a splicing array to examine ∼1,500 mRNA isoforms from a panel of genes previously implicated in prostate cancer and identified a large number of cell type-specific mRNA isoforms. We also developed a novel "two-dimensional" profiling strategy to simultaneously quantify changes in splicing and transcript abundance; the results revealed extensive covariation between transcription and splicing in prostate cancer cells. Taking advantage of the ability of our technology to analyze RNA from formalin-fixed, paraffin-embedded tissues, we derived a specific set of mRNA isoform biomarkers for prostate cancer using independent panels of tissue samples for feature selection and cross-analysis. A number of cancer-specific splicing switch events were further validated by laser capture microdissection. Quantitative changes in transcription/RNA stability and qualitative differences in splicing ratio may thus be combined to characterize tumorigenic programs and signature mRNA isoforms may serve as unique biomarkers for tumor diagnosis and prognosis.

Original languageEnglish (US)
Pages (from-to)4079-4088
Number of pages10
JournalCancer Research
Volume66
Issue number8
DOIs
StatePublished - Apr 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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