Two-dimensional transcriptome profiling: identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens.
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 approximately 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.
Li
Hai-Ri
HR
Department of Cellular and Molecular Medicine, San Diego Supercomputer Center, University of California, San Diego, La Jolla 92093-0651, USA.
Wang-Rodriguez
Jessica
J
Nair
T Murlidharan
TM
Yeakley
Joanne M
JM
Kwon
Young-Soo
YS
Bibikova
Marina
M
Zheng
Christina
C
Zhou
Lixin
L
Zhang
Kui
K
Downs
Tracy
T
Fu
Xiang-Dong
XD
Fan
Jian-Bing
JB
D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D012333:RNA, Messenger