Biomedical subjects

Tracy Downs

Publications and source records attributed to Tracy Downs.

3 recordsLinked to original sources

PubMed2006

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.

Aged↗

PubMed2006

Profiling alternatively spliced mRNA isoforms for prostate cancer classification.

BACKGROUND: Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. RESULTS: As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. CONCLUSION: These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays.

Algorithms↗

PubMed2002

Is ethnicity an independent predictor of prostate cancer recurrence after radical prostatectomy?

PURPOSE: Prostate cancer incidence and mortality are higher in black than in white American men. We determined whether ethnicity is an independent predictor of disease recurrence in men undergoing radical prostatectomy. MATERIALS AND METHODS: We studied 1,468 patients who underwent radical prostatectomy at the University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor database, a longitudinal disease registry of patients with prostate cancer. Preoperative characteristics, including age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage, biopsy Gleason score and percent positive prostate biopsies at diagnosis were determined in each patient. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment at least 6 months after surgery. Cox proportional hazards analysis was performed to determine independent predictors of time to disease recurrence. To control for pretreatment disease characteristics simultaneously patients were assigned to previously described risk groups based on clinical tumor stage, PSA at diagnosis and biopsy Gleason score. The likelihood of disease recurrence per risk group stratified according to ethnicity was determined using the Kaplan-Meier method and compared using the log rank test. Additional multivariate analysis was performed in the subset of patients enrolled in Cancer of the Prostate Strategic Urological Research Endeavor on whom education and income information was available. RESULTS: Disease recurred in 304 of the 1,468 patients (21%). Black ethnicity, serum PSA at diagnosis, biopsy Gleason score and percent positive prostate biopsies were independent predictors of recurrence on multivariate analysis. Black ethnicity remained an independent predictor of disease recurrence in the multivariate model after stratifying patients into risk groups (p = 0.0007). Ethnicity was most important in patients at high risk, in whom estimated 5-year disease-free survival was 65% and 28% in white and black men, respectively. Education, income and ethnicity correlated highly. When education and income were entered into the multivariate model, ethnicity was no longer an independent predictor of outcome after prostatectomy. CONCLUSIONS: Ethnicity appears to be an independent predictor of disease recurrence after adjusting for pretreatment measures of disease extent in patients undergoing radical prostatectomy. It appears to be particularly important in those with high risk disease characteristics. However, black ethnicity, education and income are highly correlated variables, suggesting that sociodemographic factors may contribute to the poorer outcomes in black patients even after adjusting for differences in pretreatment disease characteristics.

Black or African American↗