Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

Abstract

The goal of this project was to develop molecular models to distinguish significant (Gleason score 7 and higher) prostate cancer (PCa) from indolent (Gleason score 6) PCa using biomarkers in the benign (non-neoplastic) prostate tissue and in high grade PIN (HGPIN) samples. Aim1 focused in gene expression and methylation analyses by sequencing in a large set of samples to identify gene expression and epigenetic candidate biomarkers. Most promising gene expression biomarkers which were validated in multiple independent sets were selected to develop two logistic regression models. The model for testing in the bulk tissue incorporated 6 genes, including NAV1, LYST, ADD3, SMC5, CEP350, and KIAA2026. This model was validated in 4 of the 5 datasets we tested. Another model to distinguish HGPIN samples in indolent and significant cases was based on three genes including LRRC4C, SUGT1, and KLHL28 and was validated in an independent dataset. This career development grant was an excellent opportunity for us to study prostate cancer field and to realize the clinical potential of cancer field effect. We were able to obtain a sizable set of data which will be used in future research in projects aimed at prevention of PCa and also early detection of significant PCa.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2016
Accession Number
AD1028422

Entities

People

  • Farhad F. Kosari
  • G. Vasmatzis
  • J. C. Cheville
  • M. Manemann
  • R. J. Karnes
  • S. J. Murphy

Tags

DTIC Thesaurus Topics

  • Biological Markers
  • Biomedical Research
  • Contracts
  • Data Sets
  • Department Of Defense
  • Electronic Mail
  • Gene Expression
  • Information Operations
  • Methylation
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Rna Sequence Analysis
  • Tissues
  • Validation

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Oncology
  • Oncology (Cancer Research).