Prostate Cancer Gene Profiles (HJF 346-13)

Prostate cancer (PCa) has the highest heritability and widest racial disparities of any cancer. African Americans (AAs) in the United States are known to have a higher incidence and mortality for PCa compared to Caucasian Americans (CAs).

Researchers at the Henry M. Jackson Foundation (HJF), Uniformed Services University for Health Sciences (USU), and Genomatix Software have identified gene expression profiles associated with PCa that can differentiate between AA and CA subjects. Integrating identified genomic data with clinical and other multifactorial risk data for diagnosis, prognosis and treatment is believed to help reduce disparities and improve clinical outcomes.

Applications and Advantages

Unique Gene Profiles: PCa gene expression profiles unique to AAs have been identified
Accurate Diagnosis/Prognosis: Use of ethnic-specific markers provides more accurate diagnostic and/or prognostic potential
Patient Stratification:Measurement of gene expression at nucleic acid or protein level helps stratify patients based on ethnicity, severity, or aggressiveness of cancer
Diagnostic and Prognostic Kits: Potential for developing kits with probes for diagnosis and prognosis in AA and CA subjects

Innovation Description

PCa is the second leading cause of cancer-related death in men in the United States. AA men have the highest incidence and mortality from PCa compared with other races. Studies show that AA men have higher PSA at diagnosis, higher grade disease on biopsy, greater volume for each stage, shorter PSA doubling time before radical prostatectomy as well as different tumor microenvironment. Hence, it is critical to explore the role of different prostate carcinogenesis pathways to develop more robust diagnosis and treatment strategies.

Our researchers identified a set of seven genes in patients of African descent and a set of eight genes in CA patients for use in diagnosing or prognosing PCa patients (Fig. 1). Further, a plurality of fifteen gene profile expressions that indicate prostate cancer were identified in subjects irrespective of ethnicity.

Developing diagnostic kits with probes that can detect the ethnic-specific PCa biomarkers provide more accurate diagnostic and/or prognostic potential and offer more informed treatment options. Further, identified gene expression profiles can be used to screen therapeutic drugs in clinical trials or animal models for PCa studies.

Fig. 1 Heatmap showing genes that are consistently
over expressed in AA patients and simultaneously
under expressed or show no change in CA patients.

Inventors

Shiv K. Srivastava, Ph.D., USU
Albert L. Dobi, Ph.D., HJF
Gyorgy Petrovics, Ph.D., HJF
Thomas B. Werner, Ph.D., Genomatix Software, Inc.
Martin Seifert, Genomatix Software, Inc.
Matthias Scherf, Genomatix Software, Inc.

Innovation Status

Histologically defined and precisely dissected primary PCa specimens were used for the study. Next generation sequencing techniques were used to identify high quality genome sequence data. Hierarchical clustering analysis (HCA) was performed on tumor and normal samples.