Abstract
To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.
Highlights
Prostate specific antigen (PSA) has emerged as a useful tumor marker in oncology and PSAbased screening is widely used despite a relative lack of both specificity, leading to overdiagnosis and treatment of early stage prostate cancer, and sensitivity, leading to prostate cancer not being detected early enough [1,2,3,4,5]
Current clinical biomarkers for prostate cancer lack specificity and sensitivity to reliably distinguish aggressive versus non-aggressive prostate cancer [2,3,4,5]
Unlike other previously published tissue specific expression studies, we combined a state of the art RNA-seq data set describing the prostate specific transcriptome with corresponding in situ protein expression in benign prostate
Summary
Prostate specific antigen (PSA) has emerged as a useful tumor marker in oncology and PSAbased screening is widely used despite a relative lack of both specificity, leading to overdiagnosis and treatment of early stage prostate cancer, and sensitivity, leading to prostate cancer not being detected early enough [1,2,3,4,5]. There is a need for better markers for early detection of prostate cancer. Tissue architecture is abnormal which facilitates PSA leakage to capillaries in the stromal compartment. Non-malignant prostate conditions, including prostatitis and benign prostatic hyperplasia (BPH), can lead to elevated serum PSA, limiting the specificity of PSA elevation for cancer detection [7]. Determining which patients require further examination with transrectal ultrasonography (TRUS)-guided biopsies remains a significant problem
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