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Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer. 2013

Dogus Murat Altintas, and Nathalie Allioli, and Myriam Decaussin, and Simon de Bernard, and Alain Ruffion, and Jacques Samarut, and Virginie Vlaeminck-Guillem
Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon, CNRS UMR5242, INRA1288, Ecole Normale Supérieure de Lyon, Lyon, France.

BACKGROUND Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. METHODS ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). CONCLUSIONS By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). CONCLUSIONS We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.

UI MeSH Term Description Entries
D008297 Male Males
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000951 Antigens, Neoplasm Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin. Neoplasm Antigens,Tumor Antigen,Tumor Antigens,Antigen, Tumor,Antigens, Tumor
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012372 ROC Curve A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli. ROC Analysis,Receiver Operating Characteristic,Analysis, ROC,Analyses, ROC,Characteristic, Receiver Operating,Characteristics, Receiver Operating,Curve, ROC,Curves, ROC,ROC Analyses,ROC Curves,Receiver Operating Characteristics
D012669 Seminal Vesicles A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Seminal Vesicle,Vesicle, Seminal,Vesicles, Seminal

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