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Nanowire analysis of cancer-testis antigens as biomarkers of aggressive prostate cancer.

ABSTRACT: To demonstrate the ability of the nCounter Analysis System, a nanowire technology, to sensitively and accurately detect cancer-testis antigens (CTAs) in men with prostate cancer and correlate them with disease parameters. The clinical implementation of novel biomarkers is necessary to provide for individual disease treatment planning for men with prostate cancer. The CTAs, as cancer-associated biomarkers that may correlate with aggressive disease, have the potential to play an important role.Formalin-fixed, paraffin embedded samples were used from men undergoing radical prostatectomy for prostate cancer. The expression of CTAs along with control genes was measured from formalin-fixed, paraffin-embedded prostate cancer tissues using real-time polymerase chain reaction and the nCounter assay.Using a nanowire-based assay, ribonucleic acid (RNA) expression levels of the CTAs CSAG2 and NOL4 were found to be significantly higher in men with Gleason score (GS) 8-10 disease than those with GS ?4+3 disease. On the contrary, the RNA expression level of PAGE4 was lower in men with GS 8-10 disease than those with GS ?6 group. This study demonstrates that CTAs can be detected with a nanostring assay that is translatable and that a set of CTAs correlates with the clinical characteristics of the disease.CTAs represent unique, cancer-associated biomarkers with potential utility in the clinic. The nCounter nanowire technology provides an opportunity to evaluate this panel of CTAs associated with aggressive prostate cancer in a multi-institutional fashion.

SUBMITTER: Takahashi S

PROVIDER: S-EPMC4695987 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Nanowire analysis of cancer-testis antigens as biomarkers of aggressive prostate cancer.

Takahashi Sayuri S Shiraishi Takumi T Miles Nancy N Trock Bruce J BJ Kulkarni Prakash P Getzenberg Robert H RH

Urology 20150301 3

<h4>Objective</h4>To demonstrate the ability of the nCounter Analysis System, a nanowire technology, to sensitively and accurately detect cancer-testis antigens (CTAs) in men with prostate cancer and correlate them with disease parameters. The clinical implementation of novel biomarkers is necessary to provide for individual disease treatment planning for men with prostate cancer. The CTAs, as cancer-associated biomarkers that may correlate with aggressive disease, have the potential to play an ...[more]

PMID: 25733303

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Project description:PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ?8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ?8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

Dataset Information

Nanowire analysis of cancer-testis antigens as biomarkers of aggressive prostate cancer.

Publications

Nanowire analysis of cancer-testis antigens as biomarkers of aggressive prostate cancer.

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