Biomolecular markers of outcome prediction in prostate cancer

Lopergolo, Alessia; Zaffaroni, Nadia

doi:10.1002/cncr.24346

Cited by 29 publications

(19 citation statements)

References 48 publications

(52 reference statements)

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“…Research over the past decade has identified a number of biomarkers that are associated with high Gleason grade disease [7]–[13]. Previous studies from our laboratory found a correlation between expression of FLICE-inhibitory protein (FLIP) and tumor grade in human prostate cancer [13].…”

Section: Introductionmentioning

confidence: 93%

Predictive Value of Sp1/Sp3/FLIP Signature for Prostate Cancer Recurrence

et al. 2012

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Prediction of prostate cancer prognosis is challenging and predictive biomarkers of recurrence remain elusive. Although prostate specific antigen (PSA) has high sensitivity (90%) at a PSA level of 4.0 ng/mL, its low specificity leads to many false positive results and considerable overtreatment of patients and its performance at lower ranges is poor. Given the histopathological and molecular heterogeneity of prostate cancer, we propose that a panel of markers will be a better tool than a single marker. We tested a panel of markers composed of the anti-apoptotic protein FLIP and its transcriptional regulators Sp1 and Sp3 using prostate tissues from 64 patients with recurrent and non-recurrent cancer who underwent radical prostatectomy as primary treatment for prostate cancer and were followed with PSA measurements for at least 5 years. Immunohistochemical staining for Sp1, Sp3, and FLIP was performed on these tissues and scored based on the proportion and intensity of staining. The predictive value of the FLIP/Sp1/Sp3 signature for clinical outcome (recurrence vs. non-recurrence) was explored with logistic regression, and combinations of FLIP/Sp1/Sp3 and Gleason score were analyzed with a stepwise (backward and forward) logistic model. The discrimination of the markers was identified by sensitivity-specificity analysis and the diagnostic value of FLIP/Sp1/Sp3 was determined using area under the curve (AUC) for receiver operator characteristic curves. The AUCs for FLIP, Sp1, Sp3, and Gleason score for predicting PSA failure and non-failure were 0.71, 0.66, 0.68, and 0.76, respectively. However, this increased to 0.93 when combined. Thus, the “biomarker signature” of FLIP/Sp1/Sp3 combined with Gleason score predicted disease recurrence and stratified patients who are likely to benefit from more aggressive treatment.

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Section: Introductionmentioning

confidence: 93%

Predictive Value of Sp1/Sp3/FLIP Signature for Prostate Cancer Recurrence

et al. 2012

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“…Current diagnostic methods; measuring levels of prostate specific antigen (PSA) in blood samples and examining needle biopsies from the prostate under light microscopy, are however not particularly effective in separating cases of aggressive PCa from the even more prevalent and indolent forms of PCa that often can be left without treatment, or in separating cancer from other non-malignant prostate disorders [1], [2]. Using a variety of techniques multiple investigators have therefore tried to find novel diagnostic methods and prognostic markers that can separate aggressive from more indolent forms of PCa (reviewed in [3]). …”

Section: Introductionmentioning

confidence: 99%

Metabolomic Characterization of Human Prostate Cancer Bone Metastases Reveals Increased Levels of Cholesterol

et al. 2010

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BackgroundMetastasis to the bone is one clinically important features of prostate cancer (PCa). Current diagnostic methods cannot predict metastatic PCa at a curable stage of the disease. Identification of metabolic pathways involved in the growth of bone metastases therefore has the potential to improve PCa prognostication as well as therapy.Methodology/Principal FindingsMetabolomics was applied for the study of PCa bone metastases (n = 20) in comparison with corresponding normal bone (n = 14), and furthermore of malignant (n = 13) and benign (n = 17) prostate tissue and corresponding plasma samples obtained from patients with (n = 15) and without (n = 13) diagnosed metastases and from men with benign prostate disease (n = 30). This was done using gas chromatography-mass spectrometry for sample characterization, and chemometric bioinformatics for data analysis. Results were verified in a separate test set including metastatic and normal bone tissue from patients with other cancers (n = 7). Significant differences were found between PCa bone metastases, bone metastases of other cancers, and normal bone. Furthermore, we identified metabolites in primary tumor tissue and in plasma which were significantly associated with metastatic disease. Among the metabolites in PCa bone metastases especially cholesterol was noted. In a test set the mean cholesterol level in PCa bone metastases was 127.30 mg/g as compared to 81.06 and 35.85 mg/g in bone metastases of different origin and normal bone, respectively (P = 0.0002 and 0.001). Immunohistochemical staining of PCa bone metastases showed intense staining of the low density lipoprotein receptor and variable levels of the scavenger receptor class B type 1 and 3-hydroxy-3-methylglutaryl-coenzyme reductase in tumor epithelial cells, indicating possibilities for influx and de novo synthesis of cholesterol.Conclusions/SignificanceWe have identified metabolites associated with PCa metastasis and specifically identified high levels of cholesterol in PCa bone metastases. Based on our findings and the previous literature, this makes cholesterol a possible therapeutic target for advanced PCa.

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“…DNA, RNA, and protein markers all hold potential for innovations in prostate cancer screening. The applications of these markers to prostate cancer screening have been extensively reviewed in many studies (Li-Wan-Po et al, 2010;Lopergolo & Zaffaroni, 2009;Martin, Mucci, Loda, & Depinho, 2011;Ploussard & de la Taille, 2010;Urquidi, Rosser, & Goodison, 2012;Witte, 2009). Of these potential tests, only the Prostate Cancer Gene 3 (PCA3) test is commercially available.…”

Section: Development Of Genetic Testing For Prostate Cancermentioning

confidence: 99%