2014
DOI: 10.1186/1477-5956-12-40
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Automated quantitative multiplex immunofluorescence in situ imaging identifies phospho-S6 and phospho-PRAS40 as predictive protein biomarkers for prostate cancer lethality

Abstract: BackgroundWe have witnessed significant progress in gene-based approaches to cancer prognostication, promising early intervention for high-risk patients and avoidance of overtreatment for low-risk patients. However, there has been less advancement in protein-based approaches, even though perturbed protein levels and post-translational modifications are more directly linked with phenotype. Most current, gene expression-based platforms require tissue lysis resulting in loss of structural and molecular informatio… Show more

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Cited by 58 publications
(48 citation statements)
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“…Of importance is that, we have used a multiplex proteomics imaging platform (23) for quantitative measurements of eight independent biomarkers in intact tissue to generate the risk score (Supplementary Appendix). This in situ approach has the advantage compared with other tests using homogenized tissue (19,32), as it requires relatively few cancer cells (which is common of the biopsy specimens) and is not sensitive to variations in the ratios of benign tissue relative to tumor tissue.…”
Section: Discussionmentioning
confidence: 99%
“…Of importance is that, we have used a multiplex proteomics imaging platform (23) for quantitative measurements of eight independent biomarkers in intact tissue to generate the risk score (Supplementary Appendix). This in situ approach has the advantage compared with other tests using homogenized tissue (19,32), as it requires relatively few cancer cells (which is common of the biopsy specimens) and is not sensitive to variations in the ratios of benign tissue relative to tumor tissue.…”
Section: Discussionmentioning
confidence: 99%
“…unbound to TORC1) inhibited FDCP1 apoptosis [40]. Similarly, p-PRAS40, along with SMAD4, CCND1, SPP1 and pS6, represent a recently developed novel 5-marker protein signature for predicting prostate cancerspecific death, thus suggesting that quantifying the phosphorylated states of these markers in intact tissue is a viable option [22].…”
Section: Pras40 In Prostate Cancermentioning
confidence: 98%
“…It has been reported that diabetic treatments correlate with increased cancer risk, but the literature linking the two pathologies is equivocal. Even though PRAS40 has been identified as a predictive protein biomarker for diverse cancers [22,23], its use as a dual prognostic marker in the pathophysiological prognosis of both cancer and diabetes remains to be elucidated. Such a dual biomarker would be quite valuable, as patients suffering from diabetes also have a higher risk of cancer [24,25].…”
Section: Role Of Pras40 In Diabetes and Other Metabolic Disordersmentioning
confidence: 99%
“…To do this, two tissue microarrays (TMAs) were derived from a series of prostatectomy specimens, one using the highest Gleason pattern observed in the specimen, and a second using the lowest. 76,77 Both TMAs were tested using a 12-protein panel that demonstrated similar ability to discriminate tumor aggressiveness (Gleason score ≥7, pT3b, N1, or M1) based on the AUC (using the highest Gleason pattern: AUC, 0.70; 95% CI, 0.62-0.77; using the lowest Gleason pattern: AUC, 0.72; 95% CI 0.64-0.79). 77 This initial panel was reduced to an eight-protein assay and validated for predicting unfavorable pathology (Gleason score ≥4+3 or non organ-confined disease) in a cohort of matched biopsy and prostatectomy specimens.…”
Section: Molecular Testing In Active Surveillancementioning
confidence: 99%