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BMC Cancer

, 14:244

Translational oncology

Abstract

BackgroundPrognostic multibiomarker signatures in prostate cancer PCa may improve patient management and provide a bridge for developing novel therapeutics and imaging methods. Our objective was to evaluate the association between expression of 33 candidate protein biomarkers and time to biochemical failure BF after prostatectomy.

MethodsPCa tissue microarrays were constructed representing 160 patients for whom clinicopathologic features and follow-up data after surgery were available. Immunohistochemistry for each of 33 proteins was quantified using automated digital pathology techniques. Relationships between clinicopathologic features, staining intensity, and time to BF were assessed. Predictive modeling using multiple imputed datasets was performed to identify the top biomarker candidates.

ResultsIn univariate analyses, lymph node positivity, surgical margin positivity, non-localized tumor, age at prostatectomy, and biomarkers CCND1, HMMR, IGF1, MKI67, SIAH2, and SMAD4 in malignant epithelium were significantly associated with time to BF. HMMR, IGF1, and SMAD4 remained significantly associated with BF after adjusting for clinicopathologic features while additional associations were observed for HOXC6 and MAP4K4 following adjustment. In multibiomarker predictive models, 3 proteins including HMMR, SIAH2, and SMAD4 were consistently represented among the top 2, 3, 4, and 5 most predictive biomarkers, and a signature comprised of these proteins best predicted BF at 3 and 5 years.

ConclusionsThis study provides rationale for investigation of HMMR, HOXC6, IGF1, MAP4K4, SIAH2, and SMAD4 as biomarkers of PCa aggressiveness in larger cohorts.

KeywordsProstate cancer Aggressiveness Biomarker Signature Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-244 contains supplementary material, which is available to authorized users.

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Author: Anthony E Rizzardi - Nikolaus K Rosener - Joseph S Koopmeiners - Rachel Isaksson Vogel - Gregory J Metzger - Colleen L 

Source: https://link.springer.com/







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