Plasma Glutamine as a Prognostic Biomarker in Localized Prostate Cancer: Comparison of Conventional Variables in Risk Stratification.

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From: Oncology(Vol. 35, Issue 9)
Publisher: Intellisphere, LLC
Document Type: Article
Length: 3,608 words
Lexile Measure: 1820L

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Abstract :

BACKGROUND: Glutamine uptake has been shown to contribute to local prostate cancer growth and therapeutic resistance. We investigated the biomarker potential of glutamine among known prognostic variables in localized prostate cancer. METHODS: Plasma glutamine was measured by bioluminescence assay (Promega) in clinically annotated, pre-radical prostatectomy (RP) samples granted by the Prostate Cancer Biorepository Network. Univariate and multivariable Cox regressions of biochemical recurrence-free survival (bRFS) were performed. The performance of multivariable models was assessed with Harrell's c-statistics with internal validation by estimating and correcting possible optimism in c-statistics using the bootstrap method with 1000 replicates. RESULTS: Plasma glutamine levels were measured in a total of 125 patients with localized prostate cancer prior to RP. The majority were Gleason score 7 (70%), pathologic T2c (59%), and N0 (95%). The median plasma glutamine level was 442 [micro]mol/L (interquartile range [IQR], 387-533) and median pre-RP prostate-specific antigen (PSA) was 5.36 (IQR, 4.4-7.5). The median bRFS was 6.19 years (95% CI, 3.96-6.82) with a 5-year bRFS rate of 55% (95% CI, 46%-63%). On univariate analysis, glutamine level was not significantly associated with known prognostic variables or bRFS (HR, 0.98; 95% CI, 0.83-1.15; P = .80), although higher pre-RP PSA and Gleason score, perforated capsule, positive margins, N1 disease, higher pathologic T stage, and higher D'Amico and Cambridge Prognostic Group (CPG) risk scores were significantly associated with bRFS (all P CONCLUSIONS: Pre-RP glutamine levels are not predictive of prognosis in localized prostate cancer. Risk scores such as D'Amico or CPG remain the top predictors of bRFS in our cohort. Further development of novel prognostic biomarkers--eg, genomic classifiers--is needed to better risk stratify indolent from biologically aggressive prostate cancer.

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Gale Document Number: GALE|A679525834