Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival.

Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival. Research Abstract Details 

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Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival. Abstract Text:

Joseph R Sterbis,Chunling Gao,Bungo Furusato,Yongmei Chen,Syed Shaheduzzaman,Lakshmi Ravindranath,David J Osborn,Inger L Rosner,Albert Dobi,David G McLeod,Isabell A Sesterhenn,Shiv Srivastava,Jennifer Cullen,Gyorgy Petrovics,

PURPOSE: Alterations of the androgen receptor (AR)-mediated signaling through numerous mechanisms are increasingly recognized in prostate cancer (CaP) progression. We hypothesized that the assessment of well-defined AR transcriptional targets (e.g., PSA/HK3 mRNA) in CaP tissues will provide in vivo readout of AR dysfunctions. Moreover, quantitative expression features of PSA/HK3 mRNA in prostate tumor cells may serve as a prognostic indicator of disease progression. EXPERIMENTAL DESIGN: Paired benign and malignant epithelial cells (242 specimens) were obtained from laser capture microdissection of frozen OCT-embedded tissue sections prepared from radical prostatectomy specimens of 121 patients. Quantitative expression of PSA/HK3 mRNA in the matched malignant and benign cells was analyzed by real-time reverse transcription-PCR. RESULTS: CaP cells express significantly lower PSA/HK3 mRNA levels than matched benign cells (P = 0.0133). Moreover, low PSA/HK3 mRNA expression in malignant cells was associated with increased risk of biochemical recurrence (P = 0.0217), as well as with time to recurrence (P = 0.0371), in patients with intermediate preoperative serum prostate-specific antigen levels (2-10 ng/mL). The expression of androgen-dependent genes in clinical samples correlates with each other in patients with higher expression of PSA/HK3 mRNA but not in patients with lower expression of PSA/HK3 mRNA reflecting AR pathway dysfunction. CONCLUSIONS: Our study has unraveled a novel prognostic utility of quantitative measurements of PSA/HK3 mRNA reflecting AR transcriptional activity in CaP cells, which is independent of serum prostate-specific antigen. It also has potential in stratifying subsets of patients exhibiting progressive disease associated with dampened AR transcriptional functions who may be targeted by tailored therapeutic strategies.

Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival. Publishing Authors By Initials

JR Sterbis,C Gao,B Furusato,Y Chen,S Shaheduzzaman,L Ravindranath,DJ Osborn,IL Rosner,A Dobi,DG McLeod,IA Sesterhenn,S Srivastava,J Cullen,G Petrovics,

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Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 14

Page Numbers: 758-63

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Feb

YEAR: 2008

Higher Expression of the Androgen-Regulated Gene PSA/HK3 mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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AFFILIATION: Authors' Affiliations: Urology Service, Department of Surgery, Walter Reed Army Medical Center.

Country: United States

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MEDLINETA: Clin Cancer Res

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