Plasma hTERT mRNA discriminates between clinically localized and locally advanced disease and is a predictor of recurrence in prostate cancer patients

Abstract

Introduction: Since the introduction of prostate-specific antigen (PSA) testing, new prostate cancer (PCa) patients are diagnosed earlier and most have localized and locally advanced disease. Current diagnosis methods lack specificity and sensitivity, leading to overdiagnosis and overtreatment of patients with low-risk organ-confined localized disease. Therefore, new non-invasive molecular tools are needed to discriminate between localized and locally advanced disease.

Methods: Plasma telomerase reverse transcriptase (hTERT) mRNA levels were determined by qRT-PCR in 49 patients with localized and locally advanced PCa. Diagnostic accuracy and efficacy as a prognostic factor of biochemical recurrence of plasma hTERT mRNA were determined using univariate and multivariate analyses and compared with conventional tumor markers.

Results: Patients with locally advanced disease had significantly (p < 0.05) higher plasma hTERT mRNA and serum PSA levels than those with localized disease. Plasma hTERT mRNA test showed lower sensitivity (83% vs. 100%), higher specificity (73% vs. 43%), AUC ROC curve (0.911 vs. 0.757), and positive likelihood ratios (6.17 vs. 1.76) than the PSA assay in discriminating between localized and locally advanced disease. At multivariate analysis, plasma hTERT mRNA levels and age but not PSA showed a positive trend (p = 0.05) in the risk of locally advanced PCa. On univariate analysis, plasma hTERT mRNA and serum PSA were identified as significant prognostic factors of biochemical recurrence. Using ROC curves and the appropriate cutoff, both tests showed high sensitivity (85%) and specificity (72%). Kaplan–Meier curves confirmed the significant differences between the groups and patients with higher levels than the cutoff value showed diminished recurrence-free survival (p < 0.05). At multivariate analysis, Gleason score and PSA were the strongest factors associated with biochemical recurrence (p < 0.05), whereas hTERT mRNA did not reach statistical significance, although a positive trend was observed (p = 0.09).

Conclusion: Plasma hTERT mRNA quantification can be both a useful non-invasive tumor marker for discriminating between localized and locally advanced PCa, as well as a prognostic factor of recurrence at the molecular level.

Keywords::

• circulating nucleic acids in plasma/serum
• CNAPS
• hTERT
• plasma
• prostate cancer
• telomerase

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