Cell-free circulating plasma hTERT mRNA is a useful marker for prostate cancer diagnosis and is associated with poor prognosis tumor characteristics.

BACKGROUND: Serum prostate-specific antigen (PSA) is the most widely used marker for diagnosing prostate cancer (PCa). It lacks specificity and predictive value, resulting in inaccurate diagnoses and overtreatment of the disease. The aim of this study was to assess the usefulness of plasma telomerase reverse transcriptase (hTERT) mRNA as a diagnostic and prognostic tool for PCa and its association with clinicopathological parameters of tumors. PRINCIPAL FINDINGS: Plasma hTERT mRNA levels were determined by qRT-PCR in 105 consecutive patients with elevated PSA levels and in 68 healthy volunteers. The diagnostic accuracy, the efficacy as a prognostic factor of biochemical recurrence and the association with tumor clinicopathological parameters of plasma hTERT mRNA and serum PSA tests were determined using univariate and multivariate analyses. The results show that plasma hTERT mRNA is a non-invasive biomarker for PCa diagnosis that shows higher sensitivity (85% vs. 83%), specificity (90% vs. 47%), positive predictive value (83% vs. 56%), and negative predictive value (92% vs. 77%) than serum PSA. Plasma hTERT mRNA is significantly associated with poor prognosis tumor clinicopathological parameters and is a significant independent predictor of PCa (p<0.0001). Univariate analysis identified plasma hTERT mRNA (but not serum PSA) as a significant prognostic factor of biochemical recurrence. Plasma hTERT mRNA Kaplan-Meier curves confirmed the significant differences between groups and patients with higher levels than the cut-off value showed diminished recurrence-free survival (p=0.004), whereas no differences were observed with serum PSA (p=0.38). Multivariate analysis indicated that plasma hTERT mRNA (but not serum PSA) and stage were significantly associated with biochemical recurrence. CONCLUSIONS: Overall, these findings indicate that hTERT mRNA is a useful non-invasive tumor marker for the molecular diagnosis of PCa, affording a greater diagnostic and prognostic accuracy than the PSA assay and may be of relevance in the follow-up of the disease.

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

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.