Abstract
BackgroundSerum 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 FindingsPlasma 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.ConclusionsOverall, 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.
Highlights
Prostate cancer (PCa) is, with the exception of skin cancer, the most frequently diagnosed cancer among men in developed societies and the second cause of death from cancer after lung cancer [1]
Overall, these findings indicate that hTERT mRNA is a useful non-invasive tumor marker for the molecular diagnosis of prostate cancer (PCa), affording a greater diagnostic and prognostic accuracy than the prostate-specific antigen (PSA) assay and may be of relevance in the follow-up of the disease
Statistical Methods Plasma hTERT mRNA levels and serum PSA levels were compared with clinicopathological parameters using MannWhitney U and Kruskal-Wallis non-parametric tests, since a Kolmogorov-Smirnov test revealed that neither hTERT mRNA nor serum PSA was normally distributed
Summary
Prostate cancer (PCa) is, with the exception of skin cancer, the most frequently diagnosed cancer among men in developed societies and the second cause of death from cancer after lung cancer [1]. The use of serum PSA to screen for PCa is controversial and not unanimously recommended by the international medical community. This discrepancy is due to the fact that the PSA test has limited specificity and predictive value, resulting in a significant number of false positives and, unnecessary biopsies [3]. 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
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