Cell-Free Circulating Plasma hTERT mRNA Is a Useful Marker for Prostate Cancer Diagnosis and Is Associated with Poor Prognosis Tumor Characteristics

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.

Utilization of paramagnetic microparticles for automated isolation of free circulating mRNA as a new tool in prostate cancer diagnostics

“…There are numerous reports describing the connection of extracellular mRNA in connection with cancer diagnostics. For instance, Koperski et al described detection of tumor‐related tyrosinase mRNA in melanoma patients , Fleischhacker et al referred similar findings with hnRNP‐B1 and HER2/neu‐specific mRNA from sera of patients with malignant lung tumor , and results of study of March‐Villalba et al indicate that hTERT mRNA is an effective molecular marker for the diagnosis of prostate cancer . Based on our results, although serum MT2A mRNA appears to be a prospective marker for the diagnosis of prostate cancer, further studies including higher number of patients are required to validate its diagnostic value.…”

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…Still, specific RNAs can be released from cancer cells into biofluids, allowing their identification and further determination of their potential value as biomarkers, as they may mirror the cellular state within the concept of liquid biopsy. For instance, some RNA transcripts were already evidenced and found increased in plasma, as is the case of telomerase reverse transcriptase (hTERT) that showed diagnostic and prognostic value for prostate cancer, being a good predictor of recurrence [35,36]. Similarly, the levels of the long non-coding RNA prostate cancer associated 3 (PCA3) were abundantly found in urine of patients with prostate cancer, constituting a promising non-invasive biomarker for the diagnosis of that cancer [37,38].…”

hTERT&nbsp;Represents an Innovative Bio-marker in Cholangiocarcinoma Detection

“…In gastric cancer, the expression pro le of hTERT showed close link with clinical factors and disease-free survival of the patients that might be a potential prognostic biomarker for the cancer [30]. The plasma hTERT mRNA level was signi cantly different between healthy individuals and prostate cancer cases, and ROC analysis demonstrated that hTERT was an useful non-invasive diagnostic biomarker for the disease [31]. Taken together, hTERT might be a potential molecular biomarker for human cancer that might be widely used for early detection, targeted treatment, and prognosis evaluation in tumor.…”