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Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer

  • Original Article
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Pathology & Oncology Research

Abstract

To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p < 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79–0.95, p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI: 64.35–90.95) and a specificity of 80.65% (95% CI: 62.53–92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.

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Authors and Affiliations

  1. Section of Clinical Biochemistry, University of Verona, Verona, Italy

    Marco Benati, Martina Montagnana, Elisa Danese, Elisa Paviati & Giuseppe Lippi

  2. Laboratory of Clinical Chemistry and Hematology, AOUI Verona, Verona, Italy

    Martina Mazzon

  3. Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, Varese, 21100, Italy

    Simone Garzon, Antonio Simone Laganà, Jvan Casarin & Fabio Ghezzi

  4. Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Verona, Italy

    Silvia Giudici, Ricciarda Raffaelli & Massimo Franchi

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Contributions

G Lippi, M Franchi, F Ghezzi, M Benati and M Montagnana: study conceptualization, and protocol planning. M Benati, E Danese, M Mazzon, E Paviati and M Montagnana: laboratory analysis, data extraction, and statistical analysis. S Garzon, AS Laganà, J Casarin, S Giudici and R Raffaelli: clinical evaluation, follow-ups, data collection, and statistical analysis. G Lippi, F Ghezzi, M Franchi and M Montagnana: project administration, methodology validation, and supervision. S Garzon, AS Laganà, M Benati and M Montagnana: Manuscript writing/editing. G Lippi, F Ghezzi, M Franchi: Manuscript revision and final approval. All the authors conform the International Committee of Medical Journal Editors (ICMJE) criteria for authorship, contributed to the intellectual content of the study and gave approval for the final version of the article.

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Correspondence to Simone Garzon.

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Benati, M., Montagnana, M., Danese, E. et al. Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer. Pathol. Oncol. Res. 26, 2281–2289 (2020). https://doi.org/10.1007/s12253-020-00819-x

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