Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in En
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ORIGINAL ARTICLE
Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer Marco Benati 1 & Martina Montagnana 1 & Elisa Danese 1 & Martina Mazzon 2 & Elisa Paviati 1 & Simone Garzon 3 & Antonio Simone Laganà 3 & Jvan Casarin 3 & Silvia Giudici 4 & Ricciarda Raffaelli 4 & Fabio Ghezzi 3 & Massimo Franchi 4 & Giuseppe Lippi 1 Received: 25 July 2019 / Accepted: 12 May 2020 # Arányi Lajos Foundation 2020
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. Keywords Endometrial cancer . Endometrial hyperplasia . cfDNA . Telomere length . Diagnosis . Biomarkers
Introduction Endometrial cancer (EC) represents the most common gynecologic malignancy in developed countries, with an age-
* Simone Garzon [email protected] 1
Section of Clinical Biochemistry, University of Verona, Verona, Italy
2
Laboratory of Clinical Chemistry and Hematology, AOUI Verona, Verona, Italy
3
Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, Varese 21100, Italy
4
Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Verona, Italy
standardized incidence of approximately 13.6 per 100,000 women [1]. The prognosis of this cancer is usually favorable in the early stage, with a 5-year overall survival rate approximating 80–90%, but it decreases to 5
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