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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.

Background: The non-invasive diagnostic approach for early detection of endometrial cancer (EC) remains limited. To date, human epididymis protein 4 (HE4) has been intensively studied but its diagnostic is controversial in EC. DJ-1 is an oncoprotein secreted by cancer cells, recently identified as a potential diagnostic biomarker for breast cancer, melanoma, and pancreatic cancer. The aim of this study was to compare the diagnostic performances of DJ-1 and HE4 measured in EC patients and healthy controls (HC)., Methods: Forty-five patients (63.9±12.0 years) with EC and 29 (63.2±13.3 years) HC were enrolled. Serum concentrations of DJ-1 and HE4 were measured using ELISA kits developed by R&D (Minneapolis, USA) and Fujirebio Diagnostic (Malvern, PA, USA), respectively. Differences between EC patients and HC were assessed by Mann-Whitney test and associations were tested by Spearman's correlation. The diagnostic performance was assessed using receiver operating characteristics (ROC) curves analysis., Results: Serum DJ-1 concentrations were found to be higher in EC patients than in HC (9533.6 vs 1988.5 pg/mL; P<.0001). The area under the ROC curve (ROC-AUC) was 0.95 (P<.0001). At the cut-off of 3654 pg/mL, the sensitivity and specificity were 0.89 and 0.90, respectively. HE4 serum levels were higher in EC patients than in HC (75.3 vs 56.2 pmol/L; P=.019), with an AUC of 0.66 (P=.020). The AUC obtained by the combination of the two markers resulted 0.96 (P<.0001)., Conclusion: These results suggest that increased serum DJ-1 levels are associated with EC and that this biomarker may be potentially useful for diagnosing EC., (© 2017 Wiley Periodicals, Inc.)

Background: Endometrial cancer (EC) is currently considered the fourth most frequent female cancer in Europe. In an attempt to achieve an early diagnosis, many studies have identified some putative biomarkers for gynecologic cancers, including circulating microRNAs (miRs) and aberrant promoter methylation status. Previous studies which have investigated miR-203 expression profiles in EC tissues and normal endometrial tissues concluded that miR-203 is regulated by methylation promoter. The aim of this study was to investigate the expression of miR-203 and promoter methylation levels in serum of EC patients and healthy controls (HC)., Methods: Forty-five EC patients (64 ± 12 years) and 30 HC (63 ± 13 years) were enrolled before undergoing therapeutic procedures. RNA extraction from serum was performed with mirVana PARIS Isolation Kit (Thermo Scientific). miR expression was assessed by quantitative RT-PCR (Applied Biosystems). The expression levels of miR were normalized to miR-16 and calculated using the 2-ΔCt method. A quantitative methylation-specific PCR (MSP) technique was used to analyze miR-203 promoter methylation status. Differences between groups were assessed by Mann-Whitney test (for continuous variables) and chi-squared test (for categorical variables), whereas the correlation was calculated using Spearman's test. The diagnostic performance of miR-203 was defined using receiver operator characteristic (ROC) curves., Results: Serum expression levels of miR-203 were higher in EC patients compared to HC (p = 0.002). Aberrant miR-203 methylation was detected in 11/45 (24.4%) EC patients and in 2/30 (6.6%) HC (p = 0.046). The expression levels of miR-203 were not significantly correlated with promoter methylation status. The area under the curve of miR-203 expression was 0.71 (p = 0.002)., Conclusions: The high circulating miR-203 expression levels in EC patients compared to HC confirm the role of this miR as a potential biomarker for diagnosis of EC. Aberrant miR-203 methylation assessed in the peripheral blood does not apparently reflect cancer biology.

Objective: Current evidence suggests that no single serum biomarker displays satisfactory diagnostic performance in patients with endometrial carcinoma (EC), the most frequent gynecological cancer in developed countries. However, aberrant tissue microRNA (miRNA) expression has been recently described in EC. Therefore, this study aimed to investigate the differential expression of 4 serum miRNAs and their association with CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) in EC patients and in a control population., Methods: Forty-six consecutive women with EC and 28 matched control subjects without a history of cancer or other diseases were enrolled. Total serum RNA was extracted using mirVana PARIS Kit. TaqMan MicroRNA Assay was used for quantitative real-time reverse transcriptase-polymerase chain reaction on ABI 7500 Sequence Detection System to assess differential miRNAs expression. The relative expression levels of 4 miRNAs (miR-222, miR-223, miR-186, and miR-204) were normalized to miR-16 and calculated using the 2-△Ct approach., Results: Serum levels of miR-186, miR-222, and miR-223 appeared to be significantly higher in patients compared with control subjects (P = 0.004, P = 0.002, and P < 0.0001). Contrarily, serum miR-204 was found to be significantly lower in EC patients (P < 0.0001). The diagnostic performance of miRNAs was found to be significantly better than that of CA125. Among the various biomarker tested, serum miR-204 and HE4 exhibited the best diagnostic performance for discriminating EC patients from control subjects., Conclusions: These results underpin that the 4 miRNAs that we have investigated are implicated in development and progression of EC, thus opening new avenues in EC diagnostics.