scholarly journals Non-invasive detection of endometrial cancer by DNA methylation analysis in urine

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Rianne van den Helder ◽  
Birgit M. M. Wever ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Constantijne H. Mom ◽  
...  

Abstract Background The incidence of endometrial cancer is rising, and current diagnostics often require invasive biopsy procedures. Urine may offer an alternative sample type, which is easily accessible and allows repetitive self-sampling at home. Here, we set out to investigate the feasibility of endometrial cancer detection in urine using DNA methylation analysis. Results Urine samples of endometrial cancer patients (n = 42) and healthy controls (n = 46) were separated into three fractions (full void urine, urine sediment, and urine supernatant) and tested for three DNA methylation markers (GHSR, SST, ZIC1). Strong to very strong correlations (r = 0.77–0.92) were found amongst the different urine fractions. All DNA methylation markers showed increased methylation levels in patients as compared to controls, in all urine fractions. The highest diagnostic potential for endometrial cancer detection in urine was found in full void urine, with area under the receiver operating characteristic curve values ranging from 0.86 to 0.95. Conclusions This feasibility study demonstrates, for the first time, that DNA methylation analysis in urine could provide a non-invasive alternative for the detection of endometrial cancer. Further investigation is warranted to validate its clinical usefulness. Potential applications of this diagnostic approach include the screening of asymptomatic women, triaging women with postmenopausal bleeding symptoms, and monitoring women with increased endometrial cancer risk.

2019 ◽  
Vol 8 (12) ◽  
pp. 2107 ◽  
Author(s):  
Davide B. Gissi ◽  
Achille Tarsitano ◽  
Andrea Gabusi ◽  
Roberto Rossi ◽  
Giuseppe Attardo ◽  
...  

Background: This study aimed to evaluate the prognostic value of a non-invasive sampling procedure based on 13-gene DNA methylation analysis in the follow-up of patients previously treated for oral squamous cell carcinoma (OSCC). Methods: The study population included 49 consecutive patients treated for OSCC. Oral brushing sample collection was performed at two different times: before any cancer treatment in the tumor mass and during patient follow-up almost 6 months after OSCC treatment, within the regenerative area after OSCC resection. Each sample was considered positive or negative in relation to a predefined cut-off value. Results: Before any cancer treatment, 47/49 specimens exceeded the score and were considered as positive. Six months after OSCC resection, 16/49 specimens also had positive scores in the samples collected from the regenerative area. During the follow-up period, 7/49 patients developed locoregional relapse: 6/7 patients had a positive score in the regenerative area after OSCC resection. The presence of a positive score after oral cancer treatment was the most powerful variable related to the appearance of locoregional relapse. Conclusion: 13-gene DNA methylation analysis by oral brushing may have a clinical application as a prognostic non-invasive tool in the follow-up of patients surgically treated for OSCC.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Barbara C. Snoek ◽  
Annina P. van Splunter ◽  
Maaike C. G. Bleeker ◽  
Maartje C. van Ruiten ◽  
Daniëlle A. M. Heideman ◽  
...  

2014 ◽  
Vol 67 (12) ◽  
pp. 1067-1071 ◽  
Author(s):  
Lise M A De Strooper ◽  
Marjolein van Zummeren ◽  
Renske D M Steenbergen ◽  
Maaike C G Bleeker ◽  
Albertus T Hesselink ◽  
...  

AimsGene promoter hypermethylation is recognised as an essential early step in carcinogenesis, indicating important application areas for DNA methylation analysis in early cancer detection. The current study was set out to assess the performance of CADM1, MAL and miR124-2 methylation analysis in cervical scrapes for detection of cervical and endometrial cancer.MethodsA series of cervical scrapes of women with cervical (n=79) or endometrial (n=21) cancer, cervical intraepithelial neoplasia grade 3 (CIN3) (n=16) or CIN2 (n=32), and women without evidence of CIN2 or worse (n=120) were assessed for methylation of CADM1, MAL and miR124-2. Methylation analysis was done by the PreCursor-M assay, a multiplex quantitative methylation-specific PCR.ResultsAll samples of women with cervical cancer (79/79, 100%), independent of the histotype, and 76% (16/21; 95% CI 58.0% to 94.4%) of women with endometrial cancer scored positive for DNA methylation for at least one of the three genes. In women without cancer, methylation frequencies increased significantly with severity of disease from 19.2% (23/120; 95% CI 12.1% to 26.2%) in women without CIN2 or worse to 37.5% (12/32; 95% CI 20.7% to 54.3%) and 68.8% (11/16; 95% CI 46.0% to 91.5%) in women with CIN2 and CIN3, respectively. Overall methylation positivity and the number of methylated genes increased proportionally to the lesion severity.ConclusionsDNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer and the majority of CIN3 lesions, and has the capacity to broaden its use on cervical scrapes through the detection of a substantial subset of endometrial carcinomas.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masaru Nagashima ◽  
Naofumi Miwa ◽  
Hajime Hirasawa ◽  
Yukiko Katagiri ◽  
Ken Takamatsu ◽  
...  

Proceedings ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 32
Author(s):  
Morselli ◽  
Rossi ◽  
Morandi ◽  
Tarsitano ◽  
Gabusi ◽  
...  

Patients treated for Oral Squamous Cell Carcinoma (OSCC) showed a significant risk todevelop a loco-regional relapse during follow-up period. [...]


Proceedings ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 27
Author(s):  
Gissi ◽  
Romeo ◽  
Tenore ◽  
Pentenero ◽  
Campisi ◽  
...  

In a recent study our research group described a non-invasive sampling procedure based on [...]


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Bach ◽  
I. Paulis ◽  
N. R. Sluiter ◽  
M. Tibbesma ◽  
I. Martin ◽  
...  

AbstractColorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p < 0.0001). Methylation analysis in unfractioned urine appeared inaccurate. Following multivariate logistic regression and classification and regression tree analysis, a marker panel consisting of SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.


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