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. 2024 May 16;4(1):88.
doi: 10.1038/s43856-024-00517-8.

Molecular analysis for ovarian cancer detection in patient-friendly samples

Birgit M M Wever  1   2 , Mirte Schaafsma  1   2   3 , Maaike C G Bleeker  1   2 , Yara van den Burgt  1   2 , Rianne van den Helder  1   2   3 , Christianne A R Lok  3 , Frederike Dijk  2   4 , Ymke van der Pol  1   2 , Florent Mouliere  1   2 , Norbert Moldovan  1   2 , Nienke E van Trommel  3 , Renske D M Steenbergen  5   6
Affiliations

Molecular analysis for ovarian cancer detection in patient-friendly samples

Birgit M M Wever et al. Commun Med (Lond). .

Abstract

Background: High ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection.

Methods: Home-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n = 25, malignant n = 29). All samples were tested for nine methylation markers, using quantitative methylation-specific PCRs that were verified on ovarian tissue samples, and compared to non-paired patient-friendly samples of 110 age-matched healthy controls. Copy number analysis was performed on a subset of urine samples of ovarian cancer patients by shallow whole-genome sequencing.

Results: Three methylation markers are significantly elevated in full void urine of ovarian cancer patients as compared to healthy controls (C2CD4D, P = 0.008; CDO1, P = 0.022; MAL, P = 0.008), of which two are also discriminatory in cervical scrapes (C2CD4D, P = 0.001; CDO1, P = 0.004). When comparing benign and malignant ovarian masses, GHSR shows significantly elevated methylation levels in the urine sediment of ovarian cancer patients (P = 0.024). Other methylation markers demonstrate comparably high methylation levels in benign and malignant ovarian masses. Cervicovaginal self-samples show no elevated methylation levels in patients with ovarian masses as compared to healthy controls. Copy number changes are identified in 4 out of 23 urine samples of ovarian cancer patients.

Conclusions: Our study reveals increased methylation levels of ovarian cancer-associated genes and copy number aberrations in the urine of ovarian cancer patients. Our findings support continued research into urine biomarkers for ovarian cancer detection and highlight the importance of including benign ovarian masses in future studies to develop a clinically useful test.

Plain language summary

Ovarian cancer is often found late with limited treatment options. Currently, it is difficult to diagnose ovarian cancer correctly and no recommended early detection or screening methods exist. Our aim was to explore the use of DNA-based tests in patient-friendly samples for ovarian cancer detection. Patient-friendly samples are patient materials that can be collected from home without pain or discomfort, such as self-collected vaginal swabs and urine. Using DNA-based tests, we found that urine of women with ovarian cancer contains ovarian cancer-associated signals. Our findings encourage further development of a potential urine test for ovarian cancer detection. This approach could aid early detection and guide women with ovarian masses to appropriate specialist care.

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Conflict of interest statement

R.D.M.S. is a minority shareholder of Self-screen BV. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Study flowchart illustrating samples included in the methylation analysis and shallow whole-genome sequencing.
HGSOC high-grade serous ovarian cancer, SCNA somatic copy number aberrations, qMSP quantitative methylation-specific PCR.
Fig. 2
Fig. 2. Methylation levels of most discriminating markers C2CD4D, CDO1, GHSR, and MAL in full void (unfractionated) urine, urine supernatant, urine sediment, cervicovaginal self-samples, and clinician-taken cervical scrapes of healthy controls and patients diagnosed with a benign or malignant ovarian mass.
Methylation levels are expressed by 2log-transformed Cq ratios. Violin plots represent medians with lower and upper quartile and range whiskers. P values shown are Bonferroni corrected (i.e., divided by the number of diagnostic groups compared) and considered statistically significant when <0.05.
Fig. 3
Fig. 3. Genome-wide somatic copy number profiles of urine supernatant samples.
Panels show illustrative examples of patients with a stage IIIA carcinosarcoma (a), stage IIIC serous carcinoma (b), and a healthy control (c). Estimated ploidy and tumor fraction are listed at the top of the plot. The y axis depicts the log2 tumor to normal ratio.
See this image and copyright information in PMC

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