A new study, published yesterday in Nature Communications, has found that the DNA methylation of cells collected during cervical smear tests can be used to detect ovarian cancer.
Ovarian cancer is the sixth most common cancer in women in the UK and the most common cause of gynaecological cancer-associated deaths. In addition, 75% of ovarian cancers are diagnosed at a late stage when the tumours have already spread. If the cancer could be detected earlier, the chance of treatment being successful would be much higher. As such, there is a clear need for an approach that can identify women at the highest risk of developing ovarian cancer.
Previous research has suggested that predisposition to ovarian cancer is associated with changes in DNA methylation patterns. To investigate this further, the team behind the current study analysed epigenetic changes in cervical smear samples from women with ovarian cancer.
Analysing DNA methylation patterns
First, the team analysed the epigenome of cervical cell samples from 242 women with ovarian cancer and 869 women without cancer. In total, the team analysed 14,000 CpG sites and found that 91 were significantly differentially methylated between the samples.
The researchers found that women at a higher risk of ovarian cancer had specific DNA methylation signatures. These women had a much lower frequency than controls of CpG islands (CpG rich regions of DNA). Instead, most of the CpG sites in the cancerous DNA samples were isolated. The team then used statistical methods to classify samples as either cancerous or controls. From this data, the scientists created the Women’s Risk Identification for Ovarian Cancer index (WID-OC index). The higher the index number, the higher the risk of cancer.
Predicting presence of ovarian cancer
Next, the team tested the performance of the WID-OC test. They found that it identified 71.4% of women under 50 and 54.5% of women over 50 in the study cohort with ovarian cancer with 75% specificity. The researchers further validated the findings in an external cohort. In addition, the test was able to discriminate between cases and controls in samples with no tumour DNA present. This suggests that it was the methylation signatures and not tumour DNA that was driving the test results.
Next, the team tested the WID-OC index on healthy women who were known to have an extremely high probability of developing ovarian cancer in the future. These women carried the BRCA1 gene mutation. Individuals who have a BRCA1 gene mutation are at an increased risk of multiple cancers, including breast and ovarian cancer. Interestingly, the team found that the WID-OC index gave back high numbers for these women. This finding supports the clinically well-known link between breast and ovarian cancer predisposition.
Future and importance
Altogether, the findings of this study show a strong association between epigenetic differences and cancer risk. This indicates that epigenetic signatures may hold the key to early detection of ovarian cancer. However, further work has to be done. Scientists will need to carry out studies in larger cohorts to properly assess the validity of the WID-OC index.
Despite this, the test developed in this study is, to date, the best performing ovarian cancer risk prediction model. In the future, the researchers hope to harness the test to provide early detection and therefore, early treatment to cancer patients.
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