Single-Cell Sequencing Provides Insights into Ovarian Cancer Subtypes

Single-Cell Sequencing Provides Insights into Ovarian Cancer Subtypes
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New advances in single cell RNA sequencing technology has brought researchers from the UK closer to discovering the cellular origin of a multitude of ovarian cancer subtypes, which they hope will eventually allow for the development a screening tool and better treatment options for this silent killer of women.

Ovarian cancer is the fifth most common cancer in women in the United States, with approximately 21,750 women expected to be diagnosed in 2020, and another 14,000 women expected to die from this cancer due to late detection and poor treatment options.

Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system, and a woman’s risk of getting ovarian cancer during her lifetime is about 1 in 78. What makes this cancer so deadly is there is not general screening or diagnosis tool available, and the ovary is an internal organ that cannot be monitored for symptoms other than generalized abdominal pain and irregular menstrual cycles.

The development of screening tools has transformed survival rates for other cancers such as cervical and breast cancer, and researchers hope that once a screening tool has been developed for ovarian cancer, it can be caught in its earlier stages where treatment is easier and there is a lower risk for patient death.

Professor Ahmed Ashour Ahmed at the University of Oxford hopes to change the screening procedure by using modern technology to better understand changes in the ovary.  By using single cell RNA sequencing, where he can examine all the RNA molecules in an individual cell (more traditional techniques would look at groups of cells per assay) to monitor for specific changes in genetic expression for a particular ovary cell.

By doing so, he hopes to be able to identify biomarkers that are specific to the development of ovary cancer, and would be a marker clinicians would be looking for.

Ahmad and colleagues designed a study where researchers used single-cell sequencing to look at the RNA in individual normal cells from the inner layer (epithelium) of Fallopian tubes. This is the part of the female reproduction system that carry eggs from the ovaries to the uterus, and it is also the origin of the vast majority of ovarian cancers.  By isolating tissue (and furthermore individual cells from this tissue), the scientists were able to identify new subtypes of normal Fallopian tube cells.

The cells in the female reproductive system are constantly changing in response to hormone changes related to the menstrual cycle, so the cellular and tissue matter within them has several difference stages of normal, not all of which have been well documented.

Surprisingly, the molecular fingerprints of the subtypes that were identified had many genetic mirrors in individual ovarian cancers, which suggests that there may be many specific subtypes of ovarian cancer. Furthermore, the scientists discovered though single-cell sequencing from a normal Fallopian tube the identify a particular group of ovarian cancer patients with have the poorest chance of surviving the disease because they do not benefit from current treatments.

Focusing on developing new treatments for this particular group of patients can be an important way to improve overall survival rates, particularly once definitive numbers for this subtype of ovarian cancer can be established.

Ahmed said: “Identifying the type of cancer cells is an important early step in choosing which drugs and treatments to use because different types of cells respond differently to treatment. The “Oxford Classic”, our new tumor classifier, should give us much more accurate predictions for disease outcome in patients as well as helping us to develop targeted therapies for each type of cancer.”

Zhiyuan Hu, first author on the paper, said: “The discovery of new types of cells sheds new light onto the complexity of ovarian cancers. This research should take us a step closer to identifying the cell of origin of ovarian cancer and to developing a new tool for screening. It also opens the door for similar research for other types of cancers.”

Cary Wakefield, chief executive, said: “We fund world-class research to address the low survival rate women diagnosed with ovarian cancer currently face. These exciting findings take us closer to both a screening tool and personalized treatments, the two key elements we know will transform the lives of women diagnosed with ovarian cancer today and for generations to come.”

Hopefully, once all of the subtypes of ovarian cancer can be identified, it will be possible for scientists to develop personalized medicine strategies for treating this cancer, starting with screening for particular biomarkers, and concluding with the fast development of drugs designed to target the particular genetic mutations.