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Developmental Biology - Ovarian Cancer

Closing In On Cell of Origin For Ovarian Cancer

New technique identifies previously unknown cell types in human fallopian tubes...


Researchers at the University of Oxford, UK, are now closer to finding the cell of origin in ovarian cancer. Their ultimate aim is to develop a much needed screening tool for its early detection.

Ovarian cancer is the sixth most common cancer in women. Around 7,500 new cases are diagnosed in the UK each year. Currently only 35% of patients in England will live 5 years beyond their diagnosis, as less than 1 in 3 patients are diagnosed at Stage 1 where survival rates are as good as 95%.
Development of better screening tools has transformed survival rates for cervical and breast cancer. In the current study, researchers used single-cell sequencing to examine RNA in all individual normal cells found in the inner layer of epithelial cells lining both fallopian tubes.

Fallopian tubes carry eggs from the ovaries to the uterus, and are the point of origin of a vast majority of ovarian cancers. Examining RNA using single-cell sequencing, enables the identification of new subtypes of normal Fallopian tube cells. Surprisingly, the molecular fingerprint of these subtypes are mirrored in individual ovarian cancers.
Scientists discovered that single cell sequencing of normal Fallopian tubes can identify a particular group of ovarian cancer patients with the poorest chance of survival from current treatments. Focussing on new treatments for this group of patients will improve overall survival rates.

"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 the development of a new tool for screening. It also opens the door for similar research for other types of cancers," explains Zhiyuan Hu, first author on the paper.

This new research is published in the journal Cancer Cell

Highlights
The projection of FTE subtypes refines the molecular classification of SOC

Comprehensive single-cell profiling of FTE cells identifies six molecular subtypes

Substantial non-genetic heterogeneity of HGSOC identified in 1,700 tumors

A mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis.

Summary
The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ~6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ~1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.

Authors
Zhiyuan Hu, Mar Artibani, Abdulkhaliq Alsaadi, Nina Wietek, Matteo Morotti, Tingyan Shi, Zhe Zhong, Laura Santana Gonzalez, Salma El-Sahhar, Mohammad Karami Nejad Ranjbar, Garry Mallett, Yun Feng, Kenta Masuda, Yiyan Zheng, Kay Chong, Stephen Damato, Sunanda Dhar, Leticia Campo, Riccardo Garruto Campanile, Hooman Soleymani majd, Vikram Rai, David Maldonado-Perez, Stephanie Jones, Vincenzo Cerundolo, Tatjana Sauka-Spengler, Christopher Yau and Ahmed Ashour Ahmed.


Acknowledgements
Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine and life sciences, and it is home to the UK's top-ranked medical school. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

Ovarian Cancer Action is working towards a world where no woman dies of ovarian cancer. We're investing millions in research projects across three vital areas: prevention, early diagnosis and more effective treatments. Improvements in each of these areas will transform the lives of women today and for generations to come. Help us change the future for the women we love.


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Feb 19 2020   Fetal Timeline   Maternal Timeline   News 



Using single-cell sequencing to examine RNA in every normal (epithelial) cell lining
both fallopian tubes, researchers are better able to distinguish Ovarian Cancer.
CREDIT Oxford University.


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