Ovarian cancer is the deadliest disease among all gynecological disorders. A recent study, under the supervision of York Research Chair and Faculty of Science Professor Chun Peng and led by PhD student Mohamed Salem, offers novel insight into the complex regulatory mechanisms that are involved in the development of ovarian cancer.
“Our study provides strong new evidence to support a tumour-promoting role of a microRNA, miR-590-3p, in ovarian cancer. We found that miR-590-3p levels are higher in more aggressive tumour tissues when compared to less aggressive tumours. We also identified a gene named Forkhead Box A2 (FOXA2) as a target of miR-590-3p. We provided several lines of evidence to support the idea that FOXA2 inhibits tumour growth in ovarian cancer,” Peng said.
In fact, high levels of FOXA2 in ovarian cancer tumours correlate with improved survival. “This suggests that this gene may be a prognostic marker for this deadly disease,” Salem added. “On the other hand, miR-590-3p levels are higher in the blood of ovarian cancer patients when compared to women with benign gynecological disorders.” This means that miR-590-3p may be a useful marker for earlier detection, which could improve patient outcomes and save lives.
This study, which was funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation/Ontario Research Fund, was published in Cancer Research (2018).
Ovarian cancer survival rates comparatively lower, detection difficult
Ovarian cancer is arguably one of the most serious women’s cancers because the survival rate is lower than other common cancers of the female reproductive system (Statistics Canada). The five-year survival rate is 45 per cent. An estimated 2,800 Canadian women will be diagnosed with this cancer in 2019 (Ovarian Cancer Canada/OCC).
This research is particularly relevant and promising because ovarian cancer is difficult to detect for the following reasons:
- Some symptoms, such as indigestion, bloating or frequency in urinating, are vague and can be mistakenly attributed to other causes.
- A pelvic exam, transvaginal ultrasound or cancer antigen 125 (CA125) test could help to find ovarian cancer, according to the Canadian Cancer Society, but there is no reliable screening test for it (OCC).
- The only way to diagnose it is through surgery or a biopsy (OCC).
Depending on the stage and type of the cancer and the size of the tumour, various treatments are available. These include surgery to remove the tumour, chemotherapy to shrink the tumour before surgery or to destroy the remaining cancer cells after surgery, or radiation in some cases.
Study focused on the most common form of ovarian cancer
The goal of this study was to investigate the role of miR-590-3p in the development of ovarian cancer. The research team focused on epithelial ovarian cancer (EOC), the most common form of this cancer, which has the highest mortality rate among all gynecologic malignancies.
Two sets of samples (tumours) were used in the study: the first was collected at the Mansoura Oncology Center in Egypt, and the second was obtained from the Ottawa Ovarian Cancer Tissue Bank.
For the first set of samples, control ovarian tissues were taken from women who underwent hysterectomy and/or oophorectomy for benign gynecologic conditions, as a point of comparison. Blood samples were also collected prior to surgery. These samples were used to measure miR-590-3p and FOXA2 levels.
To investigate the role of miR-590-3p in ovarian cancer development, researchers increased the level of miR-590-3p in ovarian cancer cells and observed how tumours were formed and metastasized. They also conducted studies on culture plates and measured cancer cell behaviours when cells have an increased or decreased level of miR-590-3p.
Key findings could lead to improved outcomes, possibly save lives
This study provided original new evidence regarding miR-590-3p and its role in promoting the development of ovarian cancer. “We demonstrated that overexpression of miR-590-3p significantly increased cell proliferation, migration, invasion and colony formation in vitro – that is, outside a living organism,” Salem explained. “We also found that mir-590 promoted tumour growth and metastasis in vivo – inside a living organism,” he added.
The team found that miR-590-3p levels were significantly elevated in EOC tumours when compared with normal ovaries, and miR-590-3p plasma levels were higher in patients with EOC than in subjects with benign gynecologic disorders. “These findings suggest that higher miR-590-3p is associated with a more aggressive disease,” Salem explained.
The researchers also discovered the following:
- FOXA2 inhibits versican, a matrix protein that is important for the spreading of ovarian cancer cells into other organs;
- FOXA2 plays a tumour-suppressive role in EOC;
- FOXA2 expression is associated with a less aggressive disease; and
- Patients who have a high level of FOXA2 and a lower level of versican may have a better chance for survival.
The new findings reported in this paper could lead to the development of new markers for ovarian cancer – allowing for earlier detection – and this could save lives.
This article was originally published on March 1, 2019 by York University, Research & Innovation.