In a new study published in The American Journal of Pathology, scientists say they have identified a biomarker in patients with stomach cancer that starves tumors of their blood supply and reduces the ability of cancer cells to spread to other parts of the body.
The new research from China shows that stomach cancer patients whosecancer lesions show high levels of the biomarker microRNA 506 (miR-506) have far longer survival times compared with stomach cancer patients with lower levels of miR-506. Thus, miR-506 is a valuable biomarker to predict stomach cancer survival.
Other benefits of miR-506 include its ability to suppress tumor growth, blood vessel formation and the spread of cancer cells to other parts of the body.
Lead investigator Dr. Xin Song, of the Cancer Research Institute of Southern Medical University and the Cancer Biotherapy Center of The Third Affiliated Hospital of Kunming Medical University – both in China – says that “these findings indicate that miR-506 is necessary and sufficient for angiogenesis suppression during gastric cancer progression.”
In the US, stomach cancer, also known as gastric cancer, most commonly affects older people – around 60% of those diagnosed each year are over 65. Stomach cancer is most common in less developed countries. It is a primary cause of cancer-related deaths worldwide.
Study hypothesis developed from understanding the biochemical mechanisms
By way of introducing their research into stomach cancer, the authors begin by explaining that Epithelial-mesenchymal transition (EMT) in cancer cells is associated with an increased capacity to invade into surrounding tissue and migrate to distant sites.
Fast facts about stomach cancer
- Stomach cancer is more common in men than in women
- Stomach cancers tend to develop slowly over many years
- The overall 5-year relative survival rate of all people with stomach cancer in the US is about 29%.
EMT is a key step during normal embryo formation (embryogenesis), but EMT is now also recognized to be involved in processes within the body that result in functional changes associated with cancer (cancer pathophysiology).
While tumor-specific factors that drive EMT are not completely understood, it is known that various biochemical changes take place through EMT to produce “healing-type cells” called mesenchymal cells (MSCs).
In turn, it is MSCs that play an important role both in normal tissue repair as well as disease-causing processes, including tumor growth and the spread of cancer cells.
These transformed cells have the ability to migrate away from the tissues that line the cavities and surfaces of blood vessels and organs throughout the body, invade other tissues and stave off normal programmed cell death (PCD).
One of the several mechanisms that may initiate an EMT is the change in the expression of a specific class of small noncoding RNAs that regulate gene expression. It was one of these – miR-506 – that was identified by the researchers as a useful marker that enabled them to organize the patients they were studying in order of the severity of their stomach cancer.
Dr. Song says the research team considered the hypothesis that miR-506 acts as a suppressor of how cancer cells spread using a system level and integrative approach.
Tumor samples taken from people who had undergone cancer surgery
In a blind test, the researchers used a form of genetic analysis called polymerone chain reaction (PCR) to detect miR-506 in human gastric samples taken from 84 people who had undergone cancer surgery. The researchers analyzed the miR-506 levels in each of these samples, and patients were allocated to different groups based on whether they were above or below the mean miR-506 level.
This is when the team found that survival among patients with signs of high miR-506 was significantly longer.
At 60 months, for example, cumulative survival was approximately 30% in the low-miR-506 expression group, compared with 80% in the high-expression group.
The research team then looked at signs of miR-506 in seven stomach cancer cell lines. Here, it was found that stomach cancer cells had lower levels of miR-506 than normal stomach tissue.
Analysis of cells grown in vitro then showed that miR-506 levels were lowest in the cell lines that had the highest invasive activity, and the highest levels were seen in cell lines with the lowest invasive activity.
Further research and experiments strengthened the hypothesis that miR-506 acts as a suppressor of how cancer cells spread.
Commenting on the findings, Dr. Song says:
“In summary, cancer is a complex disease and controlling cancer development and progression requires system level and integrative approaches. Our study suggests that miR-506 acts as a tumor suppressor in gastric cancer.”
He adds that “additional studies will be needed to explore the potential clinical utility of miR-506 as a potential biomarker for gastric cancer prognosis and as a new potential therapeutic target.”
In April, Medical News Today, reported how researchers had created a breath test that could be used to diagnose stomach cancer.
Written by Jonathan Vernon