Malignancy criterion

The number of genes that are used to synthesize RNA has helped scientists detect dangerous cancer cells

Polina Gershberg, Naked Science

Doctors from Stanford University have shown that the number of genes that are used to build RNA molecules is a reliable marker of the "maturity" of a cell. This discovery can greatly simplify the search for genes responsible for the development of cancer.

The cells that initiate the development of cancerous tumors belong to stem cells. They can develop and differentiate into more developed structures, forming body tissues. Or, if something goes wrong, turn into cancerous. As stem cells become more "mature" and specialized, they express fewer and fewer genes

"Currently, targeted therapy is aimed at specific genes or molecules, the vast majority of which may not be specific to cancer stem cells," says Aaron Newman, one of the authors of a paper published in Science (Gulati et al., Single–cell transcriptional diversity is a hallmark of developmental potential). – Such methods usually do not work for long. But if it is possible to identify the least differentiated cells and then look for markers specific to them, this is no longer a guessing game."

Together with his colleagues, Newman combined the processes of counting expressed genes in cells with measuring the number of RNA copies per gene. Based on these data, a computer algorithm called CytoTRACE was created, which is able to determine the degree of cell maturity.

Data from various gene counts obtained and visualized using CytoTRACE / © CytoTRACE.

Cancerous tumors can contain many millions of cells, each of which contains thousands of gene mutations. Most of these cells are differentiated and die naturally. A smaller part is more dangerous cancer stem cells that initiate the appearance of a tumor. They are responsible for resistance to treatment, metastasis and relapses. With the help of existing methods, such cells are difficult to detect, but with the help of CytoTRACE it is much easier to find them. An algorithm that analyzes data on all RNAs synthesized in a single cell can quickly repeat a study that takes years using traditional methods.

"The way we are now finding cell markers for cancer stem cells is to make educated guesses about which markers are likely to be important, and then sort these cells and track the activity of stem cells," says one of the authors of the article, Michael Clarke, who was the first to discover cancer stem cells in a solid tumor. "CytoTRACE allows us to first find stem cells or progenitor cells, and then see what unique markers they have."

In the article, the researchers describe the use of an algorithm for RNA data in one cell of thrice-negative breast cancer. This disease is dangerous because tumor growth does not depend on those biochemical pathways that are usually the target for treatment. CytoTRACE not only identified known markers of cancer stem cells, but also discovered a marker that was not previously considered important.

According to Newman, CytoTRACE is able to revolutionize the methods of stem cell research associated with other diseases. "This tool can also be useful in finding ways to treat Alzheimer's disease or other degenerative diseases in which the loss of stem cell function may be part of the pathological process," says the scientist.

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