Cell-free RNA blood test identifies early-stage cancers, monitors treatment resistance and detects tissue damage

Stanford medicine researchers have developed a blood test capable of detection of cancer, the way cancer opposes treatment and tissue injury due to non-cancer conditions.

The new test analyzes RNA molecules in the bloodstream. This type of RNA is called cell-free RNA because small molecules no longer live in a cell. All types of tissues and organs in the entire body, including cancer tumors, are always pieces of DNA and RNA due to natural cell death of natural cell death.

Researchers spent more than six years in developing novel methods to target Messenger RNA in the blood and then used it to identify the presence of cancer in various stages, track cancer resistance to track resistance and monitor the severity of injury to healthy tissue.

“As archaeologists can learn about ancient societies, by studying the waste left behind, we can learn a lot about what is going on in the cells of a patient’s body, based on the RNA molecules cleaned through the blood,” co-author Maximilian din, MD, PhD, and Sam Wilson said. “We have developed a sensitive, versatile new type of liquid biopsy that measures cell-free and circulating-tumor RNA and has the ability to increase personal medicine in cancer and non-cancer diseases.”

A paper Cell-free RNA was published in interpretation of blood test method and applications Nature On April 16, 2025. Stanford Cancer Institute, a postdotoral scholar at the Stanford Cancer Institute, Monica Neslebash, Postdorle Scholars in Pathology, and a former postdotoral scholar in Stanford Medicine, who is a professor at the University of Sungkakwan, who is the first author. Ash Alizadeh, MD, PhD, Professor of Mogadam family and Professor of Medicine, Oncology and Hematology, led the study with Dine.

Resistance to cancer detection and treatment

The blood does not have too much cell-free RNA, and about 95% of it is ribosomal RNA that creates cellular structures that produce proteins. The new blood test analyzes Messenger RNA, which makes less than 5% of the cell-free RNA pool, as these molecules serve as a sign of which genes are expressed as proteins.

Researchers banned their analysis of gene expression in a group of about 5,000 genes that are usually not expressed in the blood of healthy people. Focusing on these so -called rare abundance genes increased the testing ability to correctly identify the cancer by a factor of 50. In the test, lung cancer RNA was found in 73% of lung cancer patients, which were involved in early stages.

“Analysis of rare abundance genes allows us to focus on the most relevant subgroups of RNA to detect the disease, such as archaeologists who want to learn what people eat, which can focus on the most of the artifacts like food containers or utensils,” Elizadeh said.

Detection of cell-free messenger RNA means that blood test is capable of monitoring conditions that do not include genetic mutations that are the basis of most DNA-based tests, such as some causes of cancer treatment resistance.

“Unfortunately, an important fraction of our patients who are being treated for cancer are stopped working, and this resistance is often based on adaptation that does not include genetic changes, but rather how cells behave or even the cells look under a microscope,” Alizadeh explained.

“Our non-invasive approaches have the ability to avoid surgical biopsy and identify these common types of resistors, before the burden of adequate disease was shown on the scan or presented with symptoms like pain, providing an opportunity to change treatment and improve results.”

Find a biomarker from what is in the freezer

Before the research team could read information from cell-free messenger RNA in the blood, they had to remove the effects of platelets, cells in the blood that are responsible for clots and are included in RNA but not DNA. To affect the results of the platelets and prevent signs from cancer, researchers developed a combination of molecular and computational strategies that reduce contribution from these several cells.

To overcome platelet contamination, a computational approach means that the method works on newly collected blood samples and samples that have been collected and stored earlier.

“This approach means that the test can currently be used to examine blood samples in the freezer from a complete clinical test, for example, and can help find a molecular signature that predicts to respond to a drug and who did not,” Dyhan said. “We can save time using historical samples to discover a biomarker that can be applied to patients later in real time.”

Snowfall

The new cell-free RNA method also provides useful information for non-cancer applications. The test detected high levels of normal lung RNA in blood samples from patients, which were intubted and on a ventilator for the treatment of acute respiratory crisis syndrome, a condition that causes severe damage to the lungs and causes cells to die.

The amount of normal lung RNA in blood samples from patients with covid-19 reflected how sick they were. Researchers also found normal lung RNA in the blood of smokers, which were healthy, possibly indicating micro injuries to the lungs due to smoking.

Researchers at Massachusetts General Hospital, Harvard Medical School, Memorial Slone Catering Cancer Center, Fred Hachinson Cancer Center and Washington University also contributed to the study.