‘Holy grail’ of blood tests on the horizon after scientists find cancer alters RNA ‘dark matter’
SANTA CRUZ, Calif. — A “holy grail” blood test that can diagnose any type of cancer years before symptoms appear could be on the horizon. Scientists from UC Santa Cruz have discovered a protein released in the early stages of the disease, when tumors are most curable.
This key genetic change alters a patient’s RNA “dark matter” — creating a previously undiscovered biomarker in the genome which doctors can spot. Researchers say a gene named KRAS produces this protein, adding that it’s the most frequent mutation across all tumors, including lung, bowel, and pancreatic cancer.
The breakthrough offers hope of a simple screening program for at-risk individuals, such as older or genetically susceptible people. It would work by looking for chemical changes in fragments of genetic code that leak from tumors into the bloodstream.
“The sooner you detect that someone has cancer, the more likely they will be to survive through treatment and surgery,” says lead author Dr. Daniel Kim in a media release.
“Millions of people die from cancer every year around the world, and there is an urgent need to develop highly sensitive and specific diagnostic tests that enable cancer early detection, before it has spread to other parts of the body.”
What does KRAS do?
The KRAS gene regulates RNA (ribonucleic acid), molecules that “translate” instructions encoded in our DNA. Lab experiments found cancer-triggering variants wrongly activate others that doctors can detect in the blood through genetic sequencing.
Dr. Kim believes it is a very promising tool for diagnosing cancer in its earliest stages. Scientists could accomplish this using a minimally invasive technique called liquid biopsy, rather than traditional tumor tissue surgeries.
Some tumors shed DNA into the blood long before a person starts experiencing symptoms. According to the American Cancer Society, 1.9 million people in the United States received a cancer diagnosis in 2021. Over 600,000 died from the disease.
In Petri dishes, the researchers introduced mutant KRAS genes into healthy lung cells, pushing them into a cancerous state. They then performed RNA sequencing using several different methods. Computer simulations identified prevalent RNA compared to control cells.
Additional epigenomic profiling looked at how genes turn on or off without changes to the DNA sequence itself. Other tests identified which RNA strands are packaged into extracellular vesicles and preferentially secreted from cancerous cells affected by mutant KRAS.
“We were in an interdisciplinary environment that really encouraged us to think about RNA and cancer in a different way,” notes first author Roman Reggiardo, a PhD candidate in Dr Kim’s lab.
Designing a one-size-fits-all test for cancer
The researchers plan to confirm the results by analyzing blood samples from lung cancer patients. They hope to develop a test that could detect these RNA signatures as biomarkers for the early diagnosis of the disease. Additionally, they anticipate this work leading to a framework for developing an RNA liquid biopsy platform for multi-cancer early detection.
“Now that we know the RNA signatures of this very early event in cancer, this will help us develop new methods for cancer early detection, which will hopefully help save a lot of people’s lives in the future,” Kim says.
Scientists consider a one-size-fits-all test the “holy grail” of cancer research. It would augment rather than replace screening programs currently run by government health agencies, such as those for breast and cervical cancer.
It could also be particularly effective at finding tumors that can be difficult to identify early on, such as those of the bowel, lung, pancreas, throat, and ovaries.
The study is published in the journal Cell Reports.
South West News Service writer Mark Waghorn contributed to this report.
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