By Stephen Beech via SWNS
A new cancer “fingerprint” can improve early detection of potentially deadly tumors, say scientists.
Changes are detectable with “near-perfect” accuracy by portable scanners in just a few hours, according to a new study.
They explained that different types of cancer have unique molecular “fingerprints” that can be picked up using handheld scanners in just a few hours.
The Spanish research team says their findings, published in the journal Molecular Cell, set the foundation for creating new, non-invasive diagnostic tests that detect different cancers quicker and earlier than currently possible.
The study centers around the ribosome, the protein factories of a cell.
For decades, ribosomes were believed to have the same blueprint across the human body.
However, researchers discovered a hidden layer of complexity – tiny chemical modifications that vary between different tissues, developmental stages, and diseases.
Study lead author Professor Eva Novoa, of the Centre for Genomic Regulation (CRG) in Barcelona, said: “Our ribosomes are not all the same.
“They are specialized in different tissues and carry unique signatures that reflect what’s happening inside our bodies.
“These subtle differences can tell us a lot about health and disease.”
Ribosomes are made of proteins and a special type of RNA molecule called ribosomal RNA (rRNA).
Prof Novoa says rRNA molecules are the target of chemical modifications, affecting the ribosome’s function.
She said: “95% of human RNA is ribosomal RNA. They are very prevalent in our cells.”
The research team looked for all types of chemical modifications across human and mouse rRNA from different tissues including the brain, heart and liver.
They discovered that each tissue has a unique pattern of rRNA modifications – which they call an “epitranscriptomic fingerprint”.
Study first author Dr. Ivan Milenkovic said: “The fingerprint on a ribosome tells us where a cell comes from.
“It’s like each tissue leaves its address on a tag in case its cells end up in the lost and found.”
The researchers discovered different sets of fingerprints in diseased tissue samples from patients with cancer, particularly in the lung and testis.
Dr. Milenkovic said: “The cancer cells are ‘hypomodified’, meaning they constantly lose some of these chemical marks.
“We thought this could be a powerful biomarker.”
The research team looked at lung cancer more closely.
They obtained normal and diseased tissues from 20 patients with stage I or stage II lung cancer and confirmed that the rRNA from cancer cells is hypomodified.
The team used the data to train an algorithm that can classify the samples based solely on data from this unique molecular fingerprint.
The test achieved “near-perfect” accuracy in distinguishing between lung cancer and healthy tissue.
Dr. Milenkovic said: “Most lung cancers aren’t diagnosed until late stages of development.
“Here we could detect it much earlier than usual, which could one day help buy patients valuable time.”
The team said the study was possible thanks to a new technology called nanopore direct RNA sequencing, which permits the direct analysis of rRNA molecules with all its modifications.
Dr. Novoa said: “It allows us to see the modifications as they are, in their natural context.”
She explained that before the advent of nanopore sequencing, conventional techniques would process RNA molecules in such a way that it would remove the chemical modifications before researchers could study them.
Dr. Novoa said: “Scientists typically got rid of ribosomal RNAs because they saw it as redundant information that would get in the way of our experiments.
“Fast forward a few years, we’ve taken this data out of the junkyard and turned it into a gold mine, especially when information about chemical modifications is captured. It’s an incredible turnaround.”
She says the advantage of nanopore sequencing is that it relies on small, portable sequencing devices that can fit in the palm of a hand.
Researchers can insert biological samples into the machine, which captures and scans RNA molecules in real-time.
The study could distinguish cancer and normal cells by scanning as few as 250 RNA molecules obtained from tissue samples, a fraction of what a typical nanopore sequencing device is capable of.
Dr Novoa said: “It is feasible to develop a rapid, highly accurate test that looks for cancer’s ribosomal fingerprint using minimal amounts of tissue.”
In the long term, the researchers want to create a diagnostic method that can detect cancer’s fingerprint in circulating RNA in the blood.
That would be a less invasive approach because it would only require a blood sample rather than taking tissue samples from patients.
But the research team cautioned that more work is needed before the approach can be used for clinical benefits.
Dr. Milenkovic said: “We’re just scratching the surface.
“We need larger studies to validate these biomarkers across diverse populations and cancer types.”
The researchers said one of the main questions they are yet to explore is why the modifications change in cancer in the first place.
They say that if rRNA modifications are helping cells produce proteins that promote uncontrolled growth and survival, scientists could identify the mechanisms responsible for adding or removing the modifications, potentially leading to new ways of reversing harmful changes.
Dr. Novoa added: “We are slowly but surely unraveling this complexity.
“It’s only a matter of time before we can start understanding the language of the cell.”
