Molecular ‘fingerprints’ could be key to early cancer detection

Breakthrough research from the Center for Genomic Regulation (CRG) in Barcelona has revealed that different types of cancer leave distinct molecular “fingerprints” detectable in their early stages. 

These fingerprints, embedded in the ribosomes of cells, can now be identified with near-perfect accuracy using small, portable devices in just a few hours. 

Published in Molecular Cell, this discovery paves the way for creating revolutionary non-invasive diagnostic tests capable of detecting cancer faster and earlier than ever before.

Ribosomes and their hidden complexity

The study focuses on ribosomes, the cellular machinery responsible for protein production. Long believed to share a uniform structure across the human body, ribosomes have now been shown to possess a hidden layer of complexity. 

The researchers discovered tiny chemical modifications on ribosomal RNA (rRNA) molecules that vary by tissue type, developmental stage, and disease state.

“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,” explained study senior author Eva Novoa, a researcher at the Center for Genomic Regulation.

Molecular fingerprints, cellular health, and disease

Ribosomes consist of proteins and rRNA, with rRNA accounting for a staggering 95% of the total RNA in human cells. 

These molecules undergo chemical modifications that influence ribosomal function, creating unique “epitranscriptomic fingerprints” specific to different tissues. 

The researchers analyzed rRNA from human and mouse samples taken from organs such as the brain, heart, liver, and testis. They found that these fingerprints could provide a wealth of information about cellular health and disease.

The molecular signature of cancer

The study demonstrated that cancer cells have distinct rRNA fingerprints, particularly in cases of lung and testicular cancers. 

“The cancer cells are ‘hypomodified,’ meaning they constantly lose some of these chemical marks,” said lead author Ivan Milenkovic, a postdoctoral fellow at CGR. “We thought this could be a powerful biomarker.”

To test this hypothesis, the team examined tissue samples from 20 patients with early-stage lung cancer. They confirmed that rRNA in cancerous cells consistently exhibited hypomodifications. 

Fingerprints for early cancer detection 

Using these unique signatures, the researchers developed an algorithm capable of distinguishing cancerous from healthy tissue. This model achieved near-perfect accuracy, marking a significant advance in the quest for early cancer detection.

“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,” Milenkovic explained.

Breakthrough technology: Nanopore sequencing

The research was made possible by nanopore direct RNA sequencing, a cutting-edge technology that allows for the direct analysis of rRNA molecules, complete with all their chemical modifications. 

This method provides a significant advantage over traditional sequencing techniques, which often strip away these modifications during processing. 

“It allows us to see the modifications as they are, in their natural context,” Novoa noted.

Nanopore sequencing devices are small enough to fit in the palm of a hand and can process RNA samples in real time. This portability and efficiency mean that researchers can analyze minimal amounts of tissue. 

The study demonstrated that scanning as few as 250 RNA molecules was sufficient to differentiate between healthy and cancerous cells. 

“It is feasible to develop a rapid, highly accurate test that looks for cancer’s ribosomal fingerprint using minimal amounts of tissue,” Novoa added.

Turning cellular junk into a gold mine

Before the advent of nanopore sequencing, ribosomal RNA was often discarded as redundant information during research experiments. However, this study has transformed what was once overlooked into a treasure trove of diagnostic potential. 

“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,” Novoa explained.

The ability to analyze rRNA modifications in their natural state opens up new possibilities for understanding cellular processes and detecting disease.

The future of non-invasive cancer detection

In the long term, the researchers aim to develop diagnostic methods capable of detecting cancer’s ribosomal fingerprints through circulating RNA in blood samples. 

This approach would eliminate the need for invasive tissue biopsies, making the process more accessible and less painful for patients.

The researchers caution, however, that more work is needed before the technology can be applied in clinical settings. “We’re just scratching the surface,” Milenkovic says. “We need larger studies to validate these biomarkers across diverse populations and cancer types.”

Future directions in cancer research

One of the most intriguing questions raised by the study is why rRNA modifications change in cancer cells. Understanding whether these changes drive cancer progression could lead to innovative therapies aimed at reversing harmful modifications. 

By identifying the mechanisms responsible for adding or removing these chemical marks, researchers hope to uncover new ways to combat cancer at its molecular roots.

“We are slowly but surely unravelling this complexity,” Novoa said. “It’s only a matter of time before we can start understanding the language of the cell.”

A new horizon for early cancer detection

This pioneering work lays the foundation for transformative diagnostic tools that could revolutionize cancer detection and treatment. 

By leveraging ribosomal fingerprints and the power of nanopore sequencing, researchers are opening new doors to earlier, faster, and more accurate cancer diagnoses. 

The potential to save lives through timely intervention underscores the importance of this breakthrough in the fight against cancer.

Image Credit: Queralt Tolosa/Centro de Regulación Genómica

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