Scientists have reached a critical milestone in the study of liver cancer that lays the groundwork for predicting the illness's path, whether toward cure or recurrence. By analyzing the tissue in and around liver tumors, an international research team has identified a kind of genetic "fingerprint" that can help predict if patients' cancers will return.
The findings appear in the October 15 advance online edition of the New England Journal of Medicine and were made possible by a large-scale method for revealing genes' activity, which the researchers show can be applied to tissues that have been chemically preserved instead of frozen. This technical triumph promises to unlock biological information within millions of clinical samples previously intractable to genomic study.
"In most hospitals and clinics, the prevailing method of storing patient tissue involves a chemical fixative, which often precludes future genome-scale analyses. That means the vast majority of patient samples have effectively been off-limits to a variety of important questions," said senior author Todd Golub, who directs the Cancer Program at the Broad Institute of MIT and Harvard and is the Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute. "Our work reveals that it is indeed possible to access this biological trove, a step we hope will bolster future genomic discoveries throughout the scientific community."
Unlike many cancers, hepatocellular carcinoma, a form of liver cancer, is often detected early. That is because in the developed world, doctors can identify and closely monitor individuals at highest risk — those with a history of liver damage due to infection or chronic alcohol abuse, for example. Yet even with early diagnosis and treatment, the disease often recurs. And that development often proves fatal. The ability to pinpoint in advance those most at risk of suffering recurring cases could improve treatment, perhaps helping doctors choose more aggressive therapies for patients whose disease is most likely to return and identifying patients whose health should be carefully followed.
Genome-scale technologies are a powerful means to help develop such predictors, particularly methods that measure the activity (or "expression") of every human gene. However, a major obstacle to applying such methods to hepatocellular carcinoma, as well as other cancers, has been the technical requirements — samples must be frozen, not preserved, or "fixed," in the chemical formalin.
An international team of researchers from the Broad Institute, Harvard Medical School, Dana-Farber Cancer Institute, Mount Sinai School of Medicine, and elsewhere came together to develop an enhanced method for measuring gene expression in formalin-fixed tissues and applied it to samples from more than 300 liver cancer patients. Their work uncovered a striking pattern — a characteristic signature of more than 180 active and inactive genes linked with increased patient survival. Interestingly, this putative predictor was discovered not within the tumors per se, but within the normal tissue surrounding them.
In the future, the telltale gene signature could help distinguish patients whose tumors are likely to return. "Our findings underscore the potential of genomic signatures to help identify treatments that will be most beneficial to individual patients," said Golub, who is also an investigator at the Howard Hughes Medical Institute.
The discovery flows from an existing gene expression method that works on formalin-fixed tissues yet extracts information on just a few hundred genes. The researchers redesigned the technique to analyze roughly 6,000 genes — a subset that yields sufficient data to either directly measure or infer the expression levels of nearly all ~20,000 human genes.
Although further work is needed before the liver cancer findings can be used in the clinic, the current study marks a key step toward accelerating genomic discoveries with medical promise. Indeed, most patient tissue banks, especially those with valuable clinical data such as disease severity and course that are so vital to retrospective studies, are built from fixed samples and up until now have been largely inaccessible to genomic analysis. "In the Boston-area hospitals alone, we estimate that there are more than one million archived samples that can be analyzed with this approach," said Golub. "There's a wealth of information waiting to be explored."
Nicole Davis | EurekAlert!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences