Studies could lead to new prognostic biomarkers and clinical laboratory diagnostics for cancer
Might fungi be involved in human cancers? Two separately published studies have found fungal DNA in various cancers in the human body. However, the researchers are unclear on how the fungi got into the cancer cells and if it is affecting the cancers’ pathology. Nevertheless, these discoveries could lead to utilizing tumor-associated fungal DNA as clinical laboratory diagnostics or prognostic biomarkers in the fight against cancer.
“The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens,’” said Ravid Straussman, MD, PhD (above), a principal investigator at Weizmann Institute of Science and one of the authors of the study in a UCSD press release. These findings could lead to new clinical laboratory diagnostics and prognostic biomarkers. (Photo copyright: Weizmann Institute of Science.)
.
Microbiome Key to Cancer Biology and Detection
To perform their research, the team examined 17,401 samples of patient tissues, blood, and plasma across 35 different types of cancers in four independent cohorts. They discovered fungal DNA and cells in low abundances in many human cancers.
“The existence of fungi in most human cancers is both a surprise and to be expected,” said biologist Rob Knight, PhD, founding Director of the Center for Microbiome Innovation and Professor of Pediatrics and Computer Science and Engineering at UC San Diego in a UCSD press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.”
The main highlights of this study include:
Fungi detected in the different cancer types were often intracellular.
Multiple fungal-bacterial-immune ecologies were detected across tumors.
Intratumoral fungi stratified clinical outcomes, including immunotherapy response.
Cell-free fungal DNA found in both healthy and cancer patients in early-stage disease.
Fungi found on the human body appear as either environmental fungi, such as yeasts and molds, and commensal fungi, which live either on or inside the body. Both are typically harmless to most healthy people and can provide some benefits, such as improving gut health, but they may also be a contributing factor in some disease.
The researchers found that there were notable parallels between specific fungi and certain factors, such as age, tumor subtypes, smoking status, immunotherapy responses, and survival measures.
“These findings validate the view that the microbiome in its entirety is a key piece of cancer biology and may present significant translational opportunities, not only in cancer detection, but also in other biotech applications related to drug development, cancer evolution, minimal residual disease, relapse, and companion diagnostics,” said Gregory Sepich-Poore, MD, PhD, one of the study’s authors and co-founder and chief analytics officer at biotechnology company Micronoma, in the UCSD press release.
New Clinical Laboratory Tests to Identify Fungal Species in Cancer
Researchers from Duke University and Cornell University uncovered compelling evidence of fungi in multiple cancer types and focused on a detected link between Candida and gastrointestinal cancers.
They found that “several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival,” according to their paper.
Their analysis of multiple body sites revealed tumor-associated mycobiomes in fungal cells. The researchers found that fungal spores known as blastomyces were associated with tumor tissues in lung cancers, and that high rates of Candida were present in stomach and colon cancers.
The Duke/Cornell researchers hope their work can provide a framework to develop new tests that can distinguish fungal species in tumors and predict cancer progression and help medical professionals and patients chose the best treatment therapies.
“These findings open up a lot of exciting research directions, from the development of diagnostics and treatments to studies of the detailed biological mechanisms of fungal relationships to cancers,” said Iliyan Iliev, PhD, Associate Professor of Microbiology and Immunology in Medicine, Weill Cornell Medicine, and one of the authors of the study, in a Weill news release.
More research is needed to determine if fungal DNA plays a role in disease pathology or if its presence does not have any causal link.
“It’s plausible that some of these fungi are promoting tumor progression and metastasis, but even if they aren’t, they could be very valuable as prognostic indicators,” Iliev said.
The insights gleaned from these two studies will be of particular interest to microbiologists, clinical laboratory professionals, and anatomic pathologists. Additional research could answer questions about how and if fungi infect tumors and if such fungi is a factor that increases cancer risk and outcomes.
Genetic data captured by this new technology could lead to a new understanding of how different types of cells exchange information and would be a boon to anatomic pathology research worldwide
What if it were possible to map the interior of cells and view their genetic sequences using chemicals instead of light? Might that spark an entirely new way of studying human physiology? That’s what researchers at the Massachusetts Institute of Technology (MIT) believe. They have developed a new approach to visualizing cells and tissues that could enable the development of entirely new anatomic pathology tests that target a broad range of cancers and diseases.
Scientists at MIT’s Broad Institute and McGovern Institute for Brain Research developed this new technique, which they call DNA Microscopy. They published their findings in Cell, titled, “DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction.”
Joshua Weinstein, PhD, a postdoctoral associate at the Broad Institute and first author of the study, said in a news release that DNA microscopy “is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen. It will allow us to see how genetically unique cells—those comprising the immune system, cancer, or the gut for instance—interact with one another and give rise to complex multicellular life.”
The news release goes on to state that the new technology “shows
how biomolecules such as DNA and RNA are organized in cells and tissues,
revealing spatial and molecular information that is not easily accessible
through other microscopy methods. DNA microscopy also does not require
specialized equipment, enabling large numbers of samples to be processed
simultaneously.”
The images above, taken from the MIT study, compares optical imaging of a cell population (left) with an inferred visualization of the same cell population based on the information provided by DNA microscopy (right). Scale bar = 100 μm (100 micrometers). This technology has the potential to be useful for anatomic pathologists at some future date. (Photo and caption copyrights: Joshua Weinstein, PhD, et al/Cell.)
New Way to Visualize Cells
The MIT researchers saw an opportunity for DNA microscopy to
find genomic-level cell information. They claim that DNA microscopy images
cells from the inside and enables the capture of more data than with
traditional light microscopy. Their new technique is a chemical-encoded
approach to mapping cells that derives critical genetic insights from the
organization of the DNA and RNA in cells and tissue.
And that type of genetic information could lead to new precision medicine treatments for chronic disease. New Atlas notes that “ Speeding the development of immunotherapy treatments by identifying the immune cells best suited to target a particular cancer cell is but one of the many potential application for DNA microscopy.”
In their published study, the scientists note that “Despite enormous progress in molecular profiling of cellular constituents, spatially mapping [cells] remains a disjointed and specialized machinery-intensive process, relying on either light microscopy or direct physical registration. Here, we demonstrate DNA microscopy, a distinct imaging modality for scalable, optics-free mapping of relative biomolecule positions.”
How DNA Microscopy Works
The New York Times (NYT) notes that the advantage of DNA microscopy is “that it combines spatial details with scientists’ growing interest in—and ability to measure—precise genomic sequences, much as Google Street View integrates restaurant names and reviews into outlines of city blocks.”
And Singularity Hub notes that “ DNA microscopy, uses only a pipette and some liquid reagents. Rather than monitoring photons, here the team relies on ‘bar codes’ that chemically tag onto biomolecules. Like cell phone towers, the tags amplify, broadcasting their signals outward. An algorithm can then piece together the captured location data and transform those GPS-like digits into rainbow-colored photos. The results are absolutely breathtaking. Cells shine like stars in a nebula, each pseudo-colored according to their genomic profiles.”
“We’ve used DNA in a way that’s mathematically similar to photons in light microscopy,” Weinstein said in the Broad Institute news release. “This allows us to visualize biology as cells see it and not as the human eye does.”
In their study, researchers used DNA microscopy to tag RNA
molecules and map locations of individual human cancer cells. Their method is
“surprisingly simple” New Atlas reported. Here’s how it’s done,
according to the MIT news release:
Small synthetic DNA tags (dubbed “barcodes” by the MIT team) are added to biological samples;
The “tags” latch onto molecules of genetic material in the cells;
The tags are then replicated through a chemical reaction;
The tags combine and create more unique DNA labels;
The scientists use a DNA sequencer to decode and reconstruct the biomolecules;
A computer algorithm decodes the data and converts it to images displaying the biomolecules’ positions within the cells.
The visualization above was created from data gathered by DNA microscopy, which peers inside individual cells. It demonstrates how DNA microscopy enables scientists to identify different cells (colored dots) within a sample—with no prior knowledge of what the sample looks like. (Photo and caption copyright: Joshua Weinstein, PhD, et al./Cell.)
“The first time I saw a DNA microscopy image, it blew me away,” said Aviv Regev, PhD, a biologist at the Broad Institute, a Howard Hughes Medical Institute (HHMI) Investigator, and co-author of the MIT study, in an HHMI news release. “It’s an entirely new category of microscopy. It’s not just a technique; it’s a way of doing things that we haven’t ever considered doing before.”
Precision Medicine Potential
“Every cell has a unique make-up of DNA letters or genotype. By capturing information directly from the molecules being studied, DNA microscopy opens up a new way of connecting genotype to phenotype,” said Feng Zhang, PhD, MIT Neuroscience Professor,
Core Institute Member of the Broad Institute, and
Investigator at the McGovern Institute for Brain Research at MIT, in the HHMI
news release.
In other words, DNA microscopy could someday have applications in precision medicine. The MIT researchers, according to Stat, plan to expand the technology further to include immune cells that target cancer.
The Broad Institute has applied for a patent on DNA
microscopy. Clinical laboratory and anatomic pathology group leaders seeking
novel resources for diagnosis and treatment of cancer may want to follow the MIT
scientists’ progress.
Pole-to-pole sampling of marine life leads researchers to conclude the world’s oceans could hold the key to many scientific and biotechnological advancements
Virologists and microbiologists will be intrigued to learn that scientists at Ohio State University (OSU) have identified nearly 200,000 previously unknown viruses living deep in the oceans. The catalog of 195,728 viruses could serve as a “road map” to a better understanding of ecosystems within the world’s oceans and the role they play in maintaining the health of the planet.
Though the research was not specifically directed at developing useful insights for clinical care, it could one day lead to new diagnostic assays or therapies. For clinical laboratories and anatomic pathology groups, this study demonstrates how understanding and knowledge about viruses and other organisms continue to grow.
The researches published their findings in the journal Cell.
Viruses Are Tiny but Important
The OSU researchers led a 24-member team’s effort to expand
the catalog of ocean viruses and draw the first global map of viral diversity.
“Viruses tend to steal genes and do really interesting
things with them. So, someone who’s savvy in biotechnology can mine this data
set to find new enzymes that can help us in our everyday lives, whether that’s
cosmetic products or creating a new thermocycler or some sort of engineering
process,” Matthew
Sullivan, PhD, a microbiologist at OSU and one of the study’s authors, told
CNN.
“Viruses are these tiny things that you can’t even see, but because they’re present in such huge numbers, they really matter,” Matthew Sullivan, PhD, a microbiologist at Ohio State University and one of the study’s authors, said in a new release. “We’ve developed a distribution map that is foundational for anyone who wants to study how viruses manipulate the ecosystem. There were many things that surprised us about our findings.” These new discoveries could someday form the basis for new medical laboratory tests and therapeutic drugs. (Photo copyright: Ohio State University.)
According to the news release, “The samples were collected during the unprecedented three-year Tara Oceans Expedition, in which a team of more than 200 experts took to the sea to catalog and better understand the unseen inhabitants of the ocean, from tiny animals to viruses and bacteria.”
“What was really exciting was now being able to study these viruses at two important levels—the population level and by looking at genetic variation within each population, which tells us about evolution,” Ann Gregory, PhD, co-lead author of the study, said in an OSU news release. “We have expanded the number of known viral populations more than tenfold and this new map will help us understand the impact of ocean viruses on a global level,” she added.
A news release from Tara Ocean Foundation notes that prior ocean surveys had identified 16,000 viral species.
Massive Quest for Knowledge
The OSU scientists studied ocean life from varying ocean depths, stretching from pole to pole, using samples collected during the Tara Oceans expeditions, which took place from 2009-2013. The Tara Ocean Foundation has backed 11 scientific expeditions and collected more than 60,000 samples that have been the basis for more than 70 scientific publications.
The team of researchers split the viruses into five
ecological zones: all depths of the Arctic and Antarctic and three distinct
depths of the Temperate and Tropical regions, noted the OSU study.
By developing new methods to sequence viruses in planktonic
populations, the OSU research team, according to the Tara Ocean press release,
was able to understand genetic variations:
Between individuals within each population;
Between populations within each viral community;
and
Between communities across several environments
of the global oceans, as well as study the driving forces behind all these
variations.
In its news release, Tara Ocean Foundation pointed out one
surprise was the “cradle of viral diversity” found in the Arctic Ocean, which
had not been part of earlier studies of ocean life.
“This research has significant implications for
understanding how ocean micro-organisms affect the atmosphere,” Sullivan said
in the Cell Press news release, which goes on to note that, “The investigators
say that having a more complete picture of marine viral distribution and
abundance will help them to determine which viruses they should be focusing on
for further studies.”
“Previous ocean ecosystem models have commonly ignored
microbes, and rarely included viruses, but we now know they are a vital
component to include,” said Sullivan.
At this time, the OSU study offers little that clinical
laboratories can use other than a deeper awareness of how viruses impact our
world and environment. However, further study of the ocean depths may yield
surprises that also expand medical knowledge and lead to new therapies and
diagnostic tests.
Wyss Institute develops prototype Ebola test in less than 12 hours with $20 in materials, perhaps paving the way for inexpensive paper-based diagnostic tests with a wide range of applications outside the medical laboratory
One goal of many synthetic biology researchers is to create in vitro diagnostic testing systems that produce results that are as accurate as those produced in today’s state-of-the-art clinical laboratories, yet are much cheaper to run because they incorporate low-cost materials, such as paper.
Recently, two teams of researchers worked to demonstrate how several synthetic biology methods, when combined with programmable paper-based diagnostic platform, could detect antibiotic-resistant bacteria and strain-specific Ebola virus. These findings were published in a peer-reviewed medical journal last fall.
Such cell-free circuits embedded in paper could be the breakthrough in synthetic biology that leads to pocketsize blotter tests that can detect such diseases as Ebola in the field. Should this line of research be applied to clinical settings, pathologists and medical laboratory scientists could soon be processing bandages that change colors in the presence of certain bacteria, or examining paper-based clothing infused with diagnostic laboratory tests that react to bio-markers specific to a chronic disease patient’s condition. (more…)
Additional studies are needed before medical laboratory tests for ‘lean’ microbes can be developed for use by physicians treating overweight and obese patients
Researchers at Cornell University have identified a family of microbes that may provide a genetic explanation for why some people are able to stay thin. If their findings are validated, a clinical laboratory test for these bacteria, and a macrobotic regiment to help people lose weight or stay lean, could be down the road.
Ruth Ley, Ph.D., is a Cornell University Associate Professor of Microbiology, and the research paper’s senior author. She believes the new Cornell study makes clear the connection between the human genotype and health-associated gut bacteria. (more…)
