Bacterial DNA signatures in blood point to new universal cancer test
Developing a simple blood test that can detect all kinds of early-stage cancers is something of a holy grail for many researchers. A huge variety of different blood-based cancer diagnostic methods are currently in development tracking everything from protein biomarkers to circulating tumor DNA. Now a new study led by researchers from UC San Diego is suggesting unique microbial DNA signatures can be detected in blood samples that can not only identify dozens of different cancers but also catch the disease in its earliest stages.
“Almost all previous cancer research efforts have assumed tumors are sterile environments, and ignored the complex interplay human cancer cells may have with the bacteria, viruses and other microbes that live in and on our bodies,” explains Rob Knight, director of the Center for Microbiome Innovation at UC San Diego. “The number of microbial genes in our bodies vastly outnumbers the number of human genes, so it shouldn’t be surprising that they give us important clues to our health.”
The genesis of the new study came in 2017 when medical student Gregory Poore became intrigued by the growing volume of research finding links between bacteria and cancer. As well as discovering associations between gut bacteria and cancer treatment efficacy, a number of recent studies have uncovered novel links between particular cancers and specific bacteria.
The first stage of the new research was to closely examine thousands of human tumor samples to determine the presence of microbial DNA. Using data from The Cancer Genome Atlas, the researchers analyzed over 18,000 tumor samples, spanning 33 different types of cancer. Machine learning models were then trained to dig through the mass of data and determine unique microbial DNA signatures that could be linked to specific cancer types.
Not only were these models initially successful in detecting cancer types from microbial DNA signatures, but the results held strong even after the researchers eliminated stage III and IV cancers from the dataset. This suggests the microbial patterns are present in blood at the earliest stages of the disease.
The final stage of the preliminary study was testing these microbial signatures in real-life conditions. A number of plasma samples were taken from prostate, lung and skin cancer patients. All the patients were suffering from stage III or higher cancers, and the cohort included a control group of plasma samples taken from cancer-free subjects.
For what is essentially a proof-of-concept study, the results were impressive. The models were able to correctly diagnose 86 percent of lung cancer patients. And just as importantly, the model reported no false positive lung cancers in the healthy control group. The model also revealed 81 percent accuracy in distinguishing prostate cancer from lung cancer, affirming the specificity of each microbial DNA signature.
“The ability, in a single tube of blood, to have a comprehensive profile of the tumor’s DNA (nature) as well as the DNA of the patient’s microbiota (nurture), so to speak, is an important step forward in better understanding host-environment interactions in cancer,” says Sandip Pravin Patel, a co-author on the new study.
It is very early days for this research and a huge amount of work is needed before this kind of diagnostic test moves to clinical uses. Plus, the research raises a number of questions around how these microbes are linked with specific types of cancer. It is unclear at this stage exactly where these microbes are located and how they may be interacting with individual tumors.
“Poore et al. and others identified microbial signatures in tumors on the basis of nucleic-acid sequences; however it is not known where these microbes are located (within or around tumor cells, immune cells or in connective tissue known as the stroma) and whether or not they are alive,” write a pair of University of Texas researchers not affiliated with the research in an editorial accompanying the new study. “And more work will be needed to determine whether the microbes are driving cancer or are merely passengers in an altered tumor microenvironment.”
Sandrine Miller-Montgomery, a co-author on the new research, recognizes these novel questions and suggests the study is only the beginning of investigations into how the blood microbiome interacts with cancer. As well as introducing a possible new diagnostic tool, Miller-Montgomery suggests the discovery of these microbial signatures may lead to novel treatments.
“This new understanding of the way microbial populations shift with cancer could open a completely new therapeutic avenue,” says Miller-Montgomery. “We now know the microbes are there, but what are they doing? And could we manipulate or mimic these microbes to treat cancer?”
The new research was published in the journal Nature.
Source: UC San Diego