Tag: biomarkers

Less than Half of Community Oncologists Use Biomarker Testing

Photo by Robina Weermeijer on Unsplash

A survey found that less than half of community oncologists surveyed indicated using biomarker testing to guide patient discussions, compared to 73% of academic clinicians.

Recent advances have substantially altered the management of lung cancer but, there is a concern these new methods, which include biomarker testing, will not be used equally throughout the health care system and worsen disparities that may already be entrenched.

To determine this, the Association of Community Cancer Centers (ACCC), led by Leigh Boehmer, Pharm.D., chief medical officer, developed a US oncology clinician-facing survey instrument.

To help guide clinicians in the use of biomarker testing, the College of American Pathologists, the IASLC, and the Association for Molecular Pathology published the 2018 CAP/IASLC/AMP Molecular Testing Guidelines for Lung Cancer. Dr. Boehmer reported that of the 99 responses collected, only 40 percent indicated they were “very” or “extremely familiar” with the 2018 Guidelines.

The researchers found that clinicians were most confident in selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, but less confident in determining when to order testing and coordination of care. This lack of communication was echoed in focus groups, Dr Boehmer reported.

Clinicians are most likely to order biomarker testing to make more accurate treatment decisions and inform patient discussions, but only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions compared to 73% of academic clinicians.

Asked about preferences when making a final testing decision, 41% of clinicians prefer that they share responsibility with the patient while 52% prefer to make the final decision themselves. Only 6% prefer that the patient make the final decision. Focus groups suggested that clinicians perceive that patients rarely understand what testing entails and how it affects treatment options.

To make more informed decisions about biomarker testing, clinicians indicated that they need more information on financial resources, as well as education around both published guidelines and practical implications of clinical data. Sixty-seven percent of clinicians provide printed educational materials to their patients. When asked what resources their patients need most, 27% said their patients need handouts or educational resources, followed by psychosocial support (23%) and financial assistance (22%).

“This study identifies key areas of ongoing clinician need related to biomarker testing, including increased guideline familiarity, practical applications of guideline-concordant testing, and how to optimally help coordinate multidisciplinary care,” said Dr. Leigh Boehmer, Pharm.D. “Professional organisations and advocacy groups should focus on developing impactful education materials and tools for improving patient-clinician discussions about biomarker testing.”

Source: International Association for the Study of Lung Cancer

Study Uncovers Assortment of New Biomarkers for Dementia

Source: National Cancer Institute on Unsplash

An international study identified 15 novel biomarkers that are linked to late-onset dementias. These protein biomarkers predict cognitive decline and subsequent increased risk of dementia 20 years before the disease onset. 

The proteins identified by the study are involved with immune system dysfunction, blood-brain-barrier dysfunction, vascular pathologies, and central insulin resistance. Six of these proteins can be modified with currently available medications.  

“These findings provide novel avenues for further studies to examine whether drugs targeting these proteins could prevent or delay the development of dementia,” explained lead author Joni Lindbohm MD, PhD from the University College London and University of Helsinki.

The study findings have been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Pathophysiological research on dementia aetiology has focused on amyloid beta and tau proteins, but thus far prevention and treatment trials targeting these biomarkers have been unsuccessful. This has spurred the search for other potential mechanisms that could predispose to dementia. Recent development of scalable platforms has made it possible to analyse a wide range of circulating proteins, which may reveal novel dementia-linked biological processes.

In this study, the researchers analysed proteins with a novel large-scale protein panel from stored blood samples of the British Whitehall II and US Atherosclerosis Risk in Communities (ARIC) study collected 20 years ago. Using a panel of 5000 proteins, the researchers identified proteins in plasma that predicted cognitive decline in 5-yearly screenings and subsequent onset of clinical dementia. The 15 proteins that were identified were predictive of dementia in both the British and US cohorts.

“This new study is the first step in our 5-year Wellcome Trust funded research programme. We will next examine whether the identified proteins have a causal association with dementia, and whether they are likely to be modifiable, and druggable”, said study author Professor Mika Kivimäki, Director of the Whitehall II study at University College London.

The research programme ultimately aims to identify novel drug targets for dementia prevention.

Source: EurekAlert!

Researchers Hit upon a Possible Biomarker for Schizophrenia

Investigators at Sanford Burnham Prebys have discovered that a certain protein circulating in blood could be a potential biomarker for schizophrenia. The activity of this protein, present in both the brain and blood, affects neural connections in human brains and is uniquely imbalanced in people with schizophrenia. 

The study, an international collaboration among groups at Yokohama City University Graduate School of Medicine in Japan and the Department of Psychiatry at Harvard Medical School in Belmont, Massachusetts, was recently published in PNAS.

“This study examined the activity of CRMP2, a protein found in the brain (called a ‘cytoskeletal protein’) that regulates how neurons make connections with each other,” said co-senior author of the study Evan Y Snyder, MD, PhD, director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys. “CRMP2 also happens to be expressed in lymphocytes in the blood and can therefore be readily sampled in people by doing nothing more than a simple venipuncture.

“There was an abundance of CRMP2 levels in samples from people with schizophrenia compared to people without the disorder. We also saw structural abnormalities in the dendrites of neurons that could potentially be disabling because dendrites play an important role in receiving impulses from other nerve cells in the brain.”

In previous research, most people were found to maintain an even proportion of the two forms of CRMP2: its active, non-phosphorylated form and its inactive, phosphorylated form. Postmortem brain tissue and then blood samples from people with schizophrenia were examined and compared these levels to those in people without the disorder.

The findings indicated that the amount of active CRMP2 was too high in people with schizophrenia and, at least in young people with schizophrenia, was not balanced by an appropriate amount of increased inactive CRMP2. That imbalance between active and inactive CRMP2 could account for some dysfunctions in neural connections.

Testing blood for high levels of active CRMP2, along with low levels of inactive CRMP2, could support schizophrenia diagnosis.

“Schizophrenia can be challenging to diagnose early on or in young patients for a number of reasons,” explained Dr Snyder. “Pairing a blood test with psychiatric and neurobehavioral exams could help doctors distinguish schizophrenia from other conditions that have somewhat similar symptomologies, such as the manic phase of bipolar disorder or other behavioral, personality, or thought disorders.

“Our results were most striking in people under the age of 40, and even more so in people under the age of 30. An early diagnosis could improve the clinical management of affected individuals as well as accelerate the development of new therapeutic options,” Dr Snyder added.

As a next step, the researchers want to delve into the molecular biology of the disease to discover the ‘regulator’  that balances most people’s CRMP2 levels. They also want to conduct a larger, multi-centre clinical study that compares schizophrenia with other psychiatric disorders, which would include participants from more ethnicities and age groups.

Source: Sanford Burnham Prebys Medical Discovery Institute

Journal information: Munetaka Nomoto el al., “Clinical evidence that a dysregulated neural network modulator may aid in diagnosing schizophrenia,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2100032118

New Biomarker for Soft Tissue Infections

This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Photo by CDC on Unsplash
This illustration depicted a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Image by CDC on Unsplash

Researchers have identified a new and very promising biomarker for bacterial soft tissue infections, which previously lacked one. 

In bacterial soft tissue infections, rapid diagnosis is crucial in reducing the risk of severe injury or amputation. Vague symptoms and a varied patient presentations increase the risk of misdiagnosis.The study, by  Researchers at Karolinska Institutet in Sweden  and other research institutions, and published in the Journal of Clinical Investigation, may have implications for both diagnosis and treatment.

Last author Anna Norrby-Teglund, Professor, Department of Medicine, Karolinska Institutet, said: “There are currently no tools for safe, rapid diagnosis in life-threatening soft tissue infections. Our findings are consequently very interesting as the biomarkers identified are possible candidates for improved diagnostics. The results are also relevant for individualised treatment in the future.”

Necrotising soft tissue infections (NSTI) are bacterial infections which are characterised by rapid tissue degradation. Such infections, often caused by streptococci, while relatively uncommon, are extremely serious. In most cases they necessitate intensive care and can quickly become life-threatening.

Extensive surgery, intravenous antibiotics are often required to prevent the infection from spreading, and amputation may be required in extreme situations. Many patients also develop sepsis, which further complicates the course of the condition.

Early, correct diagnosis is crucial to save lives and avoid amputation, but this is complicated by factors such as vague symptoms including vomiting, fever and severe pain, as well as the heterogeneous group of patients. Despite recommendations for surgical evaluation in suspected NSTI, there is a considerable risk of misdiagnosis.

Currently, various laboratory tests, including white blood cell counts, are used as diagnostic tools, but suffer from low sensitivity. NSTI-specific biomarkers are therefore needed. The condition is classified into four types depending on the infecting organism.

Researchers at Karolinska Institutet, Haukeland University Hospital, Norway, and Copenhagen University Hospital, Denmark, have now been able to identify biomarkers specific to different patient groups with soft tissue infections.

Using machine learning, the researchers analysed 36 soluble factors in blood plasma from the 311 NSTI patients included in the international INFECT study. Control groups included patients with suspected NSTI and sepsis, respectively.

The analyses showed a new biomarker that accurately identifies patients with tissue necrosis.

“The new biomarker, thrombomodulin, proved to be superior to the laboratory parameters used clinically today. The analyses also identified biomarkers for patients with soft tissue infection caused by different types of bacteria, as well as patients who developed septic shock,” said first author Laura Palma Medina, researcher at the Department of Medicine, Karolinska Institutet (Huddinge).

Source: Karolinska Institutet

Journal information: Palma Medina, L.M., et al. (2021) Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections. Journal of Clinical Investigation. doi.org/10.1172/JCI149523.

T-Cells Could Identify ‘The Bends’ in Divers

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A new study investigated genetic changes that occur in a serious condition affecting scuba divers — ‘the bends’ — and found that inflammatory genes and white blood cell activity are upregulated. The findings could lead to biomarkers that will help doctors to diagnose the condition more precisely.

The bends, more formally known as decompression sickness, is a potentially lethal condition that can affect divers. Symptoms include joint pain, a skin rash, and visual disturbances. In some patients, the condition can be severe, potentially leading to paralysis and death. The bends can also affect people working in submarines, flying in unpressurised aircraft or in spacewalks.

It has been studied for a long time: a 1908 paper correctly hypothesised that it involves bubbles of gas forming in the blood and tissue due to pressure decrease. Yet even after a century the precise mechanisms underlying the condition are not well understood. Animal studies have suggested that inflammatory processes may have a role in decompression sickness, but no-one had studied this in humans.

Nowadays, getting ‘the bends’ is rare as divers have well-established methods to mitigate risk, such as controlled ascents from the depths. Nevertheless, doctors have no means to test for the condition, if they do encounter it, and instead rely on observing symptoms and seeing whether patients respond to hyperbaric oxygen therapy.

To investigate decompression sickness, the researchers sampled the blood of divers who had been diagnosed with decompression sickness and also divers who had completed a dive without it. The blood samples were drawn at two times: within 8 hours of the divers emerging from the water, and 48 hours afterwards, when those divers with decompression sickness had undergone hyperbaric oxygen treatment. RNA sequencing analysis was done to measure gene expression changes in white blood cells.

“We showed that decompression sickness activates genes involved in white blood cell activity, inflammation and the generation of inflammatory proteins called cytokines,” explained Dr Nikolai Pace of the University of Malta, a researcher involved in the study. “Basically, decompression sickness activates some of the most primitive body defense mechanisms that are carried out by certain white blood cells.”

These genetic changes had diminished in samples from 48 hours after the dive, after the patients had been treated with hyperbaric oxygen therapy — an interesting finding. The results provide a first step towards a diagnostic test for decompression sickness, and may also reveal new treatment targets.

“We hope that our findings can aid the development of a blood-based biomarker test for human decompression sickness that can facilitate diagnosis or monitoring of treatment response,” said Prof Ingrid Eftedal of the Norwegian University of Science and Technology, who was also involved in the project. “This will require further evaluation and replication in larger groups of patients.”

Source: EurekaAlert!

Journal information: “Acute effects on the human peripheral blood transcriptome of decompression sickness secondary to scuba diving” Frontiers in Physiology, DOI: 10.3389/fphys.2021.660402

New Test Picks up Concussion Biomarkers in Saliva

A new test has been found to effectively pick up concussion biomarkers in the saliva of rugby players.

This paves the way for a non-invasive, easy-to-use pitch-side test to rapidly detect concussions for early treatment. Concussion is a serious problem in contact sports, with players such as college American Football athletes consistently underestimating its risk. Missing a concussion can have a range of consequences, from delayed recovery to more serious (albeit rare) injuries such as traumatic brain swelling.

Detecting concussions requires an assessment by a clinician of the signs and symptoms of the injury. However, recent advances in DNA sequencing technology have made it possible to use small non-coding RNAs (sncRNAs) as biomarkers in rapid tests. sncRNAs regulate the expression of different cellular proteins associated with various diseases, such as cancer and Alzheimer’s disease.

t is thought that since saliva can receive cellular signals directly from the cranial nerves in the mouth and throat, biomarkers from a brain injury would quickly show up.

A panel of 14 sncRNAs differentiated concussed players from those where traumatic brain injury had been suspected but ruled out, and from the comparison group, both straight after the game and 36–48 hours later.

Over two seasons, samples were collected before the rugby season began from 1028 players from the two elite professional tiers, and during standardised ‘gold standard’ head injury assessments at three time points—during the game, afterwards, and 36–48 hours later from 156 of these players .

The researchers also took saliva samples from a comparison group of 102 uninjured players, as well as 66 with muscle or joint injuries, and so had not had head injury assessments.

However, the researchers stressed that the observational study nature and design of this study cannot show that the biomarker test is any better than a gold standard clinical test for concussion.

“In community sport, [sncRNAs] may provide a non-invasive diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting,” while the test could be added to current head injury evaluation protocols at the elite level,” they add.

And as the biology of concussion is still not fully understood, sncRNAs might help to shed light on the response to injury as this evolves over time, they suggest.

“The detection of signatures of concussion at early time points in saliva (a non-invasively sampled biofluid) presents both at the pitch side, and in primary care and emergency medicine departments, an opportunity to develop a new and objective diagnostic tool for this common clinical presentation,” they conclude.

As an addendum to their findings, they added: “A patented salivary concussion test is in the process of being commercialized as an over-the-counter test for elite male athletes.

“Meanwhile our research team aims to collect further samples from players in two elite men’s rugby competitions to provide additional data to expand the test and develop its use. This will guide the prognosis and safe return to play after concussion and further establish how the test will work alongside the head injury assessment process.”

The researchers plan to add more participants to the SCRUM study, such as female athletes and community players.
Source: Medical Xpress

Journal information: Valentina Di Pietro et al. Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM), British Journal of Sports Medicine (2021). DOI: 10.1136/bjsports-2020-103274

New Biomarker Can Predict Response to Checkpoint Inhibitor Therapy

A team of researchers at Roswell Park Comprehensive Cancer Center have identified a biomarker that could be used to predict how well immune checkpoint inhibitors will be tolerated.

Immune checkpoint inhibitors (ICI) activate anti-tumour defences either through the disruption of inhibitory interactions between antigen-presenting cells and T cells at so-called checkpoints or else through the stimulation of activating checkpoints. Not all patients can tolerate ICI well; side effects can be severe, including colitis, which is one of the most common.

Pre-treatment biomarkers are of limited value in predicting response to ICI. Tumour biopsy shortly after ICI therapy is started can provide helpful information, but is invasive and difficult to do in some certain cancers.
Uncovering blood-based biomarkers that reflect the change of the tumour microenvironment and can predict a patient’s response to ICIs could improve current treatment regimens significantly, Dr. Ito notes. The team’s previous research indicates that T cells with varying levels of the chemokine receptor CX3CR1 responded differently to ICI therapy.

Based on those findings, the researchers sought to test CX3CR1 as a T cell biomarker in ICI therapy. They found that ICI therapy is linked to increased frequency and clonality of some CX3CR1-positive T cells; that the frequency of these CD8+ T cells stays high during ICI therapy; and that there are many genomic similarities between CD8+ tumour-infiltrating lymphocytes and this subset of CX3CR1-positive T cells.

Fumito Ito, MD, PhD, FACS, explained: “Although ICIs revolutionized the cancer treatment for significant numbers of people, many cancer patients do not respond to them, and some develop severe toxicity.”

“Currently, we are in need of a better biomarker to predict the response to immunotherapy, which is part of standard treatment in advanced and metastatic lung cancer,” said Hongbin Chen, MD, PhD. “This study sheds light on a promising blood-based biomarker that is potentially very useful in identifying which patients with lung cancer are most likely to benefit from immunotherapy. We look forward to investigating its utility in further clinical research.”

Source: News-Medical.Net

Journal information: Yamauchi, T., et al. (2021) T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors. Nature Communications.doi.org/10.1038/s41467-021-21619-0.

Plasma microRNAs as Biomarkers for Mild Brain Injury

Plasma microRNA could serve as biomarkers for the detection and diagnosis of mild traumatic brain injury, a recent study from the University of Eastern Finland (UEF) has found.

Mild traumatic brain injury is extremely difficult to detect as it is almost invisible to most imaging techniques, and visible signs in daily life may be masked by compensation for increased task difficulty.

Blood biomarkers can satisfy the demand for timely, accurate, easily accessible and affordable tests for mild traumatic brain injury. They are minimally invasive and can provide molecular information about the injury on an ongoing basis.

MicroRNAs (miRNAs) are non-coding sections of RNA that play a key role in gene expression. The researchers sequenced DNA in blood plasma taken from animal models subjected to mild and severe traumatic brain injury. They selected the miRNAs which showed the greatest potential for use as biomarkers for further analysis with polymerase chain reaction (PCR). They wanted biomarkers that were both sensitive and specific to traumatic brain injury in an animal model.

Dr Noora Puhakka, A. Virtanen Institute for Molecular Sciences, UEF, said, “We have been developing a suitable analysis and measurement method especially for miRNAs that can be found in small amounts in plasma, and this method is based on digital droplet PCR.

“Humans and animals share many identical miRNAs, and this makes them excellent candidates for translational studies, where results achieved in animal models are sought to be applied in humans. However, it has proven challenging to reproduce results from different studies and different sets of data. This is why assessing the quality of measurement methods, and reproducibility, is an extremely important part of biomarker research.”
The study a pair of possible biomarker candidates to diagnose mild traumatic brain injury both in the animal model and in human patients.  

“We found two interesting biomarkers in the animal model, the plasma miRNAs miR-9a-3p and miR-136-3p, which we then decided to analyse in blood samples taken from patients with traumatic brain injury. Elevated levels of these biomarkers allowed us to identify some of the patients who had experienced a mild traumatic brain injury,” Dr Puhakka explained.

“Both of these miRNAs are more abundant in the brain than in other tissues, and their elevated levels in plasma could possibly be due to brain injury and the level of its seriousness. However, further research in larger patient cohorts is still needed.”

Source: News-Medical.Net

Journal information: Gupta, S. D., et al. (2021) Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury. International Journal of Molecular Sciences. doi.org/10.3390/ijms22041563.