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Take a look at a selection of our recent media coverage:

Potential biomarker for depression and treatment response identified

6th January 2022

A potential biomarker indicating the presence of major depression and its response to antidepressant therapy could be diagnostically useful

A potential biomarker which indicates the presence of major depression and its response to treatment could become a useful diagnostic tool and create a platform for personalised medicine. This was the conclusion of a proof-of-concept study by a team led by researchers from Signant Health, Boston, USA.

Depression is the commonest mental illness worldwide and the incidence has increased by 49.8% from 1990 to 2017, affecting some 25.8 million people. Moreover, the incidence of major depression also appears to be on the increase, with a US study in 2021 indicating that number of US adults with major depression aged 18-34 years increased from 34.6 to 47.5% between 2010 and 2018. Although treatment of depression with antidepressant drugs has become widespread, some evidence from a real-world study suggests that only a third of patients achieve remission with the antidepressant, citalopram. A potential biomarker that not only identified those with major depression but also enabled tracking of a patient’s response to treatment could therefore be invaluable to clinicians.

Studies suggest that the cyclic adenosine monophosphate (cAMP) cascade is down regulated in major depression but up regulated by antidepressant treatment. Moreover, G protein coupled receptors and their attendant G proteins and effectors, such as adenylyl cyclase, are involved in the generation of cAMP. Many neurotransmitter receptors, G proteins, and signalling effectors such as second-messenger-generating enzymes are present in lipid rafts and one particular protein, G-s alpha (GSA), appears to be the target of antidepressants, which facilitate the activation of adenylyl cyclase by making GSA more available.

In the present study, researchers hypothesised that antidepressant treatment increases the concentration of GSA, enabling it to exit from the lipid raft and stimulating the enzyme, adenylyl cyclase. They used blood platelets to determine adenylyl cyclase activity based on its response to prostaglandin E1 (PGE1) stimulation, which served as their potential biomarker by measuring of the extent of GSA-adenylyl cyclase coupling in both patients with major depression and healthy controls. The level of depression was assessed using the Hamilton rating scale for depression (HamD) and included patients were required to have a score > 15 at the initial visit.

Findings

Using samples from 41 individuals with major depression and 44 healthy controls, baseline measurement revealed a significantly lower PGE1 activation in those with depression compared to controls (p = 0.02), suggesting that there was less GSA available. A total of 19 depressed individuals (6 men and 13 women) with a mean age of 50.6 years and a mean baseline HamD score of 20.4 consented to having a course of antidepressant therapy. After 6 weeks of treatment, there were 11 responders (HamD scores > 50% improvement from baseline) whose platelet samples demonstrated a significant increase in PGE1 stimulated adenylyl cyclase compared to non-responders (p = 0.05). In fact, treatment responders showed a 62% increase in mean PGE1 stimulation compared to baseline, compared to -4.6% decrease for non-responders.

The authors concluded that the translocation of GSA from lipid rafts, as reflected by an increased PGE1 stimulated adenylyl cyclase, after treatment with antidepressants, could be used as a potential biomarker for both major depression and patients response to therapy and called for future studies to determine the utility of this biomarker.

Citation

Targum SD et al. A novel peripheral biomarker for depression and antidepressant response Mol Psychiatry (2022).

Total bile acid concentration a possible biomarker for coronary artery disease

29th November 2021

The total bile acid concentration is lower in patients with visible coronary artery disease and could be an important disease biomarker

The total bile acid concentration among those with visible coronary artery disease (CAD) as seen with coronary angiography was approximately 50% lower than in patients without CAD, indicating that this might serve as an important biomarker for the disease. This was the finding of a study by researchers from the department of Cardiology, Cochin Hospital, Paris, France.

Cardiovascular disease is the leading cause of death globally, accounting for an estimated 17.9 million deaths every year. Moreover, other evidence shows that in patients with non-alcoholic fatty liver disease (NAFLD), who have an excessive fat deposition in the liver, there is a dysregulation of bile acid (BA) metabolism. Finally, one systematic review in 2013, revealed how NAFLD is a strong independent predictor of cardiovascular disease. Taken together, these findings might suggest that dysfunctional BA metabolism could be indicative of CAD.

For the present study, the French team sought to explore the relationship between total bile acid concentration and CAD by measuring the level of acids in patients referred for coronary angiography and who could well have CAD. In addition, the team also measured the concentration of 7-alpha C4, which serves as a marker for the production of bile acids by the liver to determine whether there was any correlation with CAD.

Findings

A total of 80 patients with a mean age of 61.5 years (61% male) were recruited, 45 who presented with significant CAD on angiography and the remainder who were normal. Both groups were comparable apart from the CAD group being significantly older (66 vs 57 years, p = 0.004), including more men (73% vs 49%, p = 0.02) and with a significantly higher diastolic pressure (77 vs 72 mmHg, p = 0.04).

After adjustment for age and gender, the total bile acid concentration was highly predictive of CAD, with an area under the curve of 83.6% (95% CI 74.5% – 92.8%) and an odds ratio, OR of 0.51 (95% CI 0.31 – 0.85, p = 0.01). In other words, bile acid levels were approximately 50% lower in patients with CAD. From a total of 28 different bile acids, the researchers identified that one particular BA, GCDCA acid, was also predictive of CAD (AUC = 83.6%) and with a similar odds ratio (OR = 0.60, 95% CI 0.01 – 0.51, p = 0.01). A further observation was how the levels of 7-alpha C4 was similar in both groups (0.13 vs 0.12 micromol/L). One interesting finding was how among 17 patients who had been prescribed statins, the mean concentration of total bile acid, doubled (0.68 to 1.37 micromol/L, p = 0.01) after one month of treatment.

In discussing these results, the authors suggested that the total bile acid concentration might serve as a natural braking mechanism and which protected against the development of atheromatous plaques. They concluded by proposing that GCDCA could serve as a biomarker and predictor of visible atheroma in patients with CAD.

Citation

Nguyen CC et al. Circulating bile acids concentration is predictive of coronary artery disease in human Sci Rep 2021

Keratin 17 as a potential biomarker for urothelial carcinoma

8th June 2021

Urothelial carcinoma is the most common cancer of the urinary tract and while urine cytology is used to screen for the cancer, it has a low sensitivity, promoting the need for a more specific marker.

Urothelial carcinoma (UC) or transitional cell carcinoma, is the most common form of bladder cancer and is the tenth most common cancer in the world. The urothelial cells that line the bladder and urinary tract are constantly exposed to environmental agents that are filtered through the kidneys and not surprisingly, 90% of bladder cancers arise in these cells. Detection of UC is based on subjective microscopic features that are not always able to distinguish between benign and low-grade UC. Now a team from Yale Cancer Centre, US have developed a urine screening test based on immunocytochemistry and detects keratin 17, a molecule that has been found to be over-expressed in a range of cancers such as those affecting the breast, ovaries and pancreas. The researchers wanted to examine whether identification of keratin 17 could be used to screen for UC and detect recurrent UC in urine samples.

The study involved two patient cohorts: one with haematuria and one with recurrent UC. In screening samples with haematuria, the test was found to have a sensitivity of 100% and specificity of 83%. In patients with recurrent UC, the corresponding specificity and sensitivities were 92% and 100%.

The test itself, URO17 is developed by KDx diagnostics and commenting on the results of the study, co-author, Dr Nam Kim, said “there is now a growing body of evidence that the non-invasive K17 urine test will make a significant positive impact on detection and management of UC”. The study authors concluded that the study provides evidence to support the development of prospective trials to further define the clinical and diagnostic impact of K17.

Source

Babu S et al. Keratin 17 Is a Novel Cytologic Biomarker for Urothelial Carcinoma Diagnosis. Am J Clin Pathol 2021