Fast, uncomplicated, and specific: diagnosis of prostate cancer from blood samples
Early detection of prostate cancer, one of the most common types of
cancer in men, is often achieved with PSA tests. However, this blood
test for prostate-specific antigens gives many false positive results,
causing unnecessary biopsies and overtreatment. In the journal Angewandte Chemie, a Chinese research team now introduces a highly specific, non-invasive alternative to biopsy: the “thermophoretic AND gate operation” assay, abbreviated as Tango, quickly and reliably detects prostate cancer directly in blood samples.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
The Tango assay is based on the analysis of circulating extracellular
vesicles, which are membrane-bound “nanobubbles”. These come from all
cells of the body, circulate in the bloodstream, and contain numerous
biomarkers typical of the cells in which they originated. Isolation and
accumulation of the heterogeneous vesicles in complex samples requires
complex and expensive pre-treatments. The new method developed by a team
headed by Fei Tian, Bo Dai, and Jiashu Sun combines accumulation with a
logical AND gate operation in a single step for the identification of
the desired tumor vesicles.
The concentration process is based on thermophoresis, the movement of
particles based on a temperature gradient. The sample is placed into a
specially designed microchamber that is locally heated with an IR laser.
The vesicles preferentially move toward the heated spot. Polyethylene
glycol is also added to form a concentration gradient, which amplifies
the effect. This results in a 2800-fold accumulation around the laser
spot.
To identify the desired vesicles unequivocally and specifically, they
must contain two proteins that occur in high concentrations in prostate
tumors: prostate-specific antigen (PSMA) and epithelial cell-adhesion
molecule (EpCAM). The team introduced two probes based on aptamers,
which are short, single strands of DNA with a “programmed” 3-D structure
that specifically binds to a target molecule. In this case the two
targets are PSMA and EpCAM. Each of the probes has fluorescence dye.
In order to only detect vesicles that contain both tumor markers, the
team developed a logical AND operation. Both of the probes have a
little molecular “anchor” that specifically binds to the end of a DNA
connector. If both of the target proteins are found on a vesicle
membrane, both types of probe are linked by the DNA connector and the
two fluorescence dyes come close enough to each other for an energy
transfer. The one dye absorbs light and transfers part of the energy to
the other without radiation (Förster resonance energy transfer, FRET),
the second dye then emits light. The intensity of this FRET fluorescence
is a measure of the number of vesicles containing both tumor markers.
The Tango assay was able to identify patients with prostate cancer
out of a group with inconclusive PSA results with 91% accuracy in 15
minutes. It should also be possible to develop tango tests for other
types of cancer, according to the team from the National Center for
Nanoscience and Technology (Beijing) and Fudan University (Shanghai).
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About the Author
Dr. Jiashu Sun is a
professor at the National Center for Nanoscience and Technology (NCNST)
and University of the Chinese Academy of Sciences. Her main specialty is
developing innovative micro- and nanotechnologies for liquid biopsy.
She is also Director of Beijing Engineering Research Center for
BioNanotechnology.