MiRNA expression in plasma extracellular vesicles of prostate cancer patients after radical prostatectomy

Prostate cancer (PCa) is a common cancer in men, requiring accurate diagnosis and monitoring of treatment efficacy for in time revealing and eliminating cancer relapse. Radical prostatectomy is the most common treatment for prostate cancer. However, in 20%–40% of patients after surgery, PSA blood tests show a so-called “biochemical recurrence” of the disease, at that only 30% of these patients experience actual cancer progression. The trend towards personalized medicine induces looking for novel diagnostic/prognostic markers, including molecular biological ones. Methods for monitoring the effectiveness of PCa therapy must be inexpensive, reproducible and easily accessible to patients in order to allow continuous tracking of the patient's health before and after treatment. The most easily accessible biomaterial for monitoring the cancer process is the biological fluids of patients, namely blood and urine.

Human biological fluids contain about 3000 different small molecules (18 to 25 nucleotides long) classified as microRNA. Some of them were found to be related to tumor process and thus, could be used for tumor diagnostics/monitoring.

“In our laboratory, under the direction of Dr. Pavel Laktionov, work is being carried out to study cell-free microRNAs in the blood and urine during the development of various oncological diseases,” says Olga Bryzgunova, co-author of the study who began the project and is currently a PhD at the Institute of Chemical Biology and Fundamental Medicine.

Changes in microRNA concentrations and ratios are observed during the development of many diseases, including oncological ones, such as prostate cancer.

“Ideally, as a patient is treated and recovering, all microRNA levels should tend toward "healthy" levels,” says Olga Bryzgunova.

Despite the underlying assumption and large-scale studies conducted both in Russia and around the world for many years single/unique diagnostic or/and prognostic microRNAs which are able to predict prostate cancer or cancer therapy efficacy were not found yet. It obviously happened due to functional features of microRNAs. They affect the work of many important genes, but act on the principle: one gene can be influenced by many microRNAs and one microRNA can influence dozens of genes.

Our study showed that it is necessary to analyze combinations of microRNAs, namely, to monitor multiple changes of diagnostic microRNA pairs, and it is necessary to consider mutual changes not in one pair, but in several pairs of microRNAs simultaneously.

The researchers made the discovery by analyzing changes in 72 pairs of microRNAs (consisting of 14 different microRNAs) in the blood extracellular vesicles of patients with prostate cancer before treatment and after surgery and comparing the data with two control groups: healthy donors and patients with a benign disease (benign hyperplasia) of the prostate. It was shown significant changes of 11 miRNA ratios (from 72 pair ratios studied) changed after radical prostatectomy. Moreover, the most significant microRNAs (miR-125b and miR-30e) were identified: one of two miRNAs took part in each miRNA ratio whose relative expression changed after surgery.

An advantage of the technology offered is the lack of correlation between microRNA data and other biochemical markers, which suggests the possible use of the microRNA test as an independent and stand-alone test.

However, since blood is a biological fluid that washes all the organs and tissues of the body, it also contains a “molecular trace” from all of them. Our laboratory is also working on studying pairwise changes in microRNA in urine in prostate diseases. As we assumed, urine is not only a more convenient source in terms of taking biomaterial, but also a more meaningful liquid in terms of the presence of prostate disease tumor markers, since prostate gland secretion gets directly into the urine.

The results of our long-term studies not only confirm the diagnostic and prognostic potential of such micromolecules as microRNA in various biological fluids, but also take personalized medicine methods to a new level, capable of leading to more accurate prognoses and timely adjusted treatment, and therefore to a faster patient recovery after therapy.

This paper was published in ExRNA. Bryzgunova O, Yakovlev A, Ostaltsev I, Laktionov P, Konoshenko M. MiRNA expression in plasma extracellular vesicles of prostate cancer patients after radical prostatectomy. ExRNA 2024(3):0014. https://doi.og/10.55092/exrna20240014