ISSN 0006-2979, Biochemistry (Moscow), 2025, Vol. 90, No. 6, pp. 671-682 © Pleiades Publishing, Ltd., 2025.
Published in Russian in Biokhimiya, 2025, Vol. 90, No. 6, pp. 720-732.
671
Diagnostic and Prognostic Potential of Circulating
miR-1301-3p, miR-106a-5p, miR-129-5p, miR-3613-3p,
and miR-647 microRNAs in Gastric Cancer
Irina V. Bure
1,2,a
*, Ekaterina A. Vetchinkina
1
, Alexei I. Kalinkin
3
,
Ekaterina B. Kuznetsova
1,3
, Alevtina E. Kiseleva
1
, Ekaterina A. Alekseeva
1
,
Nikolay S. Esetov
1
, and Marina V. Nemtsova
1,3
1
I. M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
2
Russian Medical Academy of Continuous Professional Education, 125993 Moscow, Russia
3
Research Centre for Medical Genetics, 115522 Moscow, Russia
a
e-mail: bureira@mail.ru
Received October 25, 2024
Revised March 6, 2025
Accepted March 11, 2025
Abstract— Gastric cancer (GC) is one of the most common malignant tumors worldwide and ranks fifth in
the structure of cancer mortality. MicroRNAs are involved in the pathogenesis and progression of GC as
epigenetic factors, and are considered as potential noninvasive markers. We selected microRNAs involved in
the regulation of epigenetic mechanisms in GC (miR-1301-3p, miR-106a-5p, miR-129-5p, miR-3613-3p, miR-647)
and analyzed their expression in plasma of GC patients. To assess their diagnostic and prognostic potential,
we estimated correlations of differential expression with clinical and pathological characteristics of GC tu-
mors. The study included 65 plasma samples from the GC patients and 48 plasma samples obtained from
the individuals without tumor lesions, which were used as a control group. The expression was analyzed
by using real-time polymerase chain reaction (RT-PCR) method. When comparing the expression levels of
selected microRNAs in the plasma of GC patients and the control group, significant differences were found
for miR-1301-3p (p = 0.040), miR-106a-5p (p = 0.029), miR-129-5p (p < 0.0001), miR-647 (p < 0.0001). MiR-129-5p
expression was significantly associated with the prevalence of a primary tumor (p = 0.002), with the develop-
ment of metastases to regional lymph nodes (p = 0.003), and distant metastases (p = 0.003), as well as with the
late clinical stage (p = 0.003). There was a significant correlation between the miR-3613-3p expression and the
clinical stage of GC (p = 0.049). ROC analysis revealed that combining miR-106a-5p, miR-129-5p, miR-1301-3p,
and miR-647 improves diagnostic and prognostic properties of the potential panel of markers.
DOI: 10.1134/S000629792460385X
Keywords: miR-1301-3p, miR-106a-5p, miR-129-5p, miR-647, miR-3613-3p, microRNAs, gastric cancer, epigenetics,
biomarker
* To whom correspondence should be addressed.
INTRODUCTION
Gastric cancer (GC) is one of the most common
types of malignant tumors and is characterized by
high aggressiveness and mortality. In most patients,
GC is diagnosed at the late stages, when size of the
primary tumor is increased and development of the
distant metastases occurs. Therefore, search for nov-
el diagnostic and prognostic markers remains import-
ant for early diagnostics and effective treatment of
GC. Markers that can be detected in noninvasively
obtained biological material are of particular inter-
est. Differential expression of circulating microRNAs
(miRNAs) in the plasma of patients is considered as a
potential marker for various diseases, including can-
cer [1-6].
MiRNAs are short (approximately 22 nucleotides)
single-stranded non-coding sequences that control
BURE et al.672
BIOCHEMISTRY (Moscow) Vol. 90 No. 6 2025
various physiological processes and play an import-
ant role in epigenetic regulation by suppressing
translation of messenger RNA (mRNA). Differential
expression of some miRNAs is associated with clin-
ical characteristics of various types of tumors and
their treatment, which makes them interesting for
further study as prognostic biomarkers [7]. However,
miRNAs have some limitations as markers, since their
expression may vary depending on the tumor, type of
biomaterial, as well as its storage conditions, which
complicates the analysis.
Mutations in the known driver genes that are
typical for many tumors are underrepresented in GC.
Investigation of somatic mutations in the genes of
epigenetic regulation in GC confirms their important
role in the development and pathogenesis of GC [8].
Using the computer algorithm mirDIP [9] and analyz-
ing previously published data, we selected miRNAs
that target genes involved in epigenetic processes and
demonstrate differential expression in various types
of tumors. These include miR-1301-3p, miR-106a-5p,
miR-129-5p, miR-647, miR-3613-3p.
Some of the selected miRNAs were described as
participating in the development and progression of
many types of tumors. In particular, miR-1301 sup-
presses migration and invasion of tumor cells in he-
patocellular carcinoma [10], colorectal cancer [11],
and GC [12, 13]. MiR-106a demonstrates an oncogenic
effect and promotes proliferation and metastasis in
GC [14, 15], prostate cancer [16], cervical cancer [17],
and osteosarcoma [18]. MiR-129-5p, conversely, was
described as a tumor suppressor in breast cancer
[19], colon cancer [20], and GC [21]. Differential ex-
pression of miR-647 has been found in hepatocellular
carcinoma [22], colorectal cancer [23], and GC [24].
Differential expression of miR-3613-3p was observed
in the plasma of patients with retinoblastoma [25],
in the plasma and tissues of patients with colorectal
cancer [26] and GC [27].
The aim of this work was to study expression
of the selected miRNAs in the plasma of GC patients
with various clinical and pathological characteristics
of tumor growth to evaluate their potential as bio-
markers for GC.
MATERIALS AND METHODS
Patients and biomaterial. The study involved 65
GC patients, including 36 men and 29 women, with
average age of 64 years (range of years 40-83). All
patients were diagnosed and undergone surgical treat-
ment at the N. N. Burdenko Elective Surgery Clinic of
the I. M. Sechenov First Moscow State Medical Univer-
sity. The material was annotated with indication of
its localization, clinical stage, Loren classification and
TNM classification, presence or absence of signet ring
cells, as well as age, gender, and overall survival. Plas-
ma samples from 48 healthy donors with no history
of cancer were included in the investigation as a con-
trol group. All subjects gave their voluntary informed
consent for inclusion before they participated in the
study. The study was conducted in accordance with
the Declaration of Helsinki and the protocol No.04-19
approved by the Ethics Committee of Sechenov First
Moscow State Medical University (Sechenov Universi-
ty) on March 6, 2019. Clinical and pathological char-
acteristics of the patients and healthy donors are pre-
sented in Table 1.
RNA extraction and real-time polymerase chain
reaction (RT-PCR). Total RNA was extracted from the
samples by using Trizol (Life Technologies, USA) and
a miRNeasy Mini Kit (Qiagen, Germany) according to
the protocol suggested by manufacturers with small
modifications. A NanoDrop 2000 micro-volume spec-
trophotometer (Thermo Fisher Scientific, USA) was
used to estimate concentration and purity of the ob-
tained RNA.
For each sample, cDNA was synthesized from
300ng of total RNA using a MiScriptII RT Kit (Qiagen)
according to the recommended protocol. Real-time PCR
was performed with a CFX96 Real-Time PCR Detection
System (Bio-Rad, USA). Estimation of expression level
was performed in three repetitions for each transcript
and exogenous control cel-miR-39-3p, using a MiScript
SYBR Green PCR Kit (Qiagen) according to the man-
ufacturer’s protocol. Primer sequences are listed in
Table 2. Presynthesized miScript Primer Assay (Qiagen)
primer was used for cel-miR-39-3p. The obtained Ct
values were normalized and analyzed using the 2
−ΔCt
method and were presented as relative expression
units (REU) [28].
Statistical analysis. Statistical analysis of the re-
sults was performed by using Statistica13.1 program
Table 1. Clinical and pathological characteristics of
the participants
Variables
Patients
(n = 65)
Healthy
controls
(n = 48)
Gender
Female 29 (45%) 28 (58%)
Male 36 (55%) 20 (42%)
Age (years)
<49 9 (14%) 16 (33%)
>=50 56 (86%) 32 (67%)
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Table 1 (cont.)
Variables
Patients
(n = 65)
Healthy
controls
(n = 48)
T
T1 3 (5%)
T2 24 (37%)
T3 29 (44%)
T4 9 (14%)
N
N0 32 (49%)
N1 27 (42%)
N2 4 (6%)
N3 2 (3%)
M
M0 52 (80%)
M1 13 (20%)
Stage
I 3 (5%)
II 28 (43%)
III 21 (32%)
IV 13 (20%)
Survival status (n = 63)
Alive 61 (97%)
Dead 2 (3%)
Lauren classification (n = 58)
Diffuse 51 (88%)
Intestinal 7 (12%)
Signet ring cells
No 43 (66%)
Yes 22 (34%)
Tumor localization
Antral region 6 (10%)
Cardia 19 (29%)
Body 40 (61%)
Table 2. Primer sequences used to estimate microRNA
expression
Primer Sequence
miR-1301-3p 5′-AGCTGCCTGGGAGTGACTTC-3′
miR-106a-5p 5′-AAAAGTGCTTACAGTGCAGGTAGA-3′
miR-129-5p 5′-TTTTGCGGTCTGGGCTTGC-3′
miR-647 5′-TGGCTGCACTCACTTCCTTC-3′
miR-3613-3p 5′-ACAAAAAAAAAAGCCCAACCCTTC-3′
(StatSoft, USA). Normality of sample distribution was
evaluated using the Shapiro–Wilk test (for sample
sizes < 50 samples) or the Kolmogorov–Smirnov test
(for sample sizes > 50 samples). In the case of nor-
mal distribution, the results are presented as a mean
and standard deviation. When distribution was not
normal, quantitative characteristics were described
by using median (Me) and lower and upper quar-
tiles (Q1-Q3). Comparison of the two groups by a
quantitative indicator with normal distribution was
performed using the Student’s t-test; comparison of
the two groups’ variables with distribution differed
from normal was performed by the Mann–Whitney
test. The Kruskal–Wallis test was used when compar-
ing three or more groups of variables, distribution of
which differed from the normal.
A predictive model characterizing dependence
of a variable on factors was developed using linear
regression. The Kaplan–Meier method was used to
analyze overall survival. To explore potential of mi-
croRNAs as a predictive biomarker, receiver operating
characteristic curves (ROC-curves) were constructed,
and area under the curve (AUC) was examined by cal-
culating sensitivity and specificity at various threshold
levels. Potentially useful predictors have been includ-
ed in one-dimensional and multidimensional logistic
regression analysis. p < 0.05 values were considered
statistically significant.
RESULTS
Abundance of miR-1301-3p, miR-106a-5p, miR-
129-5p, and miR-647 is significantly different in
the plasma of GC patients and healthy donors.
To estimate diagnostic potential of the investigated
miRNAs, the levels of expression were quantified in
the plasma samples of GC patients and plasma sam-
ples of the individuals without tumor lesions at the
time of the study. It was shown that abundance of
miR-1301-3p in the plasma samples of GC patients was
significantly reduced compared to the control group
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BIOCHEMISTRY (Moscow) Vol. 90 No. 6 2025
Fig. 1. Expression level of miR-1301-3p(a), miR-106a-5p(b), miR-129-5p(c), miR-647(d), and miR-3613-3p(e) in the plasma
of GC patients and healthy donors. *Statistically significant p-values.
(p=0.040) (Fig.1a). A statistically significant increase
in the miR-106a-5p expression was found in the plas-
ma samples of GC patients compared to the control
(p=0.029) (Fig.1b). Abundance of the miR-129-5p was
significantly higher in the plasma of GC patients com-
pared to the control (p < 0.0001) (Fig. 1c), as well as
abundance of the miR-647 (p < 0.0001) (Fig. 1d). No
significant difference was found for the miR-3613-3p
(p = 0.056) (Fig. 1e).
Expression levels of miR-129-5p and miR-3613-3p
in the GC plasma samples are associated with clin-
ical and pathological characteristics of GC patients.
To determine significant factors related to the clinical
course of GC, we analyzed potential associations be-
tween the expression of circulating miRNAs and clini-
cal and pathological characteristics of the GC patients.
It was found that the increased expression of
miR-129-5p was associated with the larger tumor size
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Fig. 2. Associations of abundance of miR-106a-5p, miR-129-5p,
miR-3613-3p, miR-1301-3p, miR-647 in the plasma of GC pa-
tients and healthy donors, as well as combinations of miRNAs
that showed the best results (miR-129-5p, miR-1301-3p,
miR-647).
(T3-T4 group) according to the TNM classification
(p = 0.002), metastasis to regional lymph nodes (N1-3)
(p = 0.003), distant M1 metastases (p = 0.003), as well
as later GC stages (stageIII-IV) (p = 0.003). MiR-3613-3p
was also associated with the advanced stages of GC
(stage III-IV) (p = 0.049). When comparing with oth-
er characteristics (gender, age, overall survival, Loren
classification, the presence of the signet ring cells),
no significant correlations were found. Presence of
the signet ring cells is a characteristic of the gastric
signet ring cell carcinoma with low differentiation
of tumor cells. It is an unfavorable histological sub-
type of GC that progresses rapidly, metastasizes ear-
ly, and has worse prognosis compared to the other
subtypes.
There were also no significant associations when
comparing expression of the miR-106a-5p, miR-647,
and miR-1301-3p in the plasma of GC patients with
different clinical and pathological characteristics. The
results of all estimated correlations are presented
in Table S1 in the Online Resource 1.
Diagnostic value of miRNAs was confirmed by
ROC-curves and analysis of the AUC. To estimate po-
tential diagnostic and prognostic value of the miRNAs
in GC, ROC-curves were used. When analyzing differ-
entiation between the groups of GC patients and the
healthy donors, the best result was shown for combi-
nation of miR-129-5p, miR-1301-3p, and miR-647, for
which AUC was 0.90 (confidence interval [95% CI]:
0.90-0.91), sensitivity 83%, and specificity 83%, accu-
racy 83% (Fig.2).
Expression of miR-1301-3p, miR-106a-5p, miR-
129-5p, miR-647, and miR-3613-3p in the plasma of GC
patients was compared with their clinical and patho-
logical characteristics. MiRNAs that showed significant
differences were further analyzed by one-dimensional
logistic regression analysis to calculate AUC with sta-
tistical significance level of more than 0.5.
The ROC-curves and AUC values obtained for all
investigated miRNAs and clinical and pathological
characteristics of GC patients are presented in Fig. 3.
For each of the characteristics, combination of only
those miRNAs that showed the best combined result
is shown. In particular, the AUC for miR-106a-5p, miR-
129-5p, miR-647 and the primary tumor size T was
0.72 (confidence interval [95% CI]: 0.71-0.74), sensitiv-
ity 70%, specificity 62% and accuracy 65% (Fig.3a).
Analysis of the ROC-curve of miR-106a-5p, miR-
129-5p, miR-647 and the development of metasta-
ses to regional lymph nodes showed an AUC of 0.76
([95%CI]: 0.75-0.77), sensitivity of 88% and specificity
of 56%, accuracy of 71% (Fig. 3b). The AUC for miR-
106a-5p, miR-129-5p and the development of distant
metastases was 0.76 ([95% CI]: 0.75-0.8), sensitivity
89% and specificity 60%, accuracy 84% (Fig. 3c). The
AUC for miR-106a-5p, miR-647 and signet ring cells
was 0.64 ([95% CI]: 0.63-0.66), sensitivity 96% and
specificity 30%, accuracy 74% (Fig.3d).
Combination of miR-106a-5p, miR-129-5p, and
miR-647 and clinical stage of the GC patients gave
the AUC of 0.72 ([95% CI] 0.71-0.73), sensitivity 76%,
specificity 53%, accuracy 64% (Fig.3e).
DISCUSSION
In recent years, more and more studies confirm
important role of ncRNAs in the GC pathogenesis.
Aberrant expression of some of them could be con-
sidered as one of the key events in carcinogenesis,
which makes them promising biomarkers.
To analyze the miRNA-target gene pairs, we
used the computer algorithm mirDIP (http://ophid.
utoronto.ca/mirDIP/), which is able to integrate data
on almost 152 million target pairs collected from 30
different resources, therefore providing high degree
of reliability [9]. As a result, 407 miRNAs were pre-
dicted, and each of them can regulate several genes
of epigenetic regulation simultaneously. Based on the
obtained data, miR-106a-5p, miR-129-5p, miR-3613-3p,
miR-647, and miR-1301-3p were selected for further
investigation as potential regulators of some genes of
epigenetic regulation. Among them are genes involved
in DNA methylation/demethylation, histone modifica-
tions, and chromatin remodeling (Fig. 4). In the pre-
vious work, we have demonstrated importance of
somatic mutations in these genes for the GC devel-
opment and progression [8], whereas this study was
devoted to the role of epigenetic factors as biomarkers
for GC.
A significant advantage of miRNAs is their ability
to circulate in body fluids. Serum or plasma samples
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BIOCHEMISTRY (Moscow) Vol. 90 No. 6 2025
Fig. 3. Associations of miR-106a-5p, miR-129-5p, miR-3613-3p, miR-1301-3p, miR-647 with clinical and pathological character-
istics of the GC patients, as well as combinations of miRNAs that showed the best results: miR-106a-5p, miR-129-5p, miR-647
with the primary tumor size (a), miR-106a-5p, miR-129-5p, miR-647 with the development of metastases to regional lymph
nodes (b), miR-106a-5p, miR-129-5p with the development of distant metastases (c), miR-106a-5p, miR-647 with signet ring
cells (d); miR-106a-5p, miR-129-5p, miR-647 with the clinical stage (e). The receiver operating characteristic (ROC-curves).
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Fig. 4. MiRNAs and their target genes involved in epigenetic regulation (genes associated with DNA methylation are high-
lighted in red, genes regulating histone modifications are highlighted in blue, genes regulating chromatin remodeling are
highlighted in green).
are relatively easily available, and miRNAs are able
to withstand adverse physiological conditions, includ-
ing pH changes, high temperature, and freeze/thaw
cycles. Therefore, circulating miRNAs in plasma are
considered as promising biomarkers for non-inva-
sive diagnosis and prognosis. Expression patterns of
miRNA in plasma allow identification of various types
of tumors, including GC. To assess diagnostic and prog-
nostic potential of the selected miRNAs (miR-1301-3p,
miR-106a-5p, miR-129-5p, miR-647, and miR-3613-3p),
we investigated their expression in the plasma of GC
patients compared to the healthy donors, as well as
their potential associations with clinical and patholog-
ical characteristics.
In our study, the expression level of miR-1301-3p
in the plasma samples of GC patients was significant-
ly lower compared to the control group (p = 0.040).
It has been shown previously that overexpression of
miR-1301-3p suppresses migration, invasion, and pro-
liferation of GC cells [12, 13]. In addition, miR-1301
expression was associated with survival of the pa-
tients with hepatocellular carcinoma [29], however,
in our study, no significant associations with the clin-
ical and pathological characteristics of the GC patients
were found.
We found a significant increase of the miR-106a-
5p expression level in the plasma of GC patients com-
pared to the control (p = 0.029), which is in concor-
dance with the previous studies. Wang et al. showed
that overexpressed miR-106a could play an oncogen-
ic role in the GC carcinogenesis [14, 30]. In another
study, the miR-106a expression level was significantly
higher in the plasma samples of GC patients compared
with the plasma from healthy donors [31], which is
in concordance with our results. Some authors con-
firmed that the increased miR-106a expression is as-
sociated with metastasis and epithelial-mesenchymal
transition [32], as well as with tumor differentiation,
lymph node metastasis, and tumor size [31]. In our
study, no correlations of the miR-106a-5p expression
with clinical and pathological characteristics of the GC
patients were found.
The miR-129-5p expression was significantly dif-
ferent in the plasma samples of GC patients compared
with the control group (p < 0.0001). Both increased
and decreased expression was observed in different
samples, but the average value was higher in the
GC patients than in the control group. This result
differs from the values obtained by other research-
ers, as miR-129-5p expression has been reported to
be decreased in the tumor tissues and blood of the
GC patients compared with the corresponding non-
tumor adjacent tissues and healthy donors [33]. The
miR-129-5p expression level was significantly lower
in the GC tissues than in the adjacent non-tumor tis-
sues, and also lower in the GC cell lines compared
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BIOCHEMISTRY (Moscow) Vol. 90 No. 6 2025
with the normal epithelial cells of gastric mucosa [34].
MiR-129-5p suppresses invasion and proliferation of
the GC cells [35]. Yu et al. found that the increased
level of miR-129-5p in the GC cells delays the cell cy-
cle at the G0/G1 phase, showing suppressive activity
against the tumor [36]. Some studies also mentioned
both increase and decrease of the miR-129-5p expres-
sion [37], as it was in our investigation, but it was
mainly related to the tumor tissues of hepatocellular
carcinoma.
As a result of our statistical analysis, it was shown
that the miR-129-5p expression was significantly as-
sociated with the primary tumor size, development
of metastases to regional lymph nodes and distant
metastases, as well as with the clinical stage of GC.
ThemiR-129-5p expression has previously been associ-
ated with the tumor size and invasion of lymph nodes,
and poor prognosis in the GC patients [38].
The level of miR-647 expression was significantly
different in the plasma samples of GC patients com-
pared with the control group (p < 0.0001). MiR-647 is
known to act as a tumor suppressor in GC, suppressing
invasion and metastasis [39]. We did not find a signif-
icant statistical association of the miR-647 expression
level in plasma of the GC patients with clinical and
pathological characteristics, although in some stud-
ies the miR-647 expression was significantly changed
in the patients with GC metastases in the lymph
nodes [40]. Previously, we reported association of the
miR-647 expression with the primary tumor size of GC
patients, but we did not find significant differences
between the expression levels in the tumor and adja-
cent non-tumor tissues of GC patients and the section-
al samples of gastric tissue (control) [41].
In our study, no significant difference in the miR-
3613-3p expression was found between the plasma sam-
ples of GC patients and the control group (p = 0.056),
although it was previously demonstrated that the
miR-3613-3p level was significantly lower in the tumor
tissues and serum of the patients with breast cancer.
Functional studies have shown that miR-3613-3p could
act as a tumor suppressor and restrain its progres-
sion by regulating the cell cycle [42]. In addition, it
was found that miR-3613-3p overexpression causes
significant suppression of several genes with tumor
suppression potential (encoding apoptotic protease
activating factor 1 (APAF1), Dicer, DNA fragmentation
factor β subunit, von Hippel–Lindau protein, and neu-
rofibromin 1) in the human neuroblastoma cells [43].
Analysis of correlations of the miR-3613-3p levels in
plasma with the clinical and pathological characteris-
tics of the GC patients demonstrated a tendency to be
increased at the late stages of GC (stage III+IV) with
low statistical significance (p = 0.049). Small amount
of the available data and their ambiguity suggests an
unclear role of miR-3613-3p in GC [27].
At present, profiles of miRNA expression are
being actively studied in different types of tumor to
form a system that will allow determining presence
of a tumor, its stage and presence of metastases, as
well as assessing sensitivity to the chosen therapy.
There are numerous papers presenting miRNAs as po-
tential markers that could be used for diagnosis and
prognosis of tumors progression with high sensitivity
and specificity [44-46]. Many studies have shown that
using combination of miRNAs as a marker generally
increases its sensitivity and specificity, and also allows
combining diagnostic and prognostic properties of the
individual miRNAs providing a more accurate assess-
ment of the disease in each specific case.
Construction of ROC-curves is widely used to
assess diagnostic potential of biomarkers both indi-
vidually and in panels. We performed a one-dimen-
sional logistic regression analysis for miR-1301-3p, miR-
106a-5p, miR-129-5p, miR-647, and miR-3613-3p in the
plasma of GC patients and healthy donors, as well as
in association with the clinical and pathological charac-
teristics of the GC patients. As a result, the assumption
that combination of miRNAs in panels increases their
specificity and sensitivity was confirmed. In particular,
the use of miR-129-5p, miR-1301-3p, and miR-647 com-
bination in analysis of differentiation between the GC
patients and healthy donors showed the AUC values
of 0.9 and sensitivity and efficacy values above 0.8,
which significantly exceeded the AUC values for each
individual miRNA (0.78, 0.54, and 0.73, respectively).
The combination of miR-106a-5p, miR-129-5p, and
miR-647 increases sensitivity and specificity when es-
timating the primary tumor size, clinical stage of the
disease, development of metastases to regional lymph
nodes, and distant metastases, although the results of
ROC analysis show average efficacy. In particular, we
have revealed potential of the panel of miR-129-5p,
miR-1301-3p, miR-647 as a diagnostic system, and the
miR-106a-5p, miR-129-5p, miR-647 panel as a predic-
tive model for several clinical characteristics of the
patients with GC.
It is known that analysis of the ROC-curve for
miR-106a has previously demonstrated high sensi-
tivity and specificity in the diagnosis of GC [31, 47].
Inthe study of gastric juice samples from GC patients,
the AUC for miR-129-1-3p and miR-129-2-3p was 0.639
and 0.651, respectively, while for their combination
the AUC reached 0.656 [48]. High efficiency and sensi-
tivity of the miR-647 level in the serum of GC patients
as a diagnostic biomarker [49] and of the miR-1301-3p
level in the papillary thyroid cancer [50] has been also
demonstrated previously.
MiRNAs play a complex role in oncogenesis, there-
fore their mechanisms of action and functions still re-
main not fully understood. Besides, there are some
limitations in using circulating miRNAs as diagnostic
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BIOCHEMISTRY (Moscow) Vol. 90 No. 6 2025
and prognostic biomarkers. Among them are low con-
centrations of miRNAs in plasma and serum, insuf-
ficiently accurate methods for quantifying miRNAs,
and lack of the standard methods for normalization.
Overcoming of these limitations is associated with cer-
tain challenges. Our data suggest potential diagnostic
and prognostic significance of miR-106a-5p, miR-129-
5p, miR-1301-3p, and miR-647 in gastric carcinogene-
sis, however, this requires further investigation.
CONCLUSIONS
Like the other types of tumors, patients with GC
have better prognosis when it is diagnosed at an ear-
ly stage and a patient obtains an optimal treatment.
Thus, application of effective diagnostic and prog-
nostic biomarkers for early diagnosis could increase
long-term survival of GC patients. A profile of dif-
ferentially expressed miRNAs associated with clini-
cal and pathological characteristics of GC patients in
plasma or serum samples could be used for noninva-
sive diagnosis and postoperative monitoring. In our
work, we revealed statistically significant differences
between the expression levels of miR-1301-3p, miR-
106a-5p, miR-129-5p, and miR-647 in the plasma of GC
patients and in the control group. Moreover, associa-
tions with clinical and pathological characteristics of
the GC patients were found for miR-129-5p and miR-
3613-3p. Combining of miR-129-5p, miR-1301-3p, and
miR-647 into a panel improved their diagnostic prop-
erties, and combination of miR-106a-5p, miR-129-5p,
and miR-647 increased their sensitivity and specificity
in predicting several clinical and pathological charac-
teristics. Thus, our data suggest potential diagnostic
and prognostic value of the miR-106a-5p, miR-129-5p,
miR-1301-3p, and miR-647 panel in GC, which requires
additional investigation.
Abbreviations. AUC, area under the curve; GC,
gastric cancer; ROC-curves, receiver operating charac-
teristic curves.
Supplementary information. The online version
contains supplementary material available at https://
doi.org/10.1134/S000629792460385X.
Contributions. M. V. Nemtsova and I. V. Bure –
concept and curation of the work; E. A. Vetchinkina,
E. B. Kuznetsova, E. A. Alekseeva, and N. S. Esetov – ex-
periments; A. E. Kiseleva – obtaining plasma samples
and processing tables with clinical and pathological
characteristics of patients; A. I. Kalinkin – computa-
tional analysis of the results; E. A. Vetchinkina, M. V.
Nemtsova, and I. V. Bure – writing text of the paper.
Funding. This work was financially supported
by the Russian Science Foundation (project no. 20-75-
10117-П).
Ethics approval and consent to participate. The
study was conducted in accordance with the Declara-
tion of Helsinki and the protocol No.04-19 approved
by the Ethics Committee of Sechenov First Moscow
State Medical University (Sechenov University) on
March 6, 2019. All subjects gave their voluntary in-
formed consent for inclusion before they participated
in the study.
Conflict of interest. The authors of this work de-
clare that they have no conflicts of interest.
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