ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ
Background. Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clin...
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Experimental Oncology| _version_ | 1868113233280237568 |
|---|---|
| author | Martyniuk, О. Mushii, O. Pavlova, A. |
| author_facet | Martyniuk, О. Mushii, O. Pavlova, A. |
| author_institution_txt_mv | [
{
"author": "О. Martyniuk",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, the National Academy of Sciences of Ukraine, Kyiv, Ukraine"
},
{
"author": "O. Mushii",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, the National Academy of Sciences of Ukraine, Kyiv, Ukraine"
},
{
"author": "A. Pavlova",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, the National Academy of Sciences of Ukraine, Kyiv, Ukraine"
}
] |
| author_sort | Martyniuk, О. |
| baseUrl_str | https://exp-oncology.com.ua/index.php/Exp/oai |
| collection | OJS |
| datestamp_date | 2026-06-15T10:40:17Z |
| description | Background. Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clinical signifi ance of circulating and tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insuffi    tly elucidated. Materi- als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis- sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic signifi ance was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re- sults. young BC patients (≤45 years) demonstrated signifi antly lower circulating levels of both miRNAs. Serum hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa- miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres- sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub- type and lymph node involvement, with the highest expression observed in hER2-positive tumors and in patients with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confi med its predictive value (AUC =  0.750 for serum and 0.818 for tumor tissue). No signifi ant association between hsa-miR-26b-5p and chemothe- rapy response was observed. Conclusions. hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients. |
| doi_str_mv | 10.15407/exp-oncology.2026.01.031 |
| first_indexed | 2026-06-15T01:00:20Z |
| format | Article |
| fulltext |
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 31
Original Contribution
C i t a t i o n: Martyniuk O, Mushii O, Pavlova A. Integrated analysis of hsa-miR-26b-5p and hsa-miR-186-5p in blood
serum and tumor tissue reveals their prognostic and predictive significance in breast cancer. Exp Oncol. 2026; 48(1): 31-
39. https://doi.org/10.15407/exp-oncology.2026.01.031
© PH “Akademperiodyka” of the NAS of Ukraine, 2026. This is an open access article under the CC BY-NC-ND license
(https://creativecommons.org/licenses/by-nc-nd/4.0/)
https://doi.org/10.15407/exp-oncology.2026.01.031
О. Martyniuk, O. Mushii *, A. Pavlova
R.E. Kavetsky Institute of Experimental Pathology,
Oncology and Radiobiology, the National Academy
of Sciences of Ukraine, Kyiv, Ukraine
* Correspondence: E-mail: sashamushy1@gmail.com
Integrated Analysis of hsa-miR-26b-5p
and hsa-miR-186-5p in Blood Serum and
Tumor Tissue Reveals their Prognostic and
Predictive Significance in Breast Cancer
Background. Breast cancer (BC) heterogeneity significantly complicates diagnosis, prognosis, and prediction of
treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu-
mor progression and in regulating therapy sensitivity. However, the combined clinical significance of circulating and
tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insufficiently elucidated. Materi-
als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis-
sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic significance
was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in
patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re-
sults. Young BC patients (≤45 years) demonstrated significantly lower circulating levels of both miRNAs. Serum
hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular
subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa-
miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres-
sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors
and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub-
type and lymph node involvement, with the highest expression observed in HER2-positive tumors and in patients
with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced
sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confirmed its predictive value (AUC =
= 0.750 for serum and 0.818 for tumor tissue). No significant association between hsa-miR-26b-5p and chemothe
rapy response was observed. Conclusions. hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles
in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas
hsa-miR-186-5p reflects its molecular characteristics and response to chemotherapy. Their combined assessment
in serum and tumor tissue represents a promising approach for improving prognostic stratification and predicting
treatment efficacy in BC patients.
Keywords: breast cancer, hsa-miR-26b-5p, hsa-miR-186-5p, doxorubicin.
32 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
О. Martyniuk, O. Mushii, A. Pavlova
Breast cancer (ВС) is a clinically heterogeneous di
sease characterized by substantial variability in ther-
apeutic response, even within the same molecular
subtype [1]. Despite the widespread use of anthracy-
cline-based regimens, including doxorubicin, intrin-
sic and acquired resistance remain major limitations
affecting treatment efficacy and patient outcomes [2].
This highlights the need for robust molecular mark-
ers that not only reflect tumor biology but also pre-
dict individual response to systemic therapy.
Recent advances in molecular oncology have
emphasized the importance of the regulatory RNA
networks in shaping tumor behavior and drug sen-
sitivity. Among these, microRNAs (miRNAs) act as
fine-tuners of gene expression and are involved in
multiple oncogenic pathways, including epithelial–
mesenchymal transition, apoptosis, and modula-
tion of the tumor microenvironment [3]. Impor-
tantly, certain miRNAs have been shown to simul-
taneously influence tumor progression and
response to chemotherapy, suggesting their poten-
tial as dual-function biomarkers [4].
In this context, hsa-miR-26b-5p and hsa-miR-
186-5p are promising candidates due to their re-
ported tumor-suppressive properties and involve-
ment in key signaling pathways associated with
proliferation, invasion, and chemoresistance in ВС
[5—7]. However, their integrated clinical relevance,
particularly in relation to neoadjuvant chemother-
apy response, remains insufficiently explored.
Our previous studies indicate that using miRNAs
as diagnostic and prognostic cancer markers is a
promising approach, particularly as medical oncol-
ogy actively moves toward a personalized model
[8—10]. Given the great potential of miRNAs as
marker molecules, the aim of our study was to vali-
date the use of hsa-miR-26b-5p and hsa‑miR‑186‑5p
for diagnosis, prognosis of disease course, and pre-
diction of the effectiveness of neoadjuvant chemo-
therapy of BC patients.
Materials and Methods
Malignant tissue samples were obtained from BC pa-
tients (n = 124) who were treated at the National
Cancer Institute of the Ministry of Health of Ukraine
between 2019 and 2022. The blood samples and tu-
mor biopsies were collected from all patients before
therapy initiation. A subset of patients received neo-
adjuvant therapy according to the 4AC regimen, and
in these cases, the material was used to assess the re-
lationship between miRNA expression levels and
doxorubicin sensitivity (Table). All patients subse-
quently underwent standard therapeutic interven-
tions, and disease recurrence was monitored over a
3-year follow-up period. The comparison group was
Clinicopathological characteristics of the BC patients
Characteristics n %
Number of patients 124 100
Average age 49.44 ± 12.32
Age range 20—77
Reproductive status
Perimenopause 33 73.4
Menopause 91 26.6
BC stage
І 25 20.2
ІІ 66 53.2
ІІІ 19 15.3
ІV 14 11.3
Category N according to ТNM
N0 83 66.9
N1-3 41 33.1
Category M according to ТNM
M0 111 89.5
M1 13 10.5
Tumor grade
G1 11 8.9
G2 94 75.8
G3 19 15.3
3-year progression
No progression 113 91.1
Progression 11 8.9
Molecular subtype
Luminal A 20 16.1
Luminal B 73 58.9
Her2/neu-positive 17 13.7
Basal 14 11.3
Miller—Payne pathological
complete response grade
V 14 18.4
IV 17 22.3
III 19 25.0
II 22 28.9
I 4 5.4
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 33
Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue
composed of 10 fibroadenoma samples and 5 condi-
tionally normal breast tissue samples. The study was
approved by the Institutional Review Board and Re-
search Ethics Committee of R.E. Kavetsky Institute
of Experimental Pathology, Oncology and Radiobio
logy of the National Academy of Sciences of Ukraine
and conducted in accordance with the Declaration of
Helsinki and Good Clinical Practice guidelines. All
patients provided written informed consent for the
use of clinical data for research purposes. Clinical
and pathological characteristics of the studied BC
cases are detailed in the Table. The therapeutic re-
sponse in BC cases was evaluated using the Miller—
Payne grading system, which provides a standardized
morphological measure of treatment efficacy.
miRNA expression was analyzed using real-time
PCR. Formalin-fixed paraffin-embedded (FFPE)
tumor biopsy samples and blood serum samples
were used for the assessment. Total RNA was ex-
tracted from the FFPE tissue sections using an
RNeasy FFPE Kit (QIAGEN, Germany) and from
blood samples using a NucleoSpin kit (MACHE-
REY-NAGEL, Germany) according to the manu-
facturer’s instructions. RNA concentration was
measured with a NanoDrop 1000 Spectrophoto
meter (Thermo Scientific, USA), and the purity
was assessed by the 260/280 nm absorbance ratio.
Isolated RNA was dissolved in Tris-EDTA buffer
and stored at –20 °C until further use.
Complementary DNA was synthesized from
100 ng of total RNA using the LunaScript® RT Super-
Mix Kit (New England Biolabs, USA). RNU48 small
nucleolar RNA was employed as an endogenous cont
rol to normalize miRNA expression levels. Primers for
the target RNAs were synthesized by YP Biotech
(Ukraine) according to the sequences: RNU48 for-
ward 5′-AGT GAT GAT GAC CCC AGG TAA CTC-
3′ and reverse 5′-CTG CGG TGA TGG CAT CAG-3′;
hsa-miR-26b-5p forward 5′-GTT TGG GTT CAA
GTA ATT CAG G-3′ and universal reverse; hsa-miR-
286-5p forward 5′-GTT TGG GTT CAA GTA ATT
CAG G-3′ and universal reverse.
Quantitative real-time PCR was performed us-
ing a QuantStudio 5 Dx Real-Time PCR System
(Thermo Fisher Scientific, USA) and a LunaScript®
MasterMix Kit (New England Biolabs, USA). Each
sample was analyzed in triplicate, and the threshold
cycle (Ct) values were averaged. Relative miRNA
expression was calculated using the 2–ΔCt method,
as previously described [11].
Comparisons between two groups were per-
formed using the Mann—Whitney U test, while
comparisons among three or more groups were
conducted using the Kruskal—Wallis test followed
by post hoc analysis. Receiver operating characte
ristic (ROC) curve analysis was performed to eva
luate the predictive performance of selected markers
according to neoadjuvant chemotherapy (NAC) ef-
fectiveness. Statistical analyses were conducted us-
ing GraphPad Prism 10 (GraphPad Software,
USA), and p-values < 0.05 were considered statis-
tically significant.
Results
Prognostic and predictive value of circulating hsa-
miR-26b-5p and hsa-miR-186-5p expression in se-
rum of breast cancer patients. At the first stage, we
investigated the expression of circulating hsa-miR-
26b-5p and hsa-miR-186-5p in the serum of BC pa-
tients to verify their prognostic significance (Fig. 1).
We revealed that young BC patients (≤45 years)
were characterized by significantly lower levels of
hsa-miR-26b-5p and hsa-miR-186-5p by 2.15-fold
(p = 0.0274) and 37.5-fold (p = 0.0241), respectively.
At the same time, the expression of hsa-miR-186-5p
in the serum of patients with stage I BC was signifi-
cantly higher by 8.32-fold (p = 0.0456) compared to
the corresponding values in patients with stage II
BC. No association between circulating hsa-miR-
26b-5p levels and disease stage was found. We estab-
lished that the highest expression levels of hsa-miR-
186-5p in serum were characteristic of BC patients
with the T1 and T3 categories (p = 0.0475).
An association between the levels of the studied
miRNAs and the regional lymph node involvement
was demonstrated. In patients with the N0 catego-
ry, the expression levels of hsa-miR-26b-5p were
significantly decreased by 1.96-fold (p = 0.0113),
and those of hsa-miR-186-5p increased by 3.93‑fold
(p = 0.0109), compared to the cohort of patients
with the diagnosed regional lymph node involve-
ment (N1—3 category).
The relationship between circulating hsa-miR-
26b‑5p levels and the BC grade is worth noting.
We observed significantly higher levels of this
miRNA (3.53‑fold, p = 0.02) in the serum of pa-
tients with well-differentiated BC compared to the
blood samples from patients with poorly differen-
tiated breast tumors. In addition, the relationship
34 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
О. Martyniuk, O. Mushii, A. Pavlova
between hsa-miR-186-5p expression levels and mo-
lecular subtype was shown. In patients with lumi-
nal B BC, the expression of this miRNA was higher
by 22.9-fold (p = 0.0178), 5.74-fold (p = 0.0199),
and 11.84-fold (p = 0.0089) compared to patients
with the luminal A, HER2/neu-positive, and tri-
ple-negative subtypes, respectively.
The prognostic value of the studied miRNAs for
assessing the risk of disease progression was also
demonstrated. In the serum of BC patients who ex-
perienced disease progression within 3 years after
primary diagnosis, the levels of hsa-miR-26b-5p
significantly increased by 2.15-fold (p = 0.0246),
while circulating hsa-miR-186-5p levels decreased
by 5.19-fold (p = 0.0438), compared to patients
without documented progression. No associations
were found in BC patients between circulating hsa-
miR-26b-5p and hsa-miR-186-5p levels and repro-
ductive status, tumor size, or clinical stage.
We further assessed the predictive value of the
studied circulating serum miRNAs in BC patients un-
dergoing 4AC therapy. It was shown that patients with
significantly higher levels of circulating hsa-miR-186-
5p (11.29-fold, p = 0.0495) were characterized by a
significant decrease in sensitivity to doxorubicin.
Meanwhile, the area under the ROC curve (AUC) for
this miRNA was 0.750 (SE = 0.102), indicating high
discriminative ability of the biomarker. The 95% con-
fidence interval (0.5508 to 0.9492) confirmed a stable
trend toward discrimination between sensitive and
resistant tumors, and the observed differences were
significant (p = 0.0476). At the same time, no relation-
ship between serum hsa-miR-26b-5p level and sensi-
tivity to doxorubicin was revealed (Fig. 2).
Diagnostic, prognostic, and predictive value of
the expression of tumor-associated hsa-miR-26b-5p
and hsa-miR-186-5p in breast tumor tissue. At the
next stage of the study, we evaluated the expression
Fig. 1. Relationship between circulating serum levels of hsa-miR-26b-5p or hsa-miR-186-5p and clinical status of BC
patients. * p < 0.05
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 35
Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue
levels of tumor-associated miRNAs to determine
their diagnostic, prognostic, and predictive potential
in BC. A characteristic feature of fibroadenoma tissue
was significantly higher expression levels of hsa-miR-
186-5p (2.05-fold, p = 0.0223) compared to BC sam-
ples. The differences in hsa-miR-26b-5p expression
depending on the type of breast tissue were insignif-
icant (Fig. 3).
We also demonstrated that BC tissue samples from
young patients were characterized by increased ex-
Fig. 2. Serum levels of hsa-miR-26b-5p (a) and hsa-miR-186-5p (b) depending on the response to NAC with doxorubi-
cin (upper panels), and the corresponding ROC curves (lower panels) reflecting the predictive ability of these miRNAs
for BC sensitivity to treatment. * p < 0.05
Fig. 3. Expression of hsa-miR-26b-5p (a) and hsa-miR-186-5p (b) in conditionally normal breast tissue, fibroadenoma,
and BC tissue. * p < 0.05
36 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
О. Martyniuk, O. Mushii, A. Pavlova
pression levels of hsa-miR-26b-5p (1.76-fold, p =
= 0.0005) compared to those from patients older than
45 years. In addition, a tendency toward decreased
expression of tumor-associated hsa-miR-26b-5p (p =
= 0.030) with increasing tumor stage was observed.
An association between the expression of the stud-
ied miRNAs in tumor tissue and tumor size was es-
tablished (Fig. 4). In particular, BC tissue of the T2
category was characterized by significantly higher lev-
els of hsa-miR-26b-5p (9.06-fold, p = 0.0036), accom-
panied by a decrease in hsa-miR-186-5p levels
(2.4‑fold, p = 0.0216) compared to those of tumors of
the T4 and T3 categories, respectively. It is worth not-
ing a general trend toward an increased hsa-miR-186-
5p expression along with decreased hsa-miR-26b-5p
levels with increasing tumor size.
We found that BC with diagnosed regional lymph
node involvement is characterized by significantly
higher hsa-miR-186-5p expression levels in tumor
tissue (1.92-fold, p = 0.0262) compared to BC of the
N0 category. At the same time, the decreased expres-
sion of hsa-miR-26b-5p was associated with the
presence of distant metastases. In the M1 category
cases, the expression of this miRNA was 3.79-fold
lower (p = 0.0216) compared to the M0 category.
A significant increase in hsa-miR-26b-5p levels
(4.25-fold, p = 0.0202 and 2.14-fold, p = 0.0471)
was observed in poorly differentiated BC tissue
compared to tumor samples of highly and moder-
ately differentiated tumors, respectively. The high-
est levels of this miRNA (4.01-fold, p = 0.0069 and
7.18-fold, p = 0.0118) were detected in luminal B
BC tissue compared to HER2/neu-positive and tri-
ple-negative molecular subtypes, respectively.
An increase in tumor-associated hsa-miR-186-
5p expression was shown in HER2/neu-positive BC
(2.23-fold, p = 0.0450) compared to the luminal B
subtype. No significant association between the ex-
Fig. 4. Relationship between expression levels of tumor-associated hsa-miR-26b-5p or hsa-miR-186-5p and clinical
status of BC patients. * p < 0.05
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 37
Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue
pression levels of the studied miRNAs and the his-
tological type of BC was found.
In addition, the prognostic role of hsa-miR-186-
5p expression levels in BC tissues was demonstrat-
ed. The patients with recurrence within 3 years af-
ter primary diagnosis were characterized by signifi-
cantly higher expression levels of this miRNA in
tumor tissue (3.29-fold, p = 0.0262).
No association was found between the expres-
sion levels of the studied miRNAs in tumor tissue
and menopausal status or tumor stage.
At the final stage, we evaluated the relationship
between the levels of the studied miRNAs in tumor
tissues and the effectiveness of NAC in BC patients
treated with doxorubicin (Fig. 5). The patients who
exhibited nonresponse or partial response to 4AC
therapy (Miller—Payne grade I—III) were charac-
terized by significantly higher expression levels of
hsa-miR-186-5p in BC tissues (2.09-fold, p = 0.0203)
compared to the patients who responded to chemo-
therapy (Miller—Payne grade IV—V). No associa-
tion between NAC effectiveness and hsa-miR-
26b‑5p expression levels was observed.
Finally, ROC analysis was performed to evaluate
the predictive value of the studied miRNAs for sen-
sitivity to 4AC therapy. AUC was 0.818 (SE = 0.103),
indicating high discriminative ability of the biomark-
er. The 95% CI (0.616—1.000) confirmed a stable
trend toward discrimination between sensitive and
resistant tumors. The observed differences were sig-
nificant (p = 0.0208), indicating the potential of hsa-
miR-186-5p as a predictive marker of NAC response.
The results of the study demonstrated the coordi-
nated changes in the levels of hsa-miR-26b-5p and
hsa-miR-186-5p in both serum and tumor tissues of
BC patients, reflecting clinicopathological characte
ristics and tumor behavior. The young patients and
those with poorly differentiated tumors exhibited in-
Fig. 5. Levels of hsa-miR-26b-5p (a) and hsa-miR-186-5p (b) in BC tissues depending on the response to NAC with
doxorubicin (upper panels), and the corresponding ROC curves (lower panels) reflecting the predictive ability of these
miRNAs for the BC sensitivity to the treatment. * p < 0.05
38 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
О. Martyniuk, O. Mushii, A. Pavlova
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creased levels of hsa-miR-26b-5p in both serum and
tumor tissue, whereas hsa-miR-186-5p showed the
highest expression in HER2/neu-positive tumor tis-
sue and in the serum of patients with early-stage BC,
indicating its specific association with the tumor
molecular profile and local activity.
The elevated serum levels of hsa-miR-26b-5p
were associated with BC progression, while the
high levels of hsa-miR-186-5p in peripheral blood
and tumor tissue correlated with recurrence and
resistance to NAC.
The results obtained are consistent with current
evidence of the involvement of the studied miRNAs
in the regulation of the tumor microenvironment
and carcinogenesis. In particular, hsa-miR-26b-5p is
considered an important regulator of extracellular
matrix genes and metabolic cascades, as demonstrat-
ed in pancreatic cancer [12], hepatocellular carcino-
ma [13], and non-small cell lung cancer [14], as well
as in malignant tumors of the uterus [15]. Moreover,
its increased expression after prolonged radiation
exposure is associated with enhanced DNA repair
and increased migratory and invasive potential of
tumor cells, highlighting its link with adaptive tumor
stress responses [7]. Meanwhile, hsa-miR-186-5p
has been described as a key regulator of the TGFβ
signaling pathway through suppression of SMAD6/
SMAD7 and is involved in the pathogenesis of co
lorectal [16], hepatocellular [17], endometrial and
ovarian [18], lung [19], and esophageal [20] cancers,
indicating its broad involvement in tumor progres-
sion signaling networks. Despite accumulating evi-
dence regarding the functional roles of both miRNAs
in multiple tumor types, their prognostic and diag-
nostic value remains insufficiently characterized,
underscoring the need for further research into their
potential as biomarkers.
The combined analysis of these miRNAs sug-
gested that hsa-miR-2a6b-5p could be involved in
tumor aggressiveness and systemic response,
whereas hsa-miR-186-5p expression is related to
the molecular characteristics and NAC sensitivity.
This integrated pattern highlights the potential of
both miRNAs as biomarkers for the simultaneous
assessment of progression risk, molecular subtype,
and the prediction of treatment response, making
them promising candidates for comprehensive
prognostic and predictive evaluation in BC.
Funding
This study was supported by the Research Program
“Development and Validation of Complex Treat-
ment Technology for Breast Cancer Patients of
Young Age” (No. 0122U201203), financed by the
Ministry of Education and Science of Ukraine, and
the Research Program “Stress-Induced Tumor Mi-
croenvironment Factors as Risk Drivers of Breast
Cancer Progression” (No. 0124U000078) funded by
the National Academy of Sciences of Ukraine.
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 39
Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue
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Submitted: March 26, 2026
О. Мартинюк, О. Мушій, А. Павлова
Інститут експериментальної патології, онкології і радіобіології
імені Р.Є. Кавецького НАН України, Київ, Україна
ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ
ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p
ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ
Стан питання. Гетерогенність раку молочної залози (РМЗ) суттєво ускладнює діагностику, прогнозування пе-
ребігу захворювання та передбачення ефективності лікування. МікроРНК розглядаються як перспективні біо-
маркери завдяки їхній участі в регуляції пухлинної прогресії та чутливості до терапії. Водночас комбіноване
клінічне значення циркулюючих і пухлиноасоційованих hsa-miR-26b-5p та hsa-miR-186-5p залишається недо-
статньо вивченим. Матеріали та методи. Досліджено рівні експресії hsa-miR-26b-5p та hsa-miR-186-5p у си-
роватці крові та пухлинній тканині 124 пацієнтів із РМЗ. Проаналізовано їх зв’язок із клініко-патологічними
характеристиками. Прогностичну значущість оцінювали за розвитком прогресії та рецидиву протягом 3 років.
Предиктивну цінність визначали в пацієнтів, які отримували неоад’ювантну хіміотерапію (схема 4AC), із ви-
користанням оцінки відповіді та ROC-аналізу. Результати. У пацієнтів молодого віку (≤ 45 років) виявлено
достовірне зниження рівнів обох мікроРНК у сироватці крові. Експресія hsa-miR-186-5p у сироватці асоцію-
валася зі стадією захворювання, розміром пухлини, статусом лімфатичних вузлів та молекулярним підтипом.
Підвищені рівні циркулюючої hsa-miR-26b-5p були пов’язані з прогресією захворювання, тоді як зниження
hsa-miR-186-5p спостерігалося в пацієнтів із несприятливим перебігом. У пухлинній тканині експресія hsa-
miR-26b-5p корелювала зі ступенем диференціювання, розміром пухлини та наявністю метастазів: її рівні були
підвищені у низькодиференційованих пухлинах та знижені при метастатичному процесі. Натомість hsa-miR-
186-5p була пов’язана з молекулярним підтипом та ураженням лімфатичних вузлів, із найвищими рівнями при
HER2-позитивному РМЗ та в пацієнтів із рецидивом. Підвищені рівні hsa-miR-186-5p у сироватці та пухлин-
ній тканині асоціювалися зі зниженням чутливості до неоад’ювантної хіміотерапії на основі доксорубіцину.
ROC-аналіз підтвердив її високу предиктивну цінність (AUC = 0,750 для сироватки та 0,818 для тканини). Для
hsa-miR-26b-5p такого зв’язку не встановлено. Висновки. hsa-miR-26b-5p та hsa-miR-186-5p відіграють взаємо-
доповнюючі ролі у біології РМЗ. hsa-miR-26b-5p переважно відображає агресивність пухлини та системну про-
гресію, тоді як hsa-miR-186-5p характеризує молекулярні особливості пухлини та чутливість до хіміотерапії. Їх
комбіноване визначення у сироватці крові та пухлинній тканині є перспективним підходом для покращення
прогнозування перебігу захворювання та ефективності лікування.
Ключові слова: рак молочної залози, hsa-miR-26b-5p, hsa-miR-186-5p, доксорубіцин.
|
| id | oai:ojs2.ex.aqua-time.com.ua:article-615 |
| institution | Experimental Oncology |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-06-16T01:00:10Z |
| publishDate | 2026 |
| publisher | PH Akademperiodyka |
| record_format | ojs |
| resource_txt_mv | exp-oncologycomua/d7/7e11c0c36a0e0343df326df6a8b092d7.pdf |
| spelling | oai:ojs2.ex.aqua-time.com.ua:article-6152026-06-15T10:40:17Z Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue Reveals their Prognostic and Predictive Significance in Breast Cancer ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ Martyniuk, О. Mushii, O. Pavlova, A. рак молочної залози, hsa-miR-26b-5p, hsa-miR-186-5p, доксорубіцин breast cancer, hsa-miR-26b-5p, hsa-miR-186-5p, doxorubicin Background. Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clinical signifi ance of circulating and tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insuffi&nbsp;&nbsp; &nbsp;tly elucidated. Materi- als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis- sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic signifi ance was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re- sults. young BC patients (≤45 years) demonstrated signifi antly lower circulating levels of both miRNAs. Serum hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa- miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres- sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub- type and lymph node involvement, with the highest expression observed in hER2-positive tumors and in patients with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confi med its predictive value (AUC = &nbsp;0.750 for serum and 0.818 for tumor tissue). No signifi ant association between hsa-miR-26b-5p and chemothe- rapy response was observed. Conclusions. hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients. Стан питання. Гетерогенність раку молочної залози (РМЗ) суттєво ускладнює діагностику, прогнозування пе- ребігу захворювання та передбачення ефективності лікування. МікроРНК розглядаються як перспективні біо- маркери завдяки їхній участі в регуляції пухлинної прогресії та чутливості до терапії. Водночас комбіноване клінічне значення циркулюючих і пухлиноасоційованих hsa-miR-26b-5p та hsa-miR-186-5p залишається недо- статньо вивченим. Матеріали та методи. Досліджено рівні експресії hsa-miR-26b-5p та hsa-miR-186-5p у си- роватці крові та пухлинній тканині 124 пацієнтів із РМЗ. Проаналізовано їх зв’язок із клініко-патологічними характеристиками. Прогностичну значущість оцінювали за розвитком прогресії та рецидиву протягом 3 років. Предиктивну цінність визначали в пацієнтів, які отримували неоад’ювантну хіміотерапію (схема 4AC), із ви- користанням оцінки відповіді та ROC-аналізу. Результати. У пацієнтів молодого віку (≤ 45 років) виявлено достовірне зниження рівнів обох мікроРНК у сироватці крові. Експресія hsa-miR-186-5p у сироватці асоцію- валася зі стадією захворювання, розміром пухлини, статусом лімфатичних вузлів та молекулярним підтипом. Підвищені рівні циркулюючої hsa-miR-26b-5p були пов’язані з прогресією захворювання, тоді як зниження hsa-miR-186-5p спостерігалося в пацієнтів із несприятливим перебігом. У пухлинній тканині експресія hsa- miR-26b-5p корелювала зі ступенем диференціювання, розміром пухлини та наявністю метастазів: її рівні були підвищені у низькодиференційованих пухлинах та знижені при метастатичному процесі. Натомість hsa-miR- 186-5p була пов’язана з молекулярним підтипом та ураженням лімфатичних вузлів, із найвищими рівнями при hER2-позитивному РМЗ та в пацієнтів із рецидивом. Підвищені рівні hsa-miR-186-5p у сироватці та пухлин- ній тканині асоціювалися зі зниженням чутливості до неоад’ювантної хіміотерапії на основі доксорубіцину. ROC-аналіз підтвердив її високу предиктивну цінність (AUC = 0,750 для сироватки та 0,818 для тканини). Для hsa-miR-26b-5p такого зв’язку не встановлено. Висновки. hsa-miR-26b-5p та hsa-miR-186-5p відіграють взаємо- доповнюючі ролі у біології РМЗ. hsa-miR-26b-5p переважно відображає агресивність пухлини та системну про- гресію, тоді як hsa-miR-186-5p характеризує молекулярні особливості пухлини та чутливість до хіміотерапії. Їх комбіноване визначення у сироватці крові та пухлинній тканині є перспективним підходом для покращення прогнозування перебігу захворювання та ефективності лікування. PH Akademperiodyka 2026-06-14 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/615 10.15407/exp-oncology.2026.01.031 Experimental Oncology; Vol. 48 No. 1 (2026): Experimental Oncology; 31-39 Експериментальна онкологія; Том 48 № 1 (2026): Експериментальна онкологія; 31-39 2312-8852 1812-9269 10.15407/exp-oncology.2026.01 en https://exp-oncology.com.ua/index.php/Exp/article/view/615/460 Copyright (c) 2026 Experimental Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | рак молочної залози hsa-miR-26b-5p hsa-miR-186-5p доксорубіцин Martyniuk, О. Mushii, O. Pavlova, A. ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title | ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title_alt | Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue Reveals their Prognostic and Predictive Significance in Breast Cancer |
| title_full | ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title_fullStr | ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title_full_unstemmed | ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title_short | ПРОГНОСТИЧНЕ ТА ПРЕДИКТИВНЕ ЗНАЧЕННЯ ЦИРКУЛЮЮЧИХ ТА ПУХЛИНО-АСОЦІЙОВАНИХ hsa-miR-26b-5p ТА hsa-miR-186-5p ПРИ РАКУ МОЛОЧНОЇ ЗАЛОЗИ |
| title_sort | прогностичне та предиктивне значення циркулюючих та пухлино-асоційованих hsa-mir-26b-5p та hsa-mir-186-5p при раку молочної залози |
| topic | рак молочної залози hsa-miR-26b-5p hsa-miR-186-5p доксорубіцин |
| topic_facet | рак молочної залози hsa-miR-26b-5p hsa-miR-186-5p доксорубіцин breast cancer hsa-miR-26b-5p hsa-miR-186-5p doxorubicin |
| url | https://exp-oncology.com.ua/index.php/Exp/article/view/615 |
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