Vol.:(0123456789) 1 3
Molecular Biology Reports
https://doi.org/10.1007/s11033-020-05932-3
ORIGINAL ARTICLE
Uncovering the expression patterns and the clinical significance
of miR‑182, miR‑205, miR‑27a and miR‑369 in patients with urinary
bladder cancer
Nouha Setti Boubaker
1,5
· Aymone Gurtner
5,6
· Nesrine Trabelsi
1
· Isabella Manni
5
· Haroun Ayed
1,2
·
Ahmed Saadi
1,2
· Zeineb Naimi
3
· Meriem Ksontini
4
· Mouna Ayadi
3
· Ahlem Blel
4
· Soumaya Rammeh
4
·
Mohamed Chebil
2
· Giulia Piaggio
5
· Slah Ouerhani
1
Received: 19 August 2020 / Accepted: 17 October 2020
© Springer Nature B.V. 2020
Abstract
Background Given the high recurrence and progression rates and the absence of reliable markers for early detection and
prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity
is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the
expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa.
Methods and results The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44
HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed
using 2
−ΔΔCT
method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and
the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a,
miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001).
MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the
distribution of miR-27a’s expression among these tumor groups was almost significant (p = 0.05) and that of miR-369’s
expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC
(p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression
in NMIBC patients (p = 0.01).
Conclusion Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diag-
nostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was high-
lighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory
to strengthen these findings.
Keywords Epigenetic · MicroRNA · Bladder cancer · Expression profiles · Diagnosis · Prognosis
Introduction
According to the Global Cancer Observatory (GLOBOCAN)
database, Bladder cancer (BCa) is the 10th most frequent
detected cancer and 9th most lethal malignancy in men [1].
It is the most frequent urological cancer in men in Tunisia
[2]. At the time of diagnosis, 75% of diagnosed BCa cases
are localized in the mucosa or the submucosa (non-muscle-
invasive bladder cancer NMIBC), characterized by papil-
lary and multifocal aspect, occasionally progress to invasive
disease and have an acceptable prognosis once treated at an
early stage. Whereas in 25% of situations, tumor cells have
already infiltrated the muscle (muscle-invasive bladder can-
cer MIBC), arise as nodular or metastasizes neoplasm in the
early phases with a very poor prognosis [3, 4]. Early detec-
tion and monitoring are essential for a better clinical out-
come of BCa patients (disease recurrence and progression).
At present, commonly used diagnosis strategies are cys-
toscopy with endoscopic tumor resection and cytology.
* Nouha Setti Boubaker
nouha.setti@hotmail.fr
* Giulia Piaggio
giulia.piaggio@ifo.gov.it
Extended author information available on the last page of the article