An Intricate Relationship Between miR-155-5p Expression and OxidativeStress in Bladder Cancer Patients Treated with Calmette-GuerinImmunotherapy

Document Type : Original Article

Authors
1 Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
2 Department of Urology, Hashemi Nejad Kidney Center (HKC), Iran University of Medical Sciences (IUMS), Tehran, Iran.
3 Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
4 Pasteur Institute of Iran, Tehran, Iran.
5 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
6 Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
7 Clinical Research Development Center, Shahid Beheshti Hospital,Babol University of M7. Clinical Research Development Center, Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Iran.edical Sciences, Babol, Iran.
8 Department of Urology, School of Medicine, Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Iran.
Abstract
Treatment failure after intravesical instillation of Bacillus Calmette-Guerin immunotherapy (BCG) for non-
muscle-invasive bladder cancer (BCa) occurs frequently. The exact effects of BCG on cellular redox status and
gene expression remain unclear. We assessed oxidative stress biomarkers and changes in miR-155-5p expression
in response to BCG. Twenty-seven patients with BCa were recruited for measuring tissue and serum
malondialdehyde (MDA) and total antioxidant capacity (TAC) levels, and tissue expression of miR-155-5p at
two-time points: pre and 6 weeks post BCG. Recurrence of BCa was observed after 20 months. R statistical
software was used for paired comparisons of biomarkers, as well as the correlation between variables. Significant
increases in TAC were observed after BCG (P= <0.001). Tissue MDA levels were significantly reduced (P=
0.003). miR-155-5p was slightly overexpressed after BCG (median fold change=1.3, P=0.25). At the 20-month
follow-up, it was observed that improved MDA and TAC changes were significant only in patients without
recurrence of BCa. In patients with recurrence, the pre-treatment expression ratio of miR-155-p5 was positively
correlated with TAC (R=0.63, P= 0.032) and negatively correlated with MDA (R=-0.72, P=0.037). In patients
with recurrence of BCa pre-treatment miR-155-5p showed negative correlation with its expression changes after
BCG (R=-0.78, P=0.004). Conclusions: Treatment with BCG has some beneficial effects on the oxidative stress
status, which is probably modulated by miR-155-5p. A well-controlled oxidative balance may enhance overall
survival of BCa. Considering its high recurrence rate, our pilot experiment can open a window toward better
management of patients with BCa.
Keywords