Abstract
Background
Till now, no definite clinical or laboratory marker can predict the recurrence or
progression of T1 G3 urothelial carcinoma (UC). Genetic aberrations of the chromatin
remodeling genes and sister chromatid cohesion and segregation (SCCS) were identified
in UC. Here we investigated the impact of novel miRNAs and their targeted expressed
SCCS and chromatin remodeling genes on T1G3 UC response to Bacillus Calmette-Guérin
(BCG) therapy.
Methods
One hundred tissue samples were obtained from NMIBC patients. Gene expression and
immunohistochemical assay of STAG2, ARID1A, NCOR1and UTX were assessed. MiRNA analysis
for their targeting miRNAs (miR-21, miR-31, Let7a and miR-199a) was carried out. Assessed
genes were compared between responders and no responders to BCG. Univariate and multivariate
analysis of predictors of disease recurrence and progression were performed using
cox regression analysis.
Results
Thirty-two and 22 patients developed recurrence and progression to MIBC (BCG non-responders).
BCG non-responders showed statistically significant higher expression of miR-21 and
their targeted STAG2, miR-199a and NCOR1 gene (P < .001), and lower expression of miR-31, Let7a, ARID1A and UTX genes (P < .001). Higher miR-199a (P = .006) and lower miR-31 (P = .01), ARID1A (P = .008) and UTX (P = .03) were independent predictor of higher tumor recurrence. Recurrent disease (P = .003), higher expression of STAG2 (P = .01), NCOR1 (P = .01) and miR-21 (P = .03) genes and lower expression of miR-31 (P = .02), Let7a (P = .04) and ARID1A (P = .04) genes were the independent predictor of disease progression.
Conclusion
Upregulation of STAG2 and NCOR1 and down regulation of ARID1A and UTX genes and their
targeting miRNAs were associated with UC non-response to BCG.
Keywords
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Article info
Publication history
Published online: December 16, 2021
Accepted:
December 4,
2021
Received in revised form:
November 29,
2021
Received:
July 29,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
