Association between TOP2A, RRM1, HER2, ERCC1 expression and response to chemotherapy in patients with non-muscle invasive bladder cancer

Abstract

PurposeThis study aimed to detect the expression levels of topoisomerase IIα (TOP2A), ribonucleotide reductase catalytic subunit M1 (RRM1),c-erbB-2 (HER2) and excision repair cross complementing group 1 (ERCC1) in non-muscular invasive bladder cancer (NMIBC) and explore the correlation between the expression of these genes and NMBIC sensitivity to pirarubicin or gemcitabine treatment. Materials and methodsNMIBC patient tissues and the bladder cancer cell lines BIU-87 and KK47 were selected for the exploration of drug sensitivity in vitro. Immunohistochemistry was used to examine protein expression in tissues. Reverse transcription-polymerase chain reaction (RT-qPCR) and a Western blot assay were used to detect the mRNA and protein levels in cells. The cell IC50 value was evaluated by an MTT assay. Flow cytometry was used to sort the cell subpopulations. ResultsIn the pirarubicin-treated group, the patients with high TOP2A expression experienced lower recurrence rates than those with low TOP2A expression, whereas TOP2A and HER2 co-expression resulted in higher recurrence rates. The patients with low RRM1 expression, especially those with low ERCC1 expression, experienced lower recurrence rates than the patients with high RRM1 expression in the gemcitabine-treated group. Tumour cells with high TOP2A expression were highly sensitive to pirarubicin, and TOP2A+ HER2- cells were more sensitive to pirarubicin than TOP2A+ HER2+ cells. Cells with low RRM1 expression levels were sensitive to gemcitabine, and RRM1−ERCC1- cells were more sensitive to gemcitabine than RRM1−ERCC1+ cells. ConclusionHigh TOP2A expression or low RRM1 expression could predict the sensitivity of NMIBC to pirarubicin or gemcitabine treatment. HER2 and ERCC1 expression may affect the effect of TOP2A and RRM1, thus affecting the efficacy of chemotherapeutic drugs.