Abstract: PD62-10
Sources of Funding: None

Introduction

Although survival benefit of cisplatin-based neoadjuvant chemotherapy for muscle-invasive bladder cancer has been demonstrated, a significant proportion of patients do not respond. Identification of chemoresponsive cohorts would avoid morbidity and prevent delayed surgical intervention in patients who are unlikely to benefit. We evaluate the role of miRNA and mRNA expression profiles in initial TURBT specimens of patients who receive neoadjuvant chemotherapy prior to radical cystectomy. Differences in TURBT specimen expression patterns between complete responders (pT0) and nonresponders (pT2≤) at time of cystectomy may help stratify patients for possible neoadjuvant chemotherapy.

Methods

FFPE tissue was isolated from initial TURBT specimens of patients with clinically localized MIBC treated with cisplatin-based neoadjuvant chemotherapy. Tissue from 9 patients with T2≤ disease was compared with samples from 10 pT0 patients at time of cystectomy. Differential expression of 754 miRNAs and mRNA was analyzed utilizing RT-qPCR. miRNA expression profiles were compared between complete responders and nonresponders. mRNA in tumor specimens was sequenced from both groups with 76 base pair paired-end reads using NextSeq technology. KEGG Pathway analyses were used to identify differential gene expression patterns between the two groups.

Results

Significant upregulation of miRNA 485-3p, miRNA 520d, miRNA 410, miRNA 872, and miRNA 1304 was observed in nonresponders versus complete responders. KEGG pathway analysis revealed significant upregulation of the hsa03430 pathway, implicated in DNA mismatch repair, the hsa03420 pathway, implicated in nucleotide excision repair, and the hsa03410 pathway, involved in base excision repair, among pT0 patients.

Conclusions

Differential miRNA and mRNA expression within the initial tumor specimen of patients with complete pathologic regression versus progression indicates a possible role in determining-neoadjuvant chemo-sensitivity. Upregulation of DNA repair mechanisms in the primary tumor may signify chemo-sensitivity and help stratify MIBC patients being considered for neoadjuvant chemotherapy.

Funding

None