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A panel of micro-RNA signature as a tool for predicting survival of patients with urothelial carcinoma of the bladder

Login to Access Video or Poster Abstract: MP10-08
Sources of Funding: none

Introduction

Micro-RNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal non-aggressive counterpart using miRNA expression levels, and to assess the prognostic value of this specific miRNA markers in patients with UBC.

Methods

To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UBC, miRNA expression was profiled in patients&[prime] samples with an aggressive phenotype or non-aggressive phenotype using 3D-Gene miRNA labeling kit (Toray, JAPAN). To create a prognostic index model, we used the panel of 9-miRNAs signature based on Cancer Genome Atlas (TCGA) data portal [TCGA Data Portal [https://tcga data.nci.nih.gov/tcga/tcgaHome2.jsp]]. MiRNA expression data and corresponding clinical data, including outcome and staging information of 84 UBC patients were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups.

Results

Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, hsa-miR-33b-3p) was determined in a UBC patients with aggressive phenotype compared with non-aggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA BCa patients, ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0.001).

Conclusions

The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UBC.

Funding

none

Authors
Teruo Inamoto
Kiyoshi Takahara
Naokazu Ibuki
Tomoaki Takai
Taizo Uchimoto
Kenkichi Saito
Naoki Tanda
Yuki Yoshikawa
Koichiro Minami
Hajime Hirano
Hayahito Nomi
Haruhito Azuma
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