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A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder.
Dis Markers. 2018; 2018:5468672.DM

Abstract

INTRODUCTION AND OBJECTIVES

MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs 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 nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB.

METHODS

To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB 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, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive 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 UCB patients were 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 UCB.

Links

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Authors+Show Affiliations

Inamoto T
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Uehara H
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Akao Y
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Ibuki N
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Komura K
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Takahara K
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Takai T
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Uchimoto T
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Saito K
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Tanda N
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Yoshikawa Y
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Minami K
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Hirano H
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Nomi H
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.
Kato R
Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Hayashi T
Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Azuma H
Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.

MeSH

AgedAged, 80 and overBiomarkers, TumorCarcinomaHumansMaleMicroRNAsSurvival AnalysisTranscriptomeUrinary Bladder NeoplasmsUrothelium

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30026881

Citation

Inamoto, Teruo, et al. "A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients With Urothelial Carcinoma of the Bladder." Disease Markers, vol. 2018, 2018, p. 5468672.
Inamoto T, Uehara H, Akao Y, et al. A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder. Dis Markers. 2018;2018:5468672.
Inamoto, T., Uehara, H., Akao, Y., Ibuki, N., Komura, K., Takahara, K., Takai, T., Uchimoto, T., Saito, K., Tanda, N., Yoshikawa, Y., Minami, K., Hirano, H., Nomi, H., Kato, R., Hayashi, T., & Azuma, H. (2018). A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder. Disease Markers, 2018, 5468672. https://doi.org/10.1155/2018/5468672
Inamoto T, et al. A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients With Urothelial Carcinoma of the Bladder. Dis Markers. 2018;2018:5468672. PubMed PMID: 30026881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder. AU - Inamoto,Teruo, AU - Uehara,Hirofumi, AU - Akao,Yukihiro, AU - Ibuki,Naokazu, AU - Komura,Kazumasa, AU - Takahara,Kiyoshi, AU - Takai,Tomoaki, AU - Uchimoto,Taizo, AU - Saito,Kenkichi, AU - Tanda,Naoki, AU - Yoshikawa,Yuki, AU - Minami,Koichiro, AU - Hirano,Hajime, AU - Nomi,Hayahito, AU - Kato,Ryuji, AU - Hayashi,Tetsuya, AU - Azuma,Haruhito, Y1 - 2018/06/20/ PY - 2017/12/16/received PY - 2018/5/7/accepted PY - 2018/7/21/entrez PY - 2018/7/22/pubmed PY - 2018/10/30/medline SP - 5468672 EP - 5468672 JF - Disease markers JO - Dis Markers VL - 2018 N2 - INTRODUCTION AND OBJECTIVES: MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs 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 nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. METHODS: To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB 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, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive 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 UCB patients were 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 UCB. SN - 1875-8630 UR - https://www.unboundmedicine.com/medline/citation/30026881/A_Panel_of_MicroRNA_Signature_as_a_Tool_for_Predicting_Survival_of_Patients_with_Urothelial_Carcinoma_of_the_Bladder_ DB - PRIME DP - Unbound Medicine ER -