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Am J Pathol. 2018 Nov;188(11):2487-2496. doi: 10.1016/j.ajpath.2018.07.026. Epub 2018 Sep 8.

Global and Targeted miRNA Expression Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links miR-155-5p and miR-210-3p to both Tumorigenesis and Recurrence.

Author information

1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, China.
2
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, China; Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer, Fourth Military Medical University, Xi'an, China.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: xwu@mdanderson.org.

Abstract

About 30% of patients undergoing nephrectomy for renal cell carcinoma (RCC) experience disease recurrence. We profiled miRNAs dysregulated in clear-cell (cc) RCC tumor tissues and predictive of recurrence. The expression levels of 800 miRNAs were assessed in paired tumor and normal tissues from a discovery cohort of 18 ccRCC patients. miRNAs found to be differentially expressed were examined in a validation set of 205 patients, using real-time quantitative PCR. Tumor-normal data from 64 patients in The Cancer Genome Atlas were used for external validation. Twenty-eight miRNAs were consistently dysregulated in tumor tissues. On dichotomized analysis, patients with high levels of miR-155-5p and miR-210-3p displayed an increased risk for ccRCC recurrence (hazard ratio, 2.64; 95% CI, 1.49 to 4.70; P = 0.0009; and hazard ratio, 1.80; 95% CI, 1.04 to 3.12; P = 0.036, respectively) and a shorter median recurrence-free survival time than did patients with low levels [P < 0.01 (log rank test)]. A risk score was generated based on the expression levels of miR-155-5p and miR-210-3p, and the trend test was significant (P = 0.005). On pathway analysis, target genes regulated by miR-155-5p and miR-210-3p were mainly enriched in inflammation-related pathways. We identified and validated multiple miRNAs dysregulated in ccRCC tissues; miR-155-5p and miR-210-3p were predictive of ccRCC recurrence, pointing to potential utility as biomarkers and underlying biological mechanisms.

PMID:
30201497
PMCID:
PMC6207099
[Available on 2019-11-01]
DOI:
10.1016/j.ajpath.2018.07.026

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