Diagnostic miRNA Signatures in Paired Tumor, Plasma, and Urine Specimens From Renal Cell Carcinoma Patients.

Publication Title

Clinical chemistry

Authors

Matias A Bustos, Department of Translational Molecular Medicine, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United StatesFollow
Josh Gottlieb, Department of Urologic Oncology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United StatesFollow
Jane Choe, Department of Urologic Oncology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States
Suyeon Ryu, Department of Genomic Sequencing Center, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow
Selena Y Lin
Warren M Allen, Department of Surgical Pathology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow
David L Krasne, Department of Surgical Pathology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow
Timothy G Wilson, Department of Urologic Oncology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow
Dave S B Hoon, Department of Translational Molecular Medicine, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Department of Genomic Sequencing Center, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow
Jennifer M Linehan, Department of Urologic Oncology, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.Follow

Document Type

Article

Publication Date

10-4-2023

Keywords

california; sjci; genomics

Abstract

BACKGROUND: The incidence of patients diagnosed with renal cell carcinoma (RCC) is increasing. There are no approved biofluid biomarkers for routine diagnosis of RCC patients. This retrospective study aims to identify cell-free microRNA (cfmiR) signatures in urine samples that can be utilized as biomarkers for early diagnosis of sporadic RCC patients.

METHODS: Tissue, plasma, and urine samples (n = 221) from 56 sporadic RCC patients and respective normal healthy donors were profiled for 2083 microRNAs (miRs) using the next-generation sequencing-based HTG EdgeSeq miR Whole Transcriptome Assay. DESeq2 (FC |1.2|, false discovery rate

RESULTS: We found a 10-miR signature that distinguished RCC tissues from remote normal kidney tissue or benign kidney lesion samples. Additionally, we identified subtype-specific miRs (miR-122-5p, miR-210-3p, and miR-21-3p) and miRs specific for all RCC subtypes (miR-106b-3p, miR-629-5p, and miR-885-5p). We observed that miR-155-5p was associated with tumor size. Using The Cancer Genome Atlas data sets, we validated the miRs found in RCC tissue samples. In plasma or urine analysis, we found cfmiRs that were consistently and significantly upregulated in RCC tissue samples. A 15-cfmiR signature was proposed in urine samples of RCC patients, of which miR-1275 was consistently upregulated in tissue, plasma, and urine samples.

CONCLUSIONS: This integrative study found diagnostic miRs/cfmiRs for RCC patients, which were validated using The Cancer Genome Atlas data sets. Distinctive cfmiR signatures found in urine may have clinical utility for the diagnosis of RCC.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

DOI

10.1093/clinchem/hvad133

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