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Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers

1
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea
2
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD 21287, USA
3
Department of Oncology, Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University of Medicine, Baltimore, MD 21287, USA
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Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul 02447, Korea
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Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02447, Korea
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Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Korea
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 222; https://doi.org/10.3390/cancers12010222
Received: 23 December 2019 / Revised: 14 January 2020 / Accepted: 15 January 2020 / Published: 16 January 2020
The molecular characteristics of early-stage clear cell renal cell carcinomas (ccRCCs) measuring ≤7 cm associated with poor clinical outcomes remain poorly understood. Here, we sought to validate genes associated with ccRCC progression and identify candidate genes to predict ccRCC aggressiveness. From among 1069 nephrectomies performed on patients, RNA sequencing was performed for 12 ccRCC patients with aggressive characteristics and matched pairs of 12 ccRCC patients without aggressive characteristics. Using a prospective cohort (ClinicalTrials.gov Identifier: NCT03694912), the expression levels of nine genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, and BAIAP2L1) were measured by reverse-transcription polymerase chain reaction from frozen tissues, and their relation to Fuhrman grade was investigated in 70 patients with small ccRCC (≤4 cm). In total, 251 genes were differentially expressed and presented fold changes with p-values < 0.05; moreover, 10 genes with the greatest upregulation or downregulation in aggressive ccRCC remained significant even after adjustment. We validated previously identified genes that were associated with ccRCC progression and identified new candidate genes that reflected the aggressiveness of ccRCC. Our study provides new insight into the tumor biology of ccRCC and will help stratify patients with early-stage ccRCC by molecular subtyping. View Full-Text
Keywords: clear cell renal cell carcinomas; RNA sequencing; gene expression analysis; prognostic biomarkers clear cell renal cell carcinomas; RNA sequencing; gene expression analysis; prognostic biomarkers
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Park, J.S.; Pierorazio, P.M.; Lee, J.H.; Lee, H.J.; Lim, Y.S.; Jang, W.S.; Kim, J.; Lee, S.H.; Rha, K.H.; Cho, N.H.; Ham, W.S. Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers. Cancers 2020, 12, 222.

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