Whole-transcriptome sequencing identified gene expression signatures associated with aggressive clear cell renal cell carcinoma
Ken Batai1, Elliot Imler2, Jayce Pangilinan1, Robert Bell3, Aye Lwin1, Elinora Price4, Tijana Milinic1, Amit Arora5, Nathan A. Ellis6, Erika Bracamonte3, Bruce Seligmann2 and Benjamin R. Lee1
1 Division of Urology, Department of Surgery, University of Arizona, Tucson, AZ, USA
2 BioSpyder Technologies, Inc, Tucson, AZ, USA
3 Department of Pathology, University of Arizona, Tucson, AZ, USA
4 Department of Surgery, University of Arizona, Tucson, AZ, USA
5 Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
6 Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA
Correspondence:
Ken Batai, email:
Keywords: kidney cancer; biomarkers; molecular subtype; Hispanic Americans; whole transcriptome sequencing
Received: September 24, 2018 Accepted: October 31, 2018 Published: Novembr 11, 2018
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer, yet molecular biomarkers have not been used for the prognosis of ccRCC to aide clinical decision making. This study aimed to identify genes associated with ccRCC aggressiveness and overall survival (OS). Samples of ccRCC tumor tissue were obtained from 33 patients who underwent nephrectomy. Gene expression was determined using whole-transcriptome sequencing. The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) RNA-seq data was used to test association with OS. 290 genes were differentially expressed between tumors with high and low stage, size, grade, and necrosis (SSIGN) score (≥7 vs. ≤3) with PADJ<0.05. Four genes, G6PD, APLP1, GCNT3, and PLPP2, were also over-expressed in advanced stage (III and IV) and high grade (3 and 4) ccRCC and tumor with necrosis (PADJ<0.05). Investigation stratifying by stage found that APLP1 and PLPP2 overexpression were significantly associated with poorer OS in the early stage (Quartile 1 vs. Quartile 4, HR = 3.87, 95% CI:1.25-11.97, P = 0.02 and HR = 4.77, 95% CI:1.37-16.57, P = 0.04 respectively). These genes are potential biomarkers of ccRCC aggressiveness and prognosis that direct clinical and surgical management.
