Whole-transcriptome sequencing identified gene expression signatures associated with aggressive clear cell renal cell carcinoma

Ken Batai, Elliot Imler, Jayce Pangilinan, Robert Bell, Aye Lwin, Elinora Price, Tijana Milinic, Amit Arora, Nathan A. Ellis, Erika Bracamonte, Bruce Seligmann, Benjamin R. Lee

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalGenes and Cancer
Volume9
Issue number5-6
DOIs
Publication statusPublished - May 1 2018

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Keywords

  • Biomarkers
  • Hispanic americans
  • Kidney cancer
  • Molecular subtype
  • Whole transcriptome sequencing

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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