Chromophobe renal cell carcinoma (chRCC) is known as an indolent tumor; however, mortality still occurs. We sought to determine the clinicopathologic and genomic factors associated with aggressive chRCC.
Two different datasets were used to identify patients with clinical stage III and IV chRCC. Eighteen patients from The Cancer Genome Atlas (TCGA) database and 1693 patients from the American College of Surgeons National Cancer Database (NCDB) were used for analysis. From the TCGA, RNA-Seq expression analysis of 18,745 genes was conducted between the recurrent (n = 5; 27.8%) and nonrecurrent patients (n = 13; 72.2%). Biological significance was identified via pathway enrichment and gene function analyses. From the NCDB, Cox proportion hazards regression models were used to identify variables associated with overall survival (OS) at a median follow-up of 41.4 months.
Between the 2 groups, 2182 genes were differentially expressed. The most commonly overexpressed pathways were neuroactive ligand-receptor interactions and cytokine-cytokine receptor interactions. The most activated gene functions were cellular, metabolic, and multicellular organismal processes. In the NCDB, multivariable analysis, age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < .001), TNM stage IV versus III (HR, 3.86; 95% CI, 2.98-5.00; P < .001), and positive surgical margin (HR, 1.68; 95% CI, 1.45-1.96; P < .001) were associated with worse OS at a median follow-up of 41.4 months. Five-year OS was significantly lower for stage IV patients compared with stage III patients (80.0% vs. 29.9%; P < .001).
Patients with recurrent chRCC demonstrated a differential gene expression of specific biochemical pathways. Clinical parameters associated with worse OS included age, stage, and positive surgical margin.
Clinical genitourinary cancer. 2018 Dec 08 [Epub ahead of print]
Alp Tuna Beksac, Mesude Bicak, Ishan Paranjpe, David J Paulucci, John P Sfakianos, Ketan K Badani
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY., Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: .