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Differential Gene Expression for ccRCC Tumors with Varied Clinical Outcomes
Molly J. Parries, MD, Kailey Hooper, BS, Eric Burks, MD, Travis Sullivan, MS, Kimberly Rieger-Christ, PhD.
Lahey Hospital and Medical Center, Burlington, MA, USA.
BACKGROUND Clear cell (ccRCC) is the most common subtype of renal cell carcinoma. The five-year relative survival across all stages is 50-69%, with worse outcomes for larger, higher stage tumors. Earlier detection may improve survival.
METHODS We performed a retrospective cohort study using our institution's prospectively maintained biorepository. ccRCC patients with ≥ one year of follow up were included. A “good outcomes” (GO) group had no recurrence over the follow up period, whereas a “poor outcomes” (PO) group had recurrence with or without disease-specific mortality. RNA was isolated from frozen tumor samples followed by RNA sequencing and differential gene expression (DGE) analysis.
RESULTS Fourteen (14) samples were included in the GO group and 10 in the PO group. Groups had similar average tumor size (GO 6.9cm vs PO 7.4cm, p = 0.93), age at diagnosis (GO 61.4 vs PO 60.1, p = 0.75), and average follow up duration (GO 6.4 vs PO 6.6 years, p = 0.95). Proportion of high stage (T3) tumors was 28.5% for GO vs 50% for PO (Fisher's exact test, p = 0.4). We identified 537 DGEs (FDR<0.05, |fold change|>2) between groups. Gene ontology demonstrated upregulation of genes related to epithelial-mesenchymal transition (EMT) and immune response in the PO group. KEGG analysis showed enrichment of immune-related pathways, including complement cascade and autoimmune disease. EMT, cytokine signaling, and inflammatory response pathways were upregulated on GSEA hallmark analysis.
CONCLUSIONS These data provide long-term, disease-specific outcomes and DGE between patients with durable remission and those with poor outcomes, adding specificity to existing five-year survival data. RNA sequencing demonstrated upregulation of genes involved in immune response and EMT in the group with worse outcomes, suggesting these pathways may be useful biomarkers for aggressive tumors. Future work will evaluate candidate oncogenes as potential biomarkers for ccRCC.
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