Cell Cycle Proliferation and Epithelial-Mesenchymal Transition Pathway Scores Predictive of Recurrence and Survival for ccRCC

Cell cycle proliferation (CCP) and epithelial-mesenchymal transition (EMT) pathway scores were found to significantly identify patients who were going to develop disease recurrence and die from clear cell renal cell carcinoma (ccRCC), according to results from a poster presented at the 2021 International Kidney Cancer Symposium: North America.

Over-expression of Wilms tumor 1 (WT1) and CCP genes were observed in the discovery cohort in paired tumor thrombus compared with the primary tumor, and among patients with recurrence versus those without recurrence. The enrichment of EMT- and CCP-related pathways was observed among patients with a high WT1 expression in the TCGA validation ccRCC cohort, according to findings from a hallmark pathway analysis. Using the validation cohort CCP and EMT scores, investigators were able to stratify patients into 4 risk groups utilizing Youden-Index cut points. The groups included CCP^low/EMT^low, CCP^high/EMT^low, CCP^low/EMT^high, and CCP^high/EMT^high.

“We demonstrate the synergistic prognostic impact of EMT in tumors with high CCP score. Our novel EMT score has the potential to improve risk stratification and provide potential novel therapeutic targets,” the investigators wrote.

Patients with ccRCC were retrospectively analyzed in 2 cohorts, including those who underwent a radical nephrectomy (RNx) with inferior vena cava (IVC) tumor thrombectomy (n = 5) and those who underwent RNx for localized disease and developed recurrence compared with no recurrence (n = 36). The research team utilized samples from The Cancer Genome Atlas (TCGA) Research Network ccRCC cohort to validate results (n = 386). Kaplan-Meier and multivariable cox-proportional hazard testing were implemented to analyze the prognostic ability of CCP and EMT pathway scores on patient progression-free survival (PFS) and disease-specific survival (DSS).

Investigators identified an association between the CCP^high/EMT^high risk group and the worst PFS (P < .001) and DSS (P < .001) outcomes. The group was also independently associated with poor PFS (HR, 4.6) and DSS (HR, 10.3; P < .001) outcomes, according to a multivariable analysis.

Other findings from a differential expression and pathway analysis of TCGA high and low WT1 tumors identified that the EMT pathway could be the top enriched pathway for those with high WT1 tumors.

“There is an ongoing need to develop prognostic biomarkers to improve the management of clear cell carcinoma,” the investigators wrote in their poster. “Our novel EMT score has the potential to improve risk stratification and provide potential novel therapeutic targets.”

Reference

Nallandhighal S, Vince R, Karim R, et al. Molecular dissection of clear cell renal cell carcinoma reveals prognostic significance of epithelial-mesenchymal transition gene expression signature. Presented at 2021 International Kidney Cancer Symposium North America; November 5-6, 2021. Abstract LBA47