Gene-expression signature could serve as biomarker for recurrence in ccRCC

Investigators have developed and validated a 15-gene prognostic signature that was shown to be independently associated with worse disease-free survival (DFS) and disease-specific survival (DSS) in patients with clear cell renal cell carcinoma (ccRCC), showing potential value as a biomarker for disease recurrence in these patients.^1,2

In the validation A cohort, the gene signature also demonstrated an association with worse DFS and DSS.

Data from the study were published in JCO Precision Oncology.¹

“We’ve developed a 15-gene signature that can risk-stratify patients with clear cell renal cancer from low to high,” senior author Simpa S. Salami, MD, MPH, associate professor of urology at Michigan Medicine, said in a news release on the findings.² “Even when we adjusted for other clinical variables, like age or grade of tumor, this signature was still independently associated with recurrence after treatment for this form of kidney cancer.”

For the study, the investigators retrospectively identified patients who had undergone radical nephrectomy for ccRCC and had follow-up after surgery for inclusion in the discovery cohort. In total, 50 patients who experienced disease recurrence and 41 patients who did not were included for analysis. Patients with disease recurrence were matched on the basis of grade/stage of disease to those who did not experience recurrence. The median follow-up was 26 months and 36 months for these patients, respectively.

Overall, the 15-gene signature was found to be independently associated with worse DFS (HR, 11.08; 95% CI, 4.9-25.1) and DSS (HR, 9.67; 95% CI, 3.4-27.7) even after adjusting for the 31-gene cell cycle progression (mxCCP) score and clinicopathologic factors such as stage, size, grade, necrosis score, and Memorial Sloan Kettering Cancer Center nomogram.

The signature was then assessed in 2 validation cohorts, which included a total of 761 patients. In the validation A cohort (n = 382), the gene signature also demonstrated an association with worse DFS (HR, 2.6; 95% CI, 1.6-4.3) and DSS (HR, 3; 95% CI, 1.4-6.1] after adjustments were made for mxCCP score and clinicopathologic variables. A similar trend was again seen in the validation B cohort (n =379), with the signature showing an association with worse DFS (HR, 2.1; 95% CI, 1.2-3.6] and overall survival (HR, 3; 95% CI, 1.6-5.7) following adjustments.

Based on these findings, the authors wrote, “Pending further validation, this signature has the potential to facilitate optimal treatment allocation.”¹

Salami also believes that this signature holds potential across different areas of kidney cancer management. He added in the news release,² “There's potential for using this signature to identify patients who should receive low versus high intensity surveillance. It could inform how frequently to do surveillance imaging after initial treatment and, if validated, may be used to guide the selection of patients for additional systemic treatment after surgery.”

However, according to the news release, more research is needed to assess the impact of the gene signature findings on clinical decision-making.²

References

1. Mehra R, Nallandhighal S, Cotta B, et al. Discovery and validation of a 15-gene prognostic signature for clear cell renal cell carcinoma. JCO Precis Oncol. 2024 May:8:e2300565. doi:10.1200/PO.23.00565

2. Researchers identify a novel biomarker linked to renal cancer recurrence. News release. Michigan Medicine – University of Michigan. June 25, 2024. Accessed June 26, 2024. https://www.newswise.com/articles/researchers-identify-a-novel-biomarker-linked-to-renal-cancer-recurrence