Adjuvant immune checkpoint inhibitor trials in renal cell carcinoma (RCC) call for improved recurrence risk stratification. Due to limitations of circulating tumor DNA (ctDNA) use in RCC, the use of hypermethylated SHOX2 gene (mSHOX2) in circulating cell-free DNA is explored as a surrogate marker for identifying high-risk patients after RCC surgery.
Liquid biopsies were collected post-surgery from 45 RCC patients (mean duration 4.3 days). Real-time polymerase chain reaction was used to analyze SHOX2 methylation in circulating cell-free DNA. Patients were categorized as mSHOX2 positive or negative by cut-off. Metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using Cox regression and Log-rank analyses (median follow-up time: 60 months).
17 patients were mSHOX2 positive, showing unfavorable OS/CSS (Log-rank P = 0.004 and 0.02) and nearly 6-fold higher recurrence risk (hazard ratio 5.89, 95% CI 1.46-23.8). Multivariable Cox analysis confirmed mSHOX2 as an independent recurrence risk factor, disregarding TNM-based stratification.
mSHOX2 effectively identifies high-risk RCC patients post-surgery, indicating minimal residual disease. This easy to implement biomarker has potential for guiding of adjuvant therapy decisions.
American journal of translational research. 2024 Jan 15*** epublish ***
Thomas Büttner, Romina Zarbl, Philipp Krausewitz, Sebastian Strieth, Glen Kristiansen, Markus Eckstein, Damian J Ralser, Michael Hölzel, Manuel Ritter, Jörg Ellinger, Dimo Dietrich, Niklas Klümper
Department of Urology and Pediatric Urology, University Hospital Bonn Bonn, Germany., Department of Otorhinolaryngology, University Hospital Bonn Bonn, Germany., Institute of Pathology, University Hospital Bonn Bonn, Germany., Comprehensive Cancer Center EMN, University Hospital Erlangen Erlangen, Germany., Department of Gynaecology and Gynaecological Oncology, University Hospital Bonn Bonn, Germany., Institute of Experimental Oncology, University Hospital Bonn Bonn, Germany.