Urinary cell-free DNA as a prognostic marker for KRAS-positive advanced-stage NSCLC

Abstract

Background: KRAS mutations are prevalent in non-small cell lung cancer (NSCLC) but its clinical implications remain to be determined. Continual profiling of KRAS mutations in patients is challenging, and the study aims to determine the potential use of urinary DNA in disease predictions.

Methods: A total of 150 patients were recruited. To ascertain the clinical relevance of urinary DNA, matched tumor profiles were analyzed. Serial measurements were taken to gauge the reliability of the assay. These results were correlated to overall survival using the Kaplan-Meier estimate.

Results: A good overall concordance of 93% (consolidated results from serial measurements) was achieved between tumor tissue and urinary DNA profiling. Of the discordant KRAS cases, we observed subsequent positive detection during monitoring and very low concentrations of mutant DNA. In addition, we noted that KRAS-positive patients detected using urinary DNA have good prognostic utility. Interestingly, we also observed that the trend is highly correlative of the rate of change in KRAS mutant DNA concentrations and the period of monitoring.

Conclusions: Urinary DNA offered a non-invasive approach to probe NSCLC dynamics, and in our study we showed that it had predictive capabilities for KRAS-positive patients. Serial monitoring of urinary samples showed that it had a predictive role in identifying patients with worse outcome.

Keywords: Disease prognosis; KRAS; Non-invasive liquid biopsy; Non-small cell lung cancer.