Investigation of transrenal KRAS mutation in late stage NSCLC patients correlates to disease progression

Abstract

Purpose: Using transrenal DNA to detect KRAS mutations in non-small cell lung cancer (NSCLC), the study addressed the clinical impact for longitudinal monitoring and prognostic value for disease outcome.

Methods: Digital droplet PCR was used to detect the mutant DNA. A total of 200 NSCLC patients were recruited with varying molecular profiles. To ascertain the specificity of transrenal DNA to accurately profile the disease, primary tissues were compared. Subsequently, serial samplings were performed at different treatment cycles to gauge the predictive value.

Results: Transrenal DNA was successfully detected in all 200 patients. Overall concordance rate for mutant KRAS DNA within urine specimens and primary tissue biopsies was 95% (k = 0.87; 95% CI: 0.82–0.95). Patients with positive results at baseline had lower median overall survival (OS) than the wildtype group. More importantly, longitudinal monitoring of urine specimens showed an increase in the quantity of transrenal DNA, which were highly associated with disease progression and outcome.

Conclusions: Our study showed a highly associative link to the patient’s tumor KRAS profile. Monitoring its variations aided in stratifying patients with worse outcome. Urinary specimens that can be extracted non-invasively presents new opportunities to track patients with KRAS mutation undergoing therapy.

Keywords:

• NSCLC
• transrenal DNA
• cell free DNA
• KRAS mutation
• liquid biopsy
• circulating tumor DNA

Acknowledgements

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by a research grant provided by Wuhan No. 6 Hospital, Affiliated Hospital to Jianghan University, Wuhan [201310326].