Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer.
OBJECTIVE
Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC.


METHODS
DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed.


RESULTS
KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; kappa = 0.668; P < 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P < 0.001).


CONCLUSIONS
KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
Shuhang
S
Wang
Tongtong
T
An
Jie
J
Wang
Jun
J
Zhao
Zhijie
Z
Wang
Minglei
M
Zhuo
Hua
H
Bai
Lu
L
Yang
Yan
Y
Zhang
Xin
X
Wang
Jianchun
J
Duan
Yuyan
Y
Wang
Qingzhi
Q
Guo
Meina
M
Wu
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004247:DNA / Q000097:blood*; D004252:DNA Mutational Analysis / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010949:Plasma; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D004247:DNA; D066246:ErbB Receptors