Objectives: Biomarker measurements of minimal systemic disease have the potential to monitor the molecular status of lung carcinomas without invasive tumor biopsy at the time of treatment selection. The real-time reverse transcription polymerase chain reaction (qRT-PCR) is a valuable analytical tool for the detection of circulating tumor cells (CTCs) in the peripheral blood. The aim of this study was to investigate whether the detection of mRNA-positive CTCs could be useful for predicting disease recurrence, disease-free survival (DFS), and cancer specific survival (CSS) in NSCLC patients undergoing surgery.
Methods: We used real-time RT-PCR for absolute gene expression quantification of carcinoembryonic antigen (CEA, CEACAM5, NM004363), epidermal growth factor receptor 1 (EGFR1, NM 005228), lung specific X-protein (LUNX, PLUNC, NM016583) and hepatocyte growth factor receptor (c-met, MET, NM 000245) in the peripheral blood in a group of 129 patients with surgically treated non-small cell lung cancer.
Results: The detection of CEA mRNA-positive CTCs in peripheral blood was associated with shorter DFS (P<0.009; HR=2.64, 95% CI: 1.24-5.62), and CSS (P<0.007; HR=2.73, 95% CI: 1.28-5.81). CTCs status measured using EGFR, LUNX and c-met mRNA individually did not show any significant clinical relevance.
Conclusions: The role of CTCs in prognostication in non-small cell lung carcinoma (NSCLC) patients is controversial, but may be better defined with advancing technologies of detection of such cells with higher precision, and improved clinical-pathological correlations. Detection of CEA mRNA-positive CTCs in the peripheral blood after surgery in patients with stage I-IIIA NSCLC is highly predictive for DFS and CSS. This technique may be useful for identifying high-risk patients among surgically treated NSCLC cases.