TTF-1 mRNA-positive circulating tumor cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients

Abstract

Circulating tumor cells (CTCs) have been identified in peripheral blood of cancer patients, and reproducible detection of CTCs has demonstrated the potential as useful diagnostic and prognostic tools in several cancers. Present study aimed to determine the clinical relevance of CTCs in surgically resected non-small cell lung cancer (NSCLC) patients. CTC status in presurgery and postsurgery peripheral blood samples from 79 surgically resected NSCLC patients was investigated using thyroid transcription factor-1 (TTF-1) and cytokeratin19 (CK19) mRNA markers by nested real-time RT (reverse transcription)-PCR assay. Detection of TTF-1 (+)CTCs was found to be specific to NSCLC patients. TTF-1 (+)CTCs were detected in 36.1% (22/61) of patients before surgery and in 37.5% (18/48) after surgery. For CK19 mRNA-expressing CTCs (CK19 (+)CTCs), the detection rate was 42.6% (26/61) before surgery, and 25.0% (12/48) after surgery. Cases with postsurgery TTF-1 (+) and/or CK19 (+)TCs was more associated with disease progression ( P = 0.004) and shorter disease progression-free survival ( P = 0.006) as compared to those without postsurgery CTCs. As an individual marker, postsurgery TTF-1 (+)CTCs-positive status was more associated with disease progression ( P = 0.004) and shorter disease progression-free survival ( P = 0.004) as compared to postsurgery TTF-1 (+)CTCs-negative status. Particularly, patients with postsurgery TTF-1 (+)CTCs, but not presurgery (Pre (−)Post (+) cases) showed marked shorter disease progression-free survival than other patients ( P < 0.001). On the other hand, a CK19 (+)CTC status individually did not show significant clinical relevance, and presurgery CK19 (+)CTC status did not either. Present study suggests that TTF-1 mRNA-expressing CTCs might be a useful surrogate predictor of disease progression before clinical manifestations are apparent, and that monitoring of TTF-1 (+)CTCs status after surgery may be useful for identifying high-risk patients among surgically resected NSCLC cases.