Vimentin expression in circulating tumor cells (CTCs) associated with liver metastases predicts poor progression-free survival in patients with advanced lung cancer.
OBJECTIVE
To investigate the presence of vimentin expression in CTCs and its clinical relevance in patients with advanced lung cancer.


METHODS
Peripheral blood was obtained from 61 treatment-naive patients with advanced lung cancer. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was applied to identify, enumerate and characterize CTCs based on cell size, aneuploidy of chromosome 8 (Chr8) and vimentin expression. Quantification and analysis of CTCs were performed on patients before chemotherapy administration and after two cycles of therapy.


RESULTS
Before treatment, CTCs were detected in 60 (98.4%) patients, small cell CTCs (≤ 5 µm of WBCs) accounted for 52.8% of the absolute CTCs number, while 12 (19.7%) of the included patients had detectable vimentin-positive CTCs (vim+ CTCs). Liver metastases were reported in 7 (11.5%) patients and were significantly correlated to the presence of Vim+ CTCs (p = 0.002), with a high positivity rate of 71.4% (5/7). Vim+ CTCs were mostly in small cell size and Chr8 aneuploidy (77.0% and 82.05%, respectively). Baseline small cell CTCs ≥ 2/6 ml, triploid CTCs ≥ 2/6 ml, Vim+ CTCs ≥ 1/6 ml were found to significantly correlate with poor progression-free survival (PFS) (p = 0.017, p = 0.009 and p = 0.001, respectively). After adjusting for clinically significant factors, baseline Vim+ CTCs ≥ 1/6 ml was the only independent predictor of poor PFS [hazard ratio (HR):2.756, 95% confidence interval (CI): 1.239-6.131; p = 0.013].


CONCLUSIONS
This study demonstrates an important morphologic, karyotypic and phenotypic CTCs heterogeneity in advanced lung cancer patients. The majority of Vim+ CTCs are in small size and Chr8 aneuploidy. Baseline presence of Vim+ CTCs is correlated with liver metastases and may help predict poor PFS.
['Wang|Ying|Y|', 'Liu|Yanxia|Y|', 'Zhang|Lina|L|', 'Tong|Li|L|', 'Gao|Yuan|Y|', 'Hu|Fanbin|F|', 'Lin|Peter Ping|PP|', 'Li|Baolan|B|', 'Zhang|Tongmei|T|http://orcid.org/0000-0003-4271-3773']
D002898:Chromosomes, Human, Pair 8 D005260:Female D005500:Follow-Up Studies D006801:Humans D008113:Liver Neoplasms D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009360:Neoplastic Cells, Circulating D000077982:Progression-Free Survival D011446:Prospective Studies D014746:Vimentin
Vimentin Circulating tumor cells Progression-free survival Advanced lung cancer Cell size Aneuploidy of Chr8