Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

• Published in: The Tohoku Journal of Experimental Medicine Vol. 234; no. 1; pp. 29 - 40
• Main Authors: Man, Yingchun, Cao, Jingyan, Jin, Shi, Xu, Gang, Pan, Bo, Shang, Lihua, Che, Dehai, Yu, Qin, Yu, Yan
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01-09-2014
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma of Lung; Analysis of Variance; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Ca2+-activated chloride channel-2; Chloride Channels - genetics; Chloride Channels - metabolism; circulating tumor cells; cytokeratin 7; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Genetic Association Studies; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; hyaluronan-mediated motility receptor; Keratin-7 - genetics; Keratin-7 - metabolism; Lung Neoplasms - diagnosis; Neoplastic Cells, Circulating - chemistry; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sensitivity and Specificity; Statistics, Nonparametric; Telomerase - genetics; Telomerase - metabolism; telomerase catalytic subunit
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.234.29

Circulating tumor cells (CTCs) have been implicated in cancer prognosis and follow up. Detection of CTCs was considered significant in cancer evaluation. However, due to the heterogeneity and rareness of CTCs, detecting them with a single maker is usually challenged with low specificity and sensitivity. Previous studies concerning CTCs detection in lung cancer mainly focused on non-small cell lung carcinoma. Currently, there is no report yet describing the CTC detection with multiple markers in lung adenocarcinoma. In this study, by employing quantitative real-time PCR, we identified four candidate genes (mRNA) that were significantly elevated in peripheral blood mononuclear cells and biopsy tissue samples from patients with lung adenocarcinoma: cytokeratin 7 (CK7), Ca2+-activated chloride channel-2 (CLCA2), hyaluronan-mediated motility receptor (HMMR), and human telomerase catalytic subunit (hTERT). Then, the four markers were used for CTC detection; namely, positive detection was defined if at least one of the four markers was elevated. The positive CTC detection rate was 74.0% in patients with lung adenocarcinoma while 2.2% for healthy controls, 6.3% for benign lung disease, and 48.0% for non-adenocarcinoma non-small cell lung carcinoma. Furthermore, in a three-year follow-up study, patients with an increase in the detection markers of CTCs (CK7, CLCA2, HMMR or hTERT) on day 90 after first detection had shorter survival time compared to those with a decrease. These results demonstrate that the combination of the four markers with specificity and sensitivity is of great value in lung adenocarcinoma prognosis and follow up.