Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

YINGCHUN MAN,^1,2 JINGYAN CAO,¹ SHI JIN,¹ GANG XU,¹ BO PAN,¹ LIHUA SHANG,¹ DEHAI CHE,¹ QIN YU³ and YAN YU¹

¹Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, P.R. China
²Department of Medical Oncology, General Hospital of Heilongjiang Province Land Reclamation Headquarter, The Second Hospital of Heilongjiang Province, Harbin, P.R. China
³Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, P.R. China

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.

keywords —— Ca²⁺-activated chloride channel-2; circulating tumor cells; cytokeratin 7; hyaluronan-mediated motility receptor; telomerase catalytic subunit

===============================

Tohoku J. Exp. Med., 2014, 234, 29-40

Correspondence: Yan Yu, Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Haping road 150, Nangang district, Harbin, Heilongjiang province 150010, P.R. China.

e-mail: manyingchun@126.com