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Int. J. Mol. Sci. 2016, 17(11), 1845; doi:10.3390/ijms17111845

Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

1
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China
2
Department of Thoracic Tumor Chemotherapy, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China
3
Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou 310022, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 16 August 2016 / Revised: 25 October 2016 / Accepted: 27 October 2016 / Published: 5 November 2016
(This article belongs to the Special Issue Liquid Biopsy for Clinical Application)
View Full-Text   |   Download PDF [2115 KB, uploaded 5 November 2016]   |  

Abstract

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients. View Full-Text
Keywords: non-small-cell lung carcinoma (NSCLC); circulating tumor cells (CTCs); peripheral blood mononuclear cells (PBMCs); cell-free RNA content; prognosis non-small-cell lung carcinoma (NSCLC); circulating tumor cells (CTCs); peripheral blood mononuclear cells (PBMCs); cell-free RNA content; prognosis
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Yu, X.-M.; Wu, Y.-C.; Liu, X.; Huang, X.-C.; Hou, X.-X.; Wang, J.-L.; Cheng, X.-L.; Mao, W.-M.; Ling, Z.-Q. Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma. Int. J. Mol. Sci. 2016, 17, 1845.

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