Circulating Tumor Cells in Lung Cancer

Abstract

Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a ‘liquid biopsy’ is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment.

Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis

“…However, profilin-1 knockdown did not affect the distant metastasis of lung cancer cell. Because only a rare portion of invaded cells could survive in the peripheral blood and surviving CTC successfully form distant metastasis are even rarer 41,42 , the invasion of cancer cells does not necessarily ensure their distal metastatic growth. Unlike profilin-1, the increased CTC concentration caused by profilin-2 overexpression was accompanied by a significantly increased tumour size.…”

Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

“…Gene markers were compiled from recent literature with reference to CTC detection in lung cancer (Sher et al 2005;Hayes et al 2006;Jacob et al 2007;Xi et al 2007;Okumura et al 2009;Mavroudis 2010;Sanchez-Palencia et al 2011;Pak et al 2012;Young et al 2012). Accordingly, the following 48 genes were selected: genes upregulated in lung cancer, including carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), collagen type XI alpha 1 (COL11A1), ceruloplasmin (CP), chemokine (C-X-C motif) ligand 13 (CXCL13), gremlin 1 (GREM1), marker of proliferation Ki-67 (MKI67), matrix metallopeptidase 1(MMP1), matrix metallopeptidase 12 (MMP12), serine peptidase inhibitor, Kazal type 1 (SPINK1), secreted phosphoprotein 1 (SPP1), topoisomerase (DNA) II alpha 170kDa (TOP2A), TOX high mobility group box family member 3 (TOX3); tumor metastasis genes, including annexin A5 (ANXA5), dual specificity phosphatase 6 (DUSP6), v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 (ERBB3), hepatocyte growth factor (HGF), hyaluronan-mediated motility receptor (HMMR), interferon regulatory factor 4 (IRF4), lymphocyte-specific protein tyrosine kinase (LCK), met proto-oncogene (MET), monocyte to macrophage differentiation-associated protein (MMD), neurofibromin 1 (NF1), signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2); genes differentially expressed in adenocarcinoma vs. squamous cell carcinoma, including Ca 2+ -activated chloride channel-2 (CLCA2), desmoglein 3 (DSG3), keratin 5 (KRT5), keratin 14 (KRT14), small proline-rich protein 1A (SPRR1A), anterior gradient 2 (AGR2), lens protein with glutamine synthetase domain (LGSN), NK2 homeobox 1 (NKX2-1), surfactant associated 3 (SFTA3), serine peptidase inhibitor Kazal type 1 (SPINK1); other genes relating to CTCs in lung cancer, including cytokeratin 7 (CK7), thyroid Transcription Factor-1 (TTF-1), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTERT), baculoviral IAP repeat containing 5 (BIRC5 or Survivin), surfactant protein B (SFTPB), cytokeratin 20 (CK20), BMI1 polycomb ring finger oncogene (BMI-1), mucin 16, cell surface associated carbohydrate antigen (CA125), fibronectin 1 (FN1), epithelial cell adhesion molecule (EpCAM), snail zinc finger protein (SNAIL), cytokeratin 19 (CK19), and basic helix-loop-helix transcription factor twist (TWIST).…”

Predictive and prognostic value of circulating tumor cell detection in lung cancer: A clinician's perspective

“…Circulating tumor cells (CTCs) are cells shed from either primary or secondary tumors that migrate into the circulatory system, and are thought to be responsible for the development of distant metastases [4][5][6]. CTCs are extremely rare, occurring at a frequency as low as 1 CTC per 10 6 -10 7 leukocytes, with even lower numbers in early stage disease [4].…”

“…CTCs are extremely rare, occurring at a frequency as low as 1 CTC per 10 6 -10 7 leukocytes, with even lower numbers in early stage disease [4]. To date, the phenotype of CTCs has not been fully defined.…”