Significance of EpCAM and TROP2 expression in non-small cell lung cancer

Pak, Min Gyoung; Shin, Dong Hoon; Lee, Chang-Hun; Lee, Min Ki

doi:10.1186/1477-7819-10-53

Cited by 79 publications

(71 citation statements)

References 16 publications

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“…Consistently, these mRNA levels were increased more than 500-fold in biopsy tissue samples (Table 3). In contrast, several markers that have been reported to be expressed by CTCs in NSCLC (Hayes et al 2006;Pak et al 2012) showed no significant difference, e.g., cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM) ( Table 4).…”

Section: Identification Of Lung Adenocarcinoma-associated Genes In Pbmentioning

confidence: 47%

“…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).…”

Section: Selection Of Tumor Marker Genesmentioning

confidence: 99%

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Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

Man

Cao

Shi

et al. 2014

Tohoku J. Exp. Med.

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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), Ca 2+ -activated chloride channel-2 (CLCA2), hyaluronanmediated 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.

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Section: Identification Of Lung Adenocarcinoma-associated Genes In Pbmentioning

confidence: 47%

Section: Selection Of Tumor Marker Genesmentioning

confidence: 99%

Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

Man

Cao

Shi

et al. 2014

Tohoku J. Exp. Med.

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“…Tumor-associated calcium signal transducer protein (TROP)-2 is a transmembrane glycoprotein expressed at high levels in a variety of human epithelial tumors, including oral (6), pancreatic (7), gastric (8), ovarian (9), lung (10), and prostate cancer (11). By contrast, TROP-2 is barely detectable in non-cancerous tissues.…”

Section: Introductionmentioning

confidence: 99%

TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2

Zhao

Zhang

2018

Oncol Lett

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Abstract. High levels of tumor-associated calcium signal transduction protein (TROP)-2 have been demonstrated to be strongly associated with tumor necrosis factor (TNF)-α levels in colon cancer. In the present study, the effect of TNF-α on the regulation of TROP-2 expression and its effect in colon cancer cell migration and invasion were investigated in vitro. TROP-2 protein levels were evaluated in HCT-116 human colon cancer cells cultured with various concentrations of TNF-α using western blot analysis. Changes in the migratory and invasive potential of the cells were evaluated using a wound healing and transwell assay, respectively. Then, TROP-2 expression was downregulated in cells by use of siRNA, and TROP-2 knockdown was confirmed at the mRNA and protein level by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The migration and invasion potential of cells transfected with TROP-2 siRNA was also evaluated. Levels of several mitogen-activated protein kinase proteins, namely p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), were detected in cells treated with TNF-α using western blot analysis. The results demonstrated that TROP-2 protein levels increased in cells treated with lower concentrations of TNF-α, but decreased in cells treated with higher concentrations of TNF-α, compared with untreated control. Maximum TROP-2 levels were observed in cells treated with 20 µg/l TNF-α. Migration and invasion were enhanced in cells treated with 20 µg/l TNF-α. When TROP-2 was silenced in colon cancer cells by siRNA, migration and invasion were significantly decreased compared with control cells. TNF-α stimulation activated the ERK1/2 pathway, but did not significantly affect p38 and JNK phosphorylation levels. Treatment with a specific ERK1/2 inhibitor suppressed the TNF-α-induced upregulation of TROP-2 and the TNF-α-induced colon cancer cell migration and invasion. In conclusion, the present results demonstrated that low concentrations of TNF-α significantly enhanced colon cancer cell migration and invasion by upregulating TROP-2 via the ERK1/2 signaling pathway. IntroductionColon cancer is a common malignant tumor of the digestive tract, from which morbidity and mortality have been increasing in recent years. Tumor invasion and metastasis are the main causes of colon cancer-associated death, but the precise mechanism mediating these processes remains unclear. Previous studies have primarily focused on the characteristics of cancer cells; however, the effects of the tumor microenvironment on invasion and metastasis have increasingly been gaining attention in recent years (1).The tumor microenvironment has an important role in tumorigenesis and disease progression. Tumor necrosis factor (TNF)-α is an inflammatory cytokine frequently present in the tumor microenvironment. TNF-α is primarily secreted by tumor-associated macrophages and it initiates chronic inflammation (2). TNF-α has biphasic effects, by which it induces tumor cell apoptosis...

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“…Although the standard approach for capturing epithelial cells is to target EpCAM, it can be expressed moderately in normal lung epithelia and variably in different types of lung cancer. 20,21 Thus, not all target cells are expected to express EpCAM. A potential alternative capture antigen for lung epithelia is Trop2.…”

Section: Discussionmentioning

confidence: 99%

Interrogating Bronchoalveolar Lavage Samples via Exclusion-Based Analyte Extraction

et al. 2017

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Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.

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Significance of EpCAM and TROP2 expression in non-small cell lung cancer

Cited by 79 publications

References 16 publications

Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

Newly Identified Biomarkers for Detecting Circulating Tumor Cells in Lung Adenocarcinoma

TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2

Interrogating Bronchoalveolar Lavage Samples via Exclusion-Based Analyte Extraction

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