Preliminary Investigation of the Clinical Significance of Detecting Circulating Tumor Cells Enriched from Lung Cancer Patients

Wu, Chi-Fang; Hao, Huaijie; Li, Longyun; Zhou, Xin; Guo, Zijian; Zhang, Li; Zhang, Xiaolin; Zhong, Wei; H, Guo; Bremner, Ross M.; Lin, Peter Ping

doi:10.1097/jto.0b013e3181914125

Cited by 92 publications

(75 citation statements)

References 25 publications

(30 reference statements)

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“…CTCs were detected in 47 cases (71.21%), and the detection rate was higher than in similar studies using other detection methods (Wu et al, 2009;Zhou et al, 2010). Furthermore, none of the 20 patients in the control group were found to be CTCpositive, indicating that the CTC detection system has high sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 69%

Detecting circulating tumor cells in patients with advanced non-small cell lung cancer

Xu¹,

Zhou²,

Pan³

2015

Genet. Mol. Res.

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ABSTRACT. We explored the expression and clinical significance of circulating tumor cells (CTCs) in patients with advanced non-small cell lung cancer (NSCLC). Sixty-six patients with advanced NSCLC at the Oncology Department of Jinzhou Hospital were selected as an observation group between February and December 2013. Healthy volunteers and 20 benign lung disease patients were taken as a control group. Peripheral blood CTCs in the observation and control groups were detected using the CellSearch ® . CTC detection and analysis system, and the relationship between the expression and clinical effect of CTCs and disease progression was analyzed. Peripheral blood CTCs were observed in 47 of the 66 observation group cases (71.21%), but none were found in the control group (P < 0.05). The CTC-positive rate was independent of NSCLC patients' age, gender, smoking habits, histological features, and degree of differentiation (P > 0.05). The CTCpositive rate correlated with pathological staging (P < 0.05). After two Tumor cell and non-small cell carcinoma courses of chemotherapy, the number of cases with CTCs ≥3 decreased significantly, compared with pre-chemotherapy cases (P < 0.05), and the disease did not progress in 37 cases (34 cases with <3 CTCs and three cases with ≥3 CTCs). Eight cases displayed disease progression, of which five cases had <3 CTCs and three cases had ≥3CTCs. There was a statistically significant correlation between CTC changes and disease progression (P < 0.05). The CTC-positive rate correlated with the pathological staging and changes in the number of CTCs were associated with chemotherapy efficacy and disease progression.

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Section: Discussionmentioning

confidence: 69%

Detecting circulating tumor cells in patients with advanced non-small cell lung cancer

Xu¹,

Zhou²,

Pan³

2015

Genet. Mol. Res.

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“…Although SCLC is often referred to as a neuroendocrine tumor, it is an epithelial tumor that co-expresses neural, endocrine, and epithelial markers 37 and so as we show, the latter can be exploited for detec- 38 A second preliminary study of lung cancer patients conducted using unvalidated manual technology and where just 13 patients had SCLC, found CTCs in a similar proportion of patients to that reported here but with smaller numbers than we observed. 39 To our knowledge this is the first report on CellSearch technology applied to patients with SCLC. We demonstrate detection of CTCs in the majority of patients, and in abundance compared with other types of cancer.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Hou

Greystoke

Lancashire

et al. 2009

The American Journal of Pathology

210

183

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Serological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30 , M65 , lactate dehydrogenase , and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis , both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy , whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22 , mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity , respectively. Our results provide a rationale to include the use of serological biomark- Small cell lung cancer (SCLC) is initially chemosensitive but invariably relapses with a chemoresistant phenotype.1 A number of molecularly targeted therapies have been evaluated attempting to improve outcome, but none have succeeded to date.2 Ideally, early clinical trials should incorporate validated pharmacodynamic biomarkers, conducted to good clinical laboratory practice, that demonstrate both proof of mechanism (drug hits target) and proof of concept (tumor responds to drug).3 Although possible, serial biopsies are rare in SCLC, and the tissue obtained often insufficient for extensive molecular profiling. Thus, there is a pressing need for blood-based biomarkers that report therapeutic response.Assays of drug-induced cell death are potential proof of concept biomarkers for multiple therapeutics. 4 The M30 Apoptosense and M65 assays (Peviva, Bromma, Sweden) detect cytokeratin (CK) 18, expressed in epithelial but not hematopoietic cells, and released into the blood following cytoskeletal disassembly and degradation during apoptotic and/or necrotic cell death. 5 The M30 antibody recognizes a caspase-cleaved neoepitope of CK18 that is only revealed during apoptosis, whereas the M65 assay detects full length and cleaved forms of CK18 reporting apoptosis and necrosis.6 Nucleosomal DNA (nDNA) results from cleavage of chromatin by apoptotic endonucleases into membrane bound DNA fragments that are phagocytosed by macrophages and sub-

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“…Thus, we only extracted the patients' clinical characteristics in this article. Finally, we enrolled 12 Yamashita et al, 2000;Sher et al, 2005;Chen et al, 2007;Liu et al, 2008;Hou et al, 2009;Yoon et al, 2011;Hou et al, 2012;Nieva et al, 2012) articles containing survival outcomes and patients' clinical characteristics and 15 articles (Castaldo et al, 1997;Peck et al, 1998;Li et al, 2005;Hayes et al, 2006;Sheu et al, 2006;Huang et al, 2007;Sawabata et al, 2007;Guo et al, 2009;Okumura et al, 2009;Tanaka et al, 2009;Wu et al, 2009;Farace et al, 2011;Devriese et al, 2012;Wendel et al, 2012) containing only patients' clinical characteristics in our analysis (Figure 1). These studies were published between the year of 1997 and 2012.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…We stratified the studies (Peck et al, 1998;Yamashita et al, 2000;Sher et al, 2005;Sheu et al, 2006;Chen et al, 2007;Liu et al, 2008;Okumura et al, 2009;Tanaka et al, 2009;Jemal et al, 2011;Yoon et al, 2011;Hou et al, 2012;Wendel et al, 2012), (Castaldo et al, 1997;Li et al, 2005;Hayes et al, 2006;Huang et al, 2007;Sawabata et al, 2007;Guo et al, 2009;Wu et al, 2009;Farace et al, 2011;Devriese et al, 2012; to observe the correlation between each clinical characteristic and CTCs appearance in peripheral blood in lung cancer patients. As shown in table 4, CTCs were more likely to show up in peripheral blood in III/IV lung cancer patients than I/II patients using samples collected from all their time points, especially using post-treatment samples (OR= 4.86 [2.29,10.29], p < 0.0001) ( Figure 3).…”

Section: Correlation Between Ctcs Appearance In Peripheral Blood and mentioning

confidence: 99%

Meta-analysis of Circulating Tumor Cells as a Prognostic Marker in Lung Cancer

Xiao²,

Liu³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Preliminary Investigation of the Clinical Significance of Detecting Circulating Tumor Cells Enriched from Lung Cancer Patients

Cited by 92 publications

References 25 publications

Detecting circulating tumor cells in patients with advanced non-small cell lung cancer

Detecting circulating tumor cells in patients with advanced non-small cell lung cancer

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Meta-analysis of Circulating Tumor Cells as a Prognostic Marker in Lung Cancer

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