Circulating tumor cells (CTC) and KRAS mutant circulating free DNA (cfDNA) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

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KRAS mutant circulating free DNA (cfDNA) and circulating tumor cell (CTC) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e15252 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e15252-e15252

Author(s):

Carmen Guillén Ponce ◽

Julie Earl ◽

Sandra Garcia Nieto ◽

Jose Carlos Martinez-Avila ◽

Jose Montans ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Cell ◽

Peripheral Blood ◽

Circulating Tumor Cell ◽

Circulating Free Dna ◽

Free Dna ◽

Exocrine Pancreatic Cancer

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428 KRAS mutant circulating free DNA (cfDNA) and circulating tumor cell (CTC) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer

European Journal of Cancer ◽

10.1016/s0959-8049(16)30262-3 ◽

2015 ◽

Vol 51 ◽

pp. S87

Author(s):

J. Earl ◽

S. Garcia-Nieto ◽

J.C. Martinez-Avila ◽

J. Montans ◽

A. Sanjuanbenito ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Cell ◽

Peripheral Blood ◽

Circulating Tumor Cell ◽

Circulating Free Dna ◽

Free Dna ◽

Exocrine Pancreatic Cancer

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EVALUATING MMP-2 AND TGFß-RI EXPRESSION IN CIRCULATING TUMOR CELLS OF PANCREATIC CANCER PATIENTS AND THEIR CORRELATION WITH CLINICAL EVOLUTION

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020190001e1433 ◽

2019 ◽

Vol 32 (2) ◽

Cited By ~ 3

Author(s):

José Luiz GASPARINI-JUNIOR ◽

Marcello Ferretti FANELLI ◽

Emne Ali ABDALLAH ◽

Ludmilla Thomé Domingos CHINEN

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Clinical Characteristics ◽

Epithelial Mesenchymal Transition ◽

Locally Advanced ◽

Progression Free Survival ◽

Clinical Findings ◽

Mesenchymal Transition

ABSTRACT Background: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. Aim: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). Method: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. Results: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. Conclusion: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.

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Circulating Tumor Cells Expressing Krüppel-Like Factor 8 and Vimentin as Predictors of Poor Prognosis in Pancreatic Cancer Patients

Cancer Control ◽

10.1177/10732748211027163 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110271

Author(s):

Peng Zhu ◽

Hui-Ying Liu ◽

Fu-Chen Liu ◽

Fang-Ming Gu ◽

Sheng-Xian Yuan ◽

...

Keyword(s):

Risk Factors ◽

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Prognostic Significance ◽

Immunomagnetic Separation ◽

Mesenchymal Transition

Background: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). Methods: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8+ and vimentin+ CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. Results: Patients with CTCs ( n = 30) had a higher relapse rate compared to those without ( n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8+/vimentin+ CTCs to total CTCs was inversely related to TTR ( r = −0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8+/vimentin+ ( P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8+/vimentin+ CTCs (both P < 0.05). Conclusion: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

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Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients

Cells ◽

10.3390/cells9020522 ◽

2020 ◽

Vol 9 (2) ◽

pp. 522 ◽

Cited By ~ 4

Author(s):

Patricia Mondelo-Macía ◽

Carmela Rodríguez-López ◽

Laura Valiña ◽

Santiago Aguín ◽

Luis León-Mateos ◽

...

Keyword(s):

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Copy Number ◽

Patients With Cancer ◽

Circulating Free Dna ◽

Free Dna ◽

Met Amplification ◽

Potential Biomarker

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10−10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch® and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.

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Characterization and prognostic significance of circulating tumor cells in the peripheral blood of patients with metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.4127 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 4127-4127 ◽

Cited By ~ 3

Author(s):

B. P. Negin ◽

N. J. Meropol ◽

R. K. Alpaugh ◽

K. Ruth ◽

C. McAleer ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Prognostic Significance ◽

Metastatic Pancreatic Cancer

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Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

Cellular Physiology and Biochemistry ◽

10.1159/000458736 ◽

2017 ◽

Vol 41 (2) ◽

pp. 755-768 ◽

Cited By ~ 93

Author(s):

Wei Zhang ◽

Wenjie Xia ◽

Zhengye Lv ◽

Chao Ni ◽

Yin Xin ◽

...

Keyword(s):

Personalized Medicine ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Liquid Biopsy ◽

Tumor Development ◽

Prognostic Information ◽

Source Characteristics ◽

Circulating Free Dna ◽

Free Dna ◽

And Personalized Medicine

Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional ‘solid biopsy’, which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning.

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Circulating tumor cells in peripheral blood of pancreatic cancer patients and their prognostic role: a systematic review and meta-analysis

HPB ◽

10.1016/j.hpb.2019.11.003 ◽

2020 ◽

Vol 22 (5) ◽

pp. 660-669 ◽

Cited By ~ 1

Author(s):

Yang Wang ◽

Xiaojin Yu ◽

Daniel Hartmann ◽

Jiahua Zhou

Keyword(s):

Systematic Review ◽

Pancreatic Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Meta Analysis ◽

Prognostic Role

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Low cytokeratin- and low EpCAM-expressing circulating tumor cells in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11046 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11046-11046 ◽

Cited By ~ 1

Author(s):

Daniel Adams ◽

Susan Tsai ◽

Olga V. Makarova ◽

Peixuan Zhu ◽

Shuhong Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Nuclear Structure ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Epithelial Mesenchymal Transition ◽

Size Exclusion ◽

Mesenchymal Transition ◽

Cytokeratin Expression ◽

Capture Techniques

11046 Background: To date, detecting circulating tumor cells (CTCs) in the peripheral blood of pancreatic patients using standard immuno-capture techniques has met with limited success. As pancreatic cancer is prone to metastasize at distant sites, and therefore should have high numbers of CTCs, it is possible that immuno-capture methods are not suitable for this disease. Using a microfiltration approach, we show that CTCs are present in the peripheral blood in over 75% of pancreatic cancer patients, and that two distinct subtypes can be identified. Methods: Pancreatic patient samples were provided by Medical College of Wisconsin, Milwaukee, WI. CellSieve microfilters, with precision 7 micron diameter pores distributed in uniform arrays were employed. 7.5 mL of whole blood was diluted in pre-fixation solution and filtered through CellSieve microfilters. CTCs collected by this size exclusion technique were fixed, permeabilized, and stained with DAPI, an antibody cocktail against cytokeratin 8, 18 and 19 (FITC), EpCAM (PE), and CD45 (Cy5). CTCs, defined as cytokeratin positive and CD45 negative, were found in two distinct subtypes. One subtype had the “classic” characteristics of a CTC, with high EpCAM and cytokeratin expression, identifiable cytokeratin filamentation, and a cancer-like nuclear structure. The second subtype is indicative of a CTC undergoing epithelial-mesenchymal transition (EMT), with low or no EpCAM, weak cytokeratin expression, and a smooth oval nuclear structure. Results: The “classic” CTCs were found in ~20% (n=40) of patient samples. The EMT-like CTCs were found in ~75% of the same patient cohort. Neither cell was present in any healthy subjects (n=30). EMT-like CTCs consistently lacked EpCAM expression and commonly presented as multi-cell clusters, or microemboli, in ~40% of the cases. Conclusions: We show that two distinct CTC subtypes circulate in the blood of most pancreatic patients. The low expression of cytokeratin and EpCAM of the EMT-like subtype implies that immuno-capture based CTC isolation methods have limited utility for pancreatic cancer. Further, this subtype provides a useful strategy for tracking pancreatic CTCs over the course of treatment.

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