Genetic analysis of circulating tumor cells in pancreatic cancer patients: A pilot study

Görner, Karin; Bachmann, Jeannine; Holzhauer, C.; Kirchner, Roland; Raba, Katharina; Fischer, Johannes C.; Martignoni, Marc E.; Schiemann, Matthias; Alunni-Fabbroni, Marianna

doi:10.1016/j.ygeno.2015.02.003

Cited by 16 publications

(5 citation statements)

References 34 publications

(36 reference statements)

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“…The presence of CTCs has been associated with poor prognosis and treatment responses in the clinical setting [ 50 ] and CTCs can also be used as predictive markers to increase treatment efficacy [ 51 ]. This could eventually reduce healthcare costs and be a valuable tool for personalized treatment [ 52 , 53 , 54 ].…”

Section: Circulating Tumor Cell Analysis Approachesmentioning

confidence: 99%

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

et al. 2018

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The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch® and Parsortix™ platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside.

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Section: Circulating Tumor Cell Analysis Approachesmentioning

confidence: 99%

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

et al. 2018

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“…Therefore, early detection and dynamic monitoring of disease progression are crucial for better clinical outcome of pancreatic cancers [ 6 ]. Conventional imaging examinations such as contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) often fails to detect small primary tumors and small metastasis, optimal treatment opportunities are usually missed [ 8 ]. Although carbohydrate antigen 19-9 (CA19-9) is widely used in clinical practice, it is insensitive for early invasive pancreatic cancer and hard to discriminate some pancreatic cancers from benign diseases [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of pancreatic circulating tumor cells using combined negative enrichment and immunostaining-fluorescence in situ hybridization

Gao

Zhu

Zhang³

et al. 2016

J Exp Clin Cancer Res

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BackgroundCirculating tumor cells (CTCs) hold great potential in both clinical application and basic research for the managements of cancer. However, it remains to be an enormous challenge to obtain efficient detection of pancreatic CTCs. New detection platforms for the detection of pancreatic CTCs are urgently required.MethodsIn the present study, we applied a newly-developed platform integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) to analyze clinical significance of pancreatic CTCs. Immunostaining of CK, CD45, DAPI and FISH with the centromere of chromosome 8 (CEP8) were utilized to identify CTCs. Cells with features of CK+/CD45-/DAPI+/CEP8 = 2, CK+/CD45-/DAPI+/CEP8 > 2, CK-/CD45-/DAPI+/CEP8 > 2 were defined as pancreatic CTCs. The Kaplan-Meier method and Cox proportional hazards model were used to analyze the relationship of CTC level and other clinicopathological factors with pancreatic cancer clinical outcomes.ResultsCTC count in pancreatic cancer was higher than healthy individuals (median, 3 vs 0 per 7.5 ml; P < 0.001). SE-iFISH platform yielded a sensitivity of 88 % and specificity of 90 % in pancreatic cancer at the cutoff value of 2 cells/7.5 ml. Pancreatic cancer patients with lower CTC count (<3/7.5 ml) had substantially better overall survival (OS) compared with these with higher CTC count (≥3/7.5 ml) (15.2 vs 10.2 months, P = 0.023). Multivariate analysis indicated that higher CTC count was a strong indicator for worse OS (HR = 4.547, P = 0.016).ConclusionOur current data showed that CTCs could be detected in pancreatic cancer patients in various stages, whether localized, locally advanced and metastatic. Besides, CTCs have shown the potential implication in predicting prognosis of pancreatic cancer.

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“…As the American Society of Clinical Oncology and the College of American Pathologists have highlighted in a recommendation paper, indeed, further studies with standardized technologies are needed to introduce LB in clinical practice [54]. Of note, the introduction of the analysis with LB of epigenetic markers [55,56], of exosome-derived DNA [22,36], and of gene expression profiling/circulating proteins [35,57,58] may represent important steps in improving this kind of non-invasive approach for the molecular characterization of PDAC. Particularly, about epigenetic alterations, DNA methylation may represent a very promising horizon in this changing scenario.…”

Section: Discussionmentioning

confidence: 99%

Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine

Luchini

Veronese

Nottegar

et al. 2019

Cancers

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Liquid biopsy (LB) is a non-invasive approach representing a promising tool for new precision medicine strategies for cancer treatment. However, a comprehensive analysis of its reliability for pancreatic cancer (PC) is lacking. To this aim, we performed the first meta-analysis on this topic. We calculated the pooled sensitivity, specificity, positive (LR+) and negative (LR−) likelihood ratio, and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall accuracy. We finally assessed the concordance rate of all mutations detected by multi-genes panels. Fourteen eligible studies involving 369 patients were included. The overall pooled sensitivity and specificity were 0.70 and 0.86, respectively. The LR+ was 3.85, the LR- was 0.34 and DOR was 15.84. The SROC curve with an AUC of 0.88 indicated a relatively high accuracy of LB for molecular characterization of PC. The concordance rate of all mutations detected by multi-genes panels was 31.9%. LB can serve as surrogate for tissue in the molecular profiling of PC, because of its relatively high sensitivity, specificity and accuracy. It represents a unique opportunity to be further explored towards its introduction in clinical practice and for developing new precision medicine approaches against PC.

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Genetic analysis of circulating tumor cells in pancreatic cancer patients: A pilot study

Cited by 16 publications

References 34 publications

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis

Clinical significance of pancreatic circulating tumor cells using combined negative enrichment and immunostaining-fluorescence in situ hybridization

Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine

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