Detection of CTC Clusters and a Dedifferentiated RNA‐Expression Survival Signature in Prostate Cancer

Kozminsky, Molly; Fouladdel, Shamileh; Chung, Jin Hoon; Wang, Yugang; Smith, David C.; Alva, Ajjai; Azizi, Ebrahim; Morgan, Todd M.; Nagrath, Sunitha

doi:10.1002/advs.201801254

Cited by 38 publications

(48 citation statements)

References 35 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Circulating tumour cells (CTCs) analysis has recently emerged as a liquid biopsy approach for the early diagnosis [1,2], biomarker [3], evaluation of curative efficacy [4], evaluation of relapse [5] and prognostic prediction [6,7] in several solid tumours, including breast cancer [8,9],gastric cancer [10], prostate cancer [11], head and neck cancer [12], bladder cancer [13], and lung cancer [14][15][16]. CTCs also showed the potential efficacy in metastasis cancer, such as metastatic breast cancer [17,18] and colorectal cancer [19].…”

Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

View full text Add to dashboard Cite

Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. Conclusions: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

show abstract

Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Circulating tumour cells (CTCs) analysis has recently emerged as a liquid biopsy approach for the early diagnosis [1,2] , biomarker [3] , evaluation of curative efficacy [4] , evaluation of relapse [5] and prognostic prediction [6,7] in several solid tumours, including breast cancer [8,9] ,gastric cancer [10] , prostate cancer [11] , head and neck cancer [12] , bladder cancer [13] , and lung cancer [14][15][16] . CTCs also showed the potential efficacy in metastasis cancer, such as metastatic breast cancer [17,18] and colorectal cancer [19] .…”

Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

Zheng

Zhao

et al. 2019

Preprint

View full text Add to dashboard Cite

Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer.Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18.Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, sub solid nodules and nodules ≥8 mm.Conclusion: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, sub solid nodules and nodules ≥8 mm.

show abstract

“…We further investigate how the transition from individual migration to cluster-based migration is reflected in an increased probability to observe larger clusters by calculating the escape probability of clusters with different sizes (Supplementary Information -C). Similarly, a cluster size distribution from prostate cancer (14) shares similar traits but slightly larger tail, and maps well on to a larger cooperativity index (c=4) ( Fig. 3B).…”

Section: The Single Cell-cluster Migration Transition Recapitulates Cmentioning

confidence: 64%

“…second, a high migration cooperativity (c) that promotes collective, rather than solitary, cell migration ( This variability in the frequency of CTC clusters is well-supported by multiple independent experiments that reported variable fractions of CTC clusters in circulation (3,(14)(15)(16)(17)(18). These CTC cluster fractions indicate that different cancer types are characterized by different migratory regimes, that in turn correspond to different combinations of EMT rate and cooperativity (k, c) in the model (supplementary figure 3).…”

Section: The Rate Of Emt and Cell Cooperativity During Migration Givementioning

confidence: 82%

“…This simple physical model can quantitatively reproduce different cluster size distributions observed in the bloodstream of patients and/or in experimental mouse models. These experimental datasets exhibit a tremendous variability, ranging from cases where large clusters are highly improbable to cases of collective migration(4,14,(19)(20)(21)24), all of which can be captured by the model for varying parameter combinations.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A biophysical model of Epithelial-Mesenchymal Transition uncovers the frequency and size distribution of Circulating Tumor Cell clusters across cancer types

Bocci

2019

Preprint

View full text Add to dashboard Cite

The gain of cellular motility via the epithelial-mesenchymal transition (EMT) is considered crucial in the metastatic cascade. Cells undergoing EMT to varying extents are launched into the bloodstream as single circulating tumor cells (CTCs) or multi-cellular clusters. The frequency and size distributions of these multicellular clusters has been recently measured, but the underlying mechanisms enabling these different modes of migration remain poorly understood. We present a biophysical model that couples the epithelialmesenchymal phenotypic transition and cell migration to explain these different modes of cancer cell migration. With this reduced physical model, we identify a transition from individual migration to clustered cell migration that is regulated by the rate of EMT and the degree of cooperativity between cells during migration. This single cell to clustered migration transition can robustly recapitulate cluster size distributions observed experimentally across several cancer types, thus suggesting the existence of common features in the mechanisms of cell migration during metastasis. Furthermore, we identify three main mechanisms that can facilitate the formation and dissemination of large clusters: first, mechanisms that prevent a complete EMT and instead increase the population of hybrid Epithelial/Mesenchymal (E/M) cells; second, multiple intermediate E/M states that give rise to heterogeneous clusters formed by cells with different epithelial-mesenchymal traits; and third, non-cell-autonomous induction of EMT via cell-tocell signaling that gives rise to spatial correlations among cells in a tissue. Overall, this biophysical model represents a first step toward bridging the gap between the molecular and biophysical understanding of EMT and various modes of cancer cell migration, and highlights that a complete EMT might not be required for metastasis. Statement of significanceThe Epithelial-Mesenchymal Transition (EMT) confers motility and invasive traits to cancer cells. These cells can then enter the circulatory system both as single cells or as multi-cellular clusters to initiate metastases.We develop a biophysical model to investigate how EMT at the single cell level can give rise to a solitary or clustered cell migration. This model quantitatively reproduces cluster size distributions reported in human circulation and mouse models, therefore suggesting similar mechanisms in cancer cell migration across different cancer types. Moreover, we show that a partial EMT to a hybrid epithelial/mesenchymal cell state is sufficient to explain both single cell and clustered migration, therefore questioning the necessity of a complete EMT for cancer metastasis.

show abstract

Detection of CTC Clusters and a Dedifferentiated RNA‐Expression Survival Signature in Prostate Cancer

Cited by 38 publications

References 35 publications

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

A biophysical model of Epithelial-Mesenchymal Transition uncovers the frequency and size distribution of Circulating Tumor Cell clusters across cancer types

Contact Info

Product

Resources

About