eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood

Abstract Background Melanoma-associated antigen C2 (MAGEC2) is an oncogene associated with various cancer types. However, the biological function of MAGEC2 in circulating tumor cells is unclear. In this study, we investigated the role of MAGEC2 using adapted suspension cells (ASCs), which were previously developed to study circulating tumor cells (CTCs).Methods Differential gene expression between adherent cells (ADs) and ASCs was examined using RNA-seq analysis. MAGEC2 expression was assessed using RT-qPCR, immunoblotting, and ChIP-seq analysis. Depletion of MAGEC2 expression was carried out using siRNA. MAGEC2-depleted ADs and ASCs were used to investigate the change in proliferation rate and cell cycle. Then, the protein levels of STAT3, phosphorylated STAT3, and downstream of STAT3 were measured using control and MAGEC2-depleted ADs and ASCs. The direct effect of active STAT3 inhibition with Stattic in ASCs was also assessed in terms of proliferation and apoptosis. Finally, an Annexin V/7-AAD assay was performed to determine the percentage of apoptotic cells in Stattic-treated cells. Results MAGEC2 was highly expressed in ASCs compared to ADs. Depletion of MAGEC2 reduced the proliferation rate and viability of ASCs. To elucidate the underlying mechanism, the level of STAT3 was examined because of its oncogenic properties. Tyrosine-phosphorylated active STAT3 was highly expressed in ASCs and decreased in MAGEC2-depleted ASCs. In addition, when ASCs were treated with Stattic, an active STAT3 inhibitor, they were more sensitive to intrinsic pathway-mediated apoptosis.Conclusions High expression of MAGEC2 may play an important role in the survival of ASCs by maintaining the expression of activated STAT3 to prevent apoptotic cell death.

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Evaluating the Potential for Circulating Tumor Cells as a Diagnostic and Prognostic Biomarker in Various Cancer Types

10.31487/j.cocb.2020.01.05 ◽

2020 ◽

pp. 1-9

Author(s):

Crista E. Horton ◽

Humza Razaq

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Prognostic Biomarker ◽

Cost Effective ◽

Predictive Biomarker ◽

Standards Of Care ◽

The Past ◽

Clinical Literature ◽

Cancer Types ◽

Prognostic Implications

Circulating tumor cells (CTCs) are cells that can be found circulating in the peripheral blood of cancer patients. They originate from primary solid tumors and are thought to contribute to metastases and poor prognosis. Since cancer treatment is shifting toward greater personalization, a major goal in the field is the development of less invasive and more cost-effective measures in diagnosis, staging, treatment, prognostic implications, and surveillance of cancer. Utilizing CTCs as a biomarker from a “liquid biopsy” or sample of patients’ blood would be transformative in accomplishing this goal. In this review, we aim to critically assess current pre-clinical and clinical literature over the past two decades implicating CTCs’ potential for use as a predictive biomarker in various cancer types either in addition to or instead of current standards of care. We also are interested in understanding several aspects of CTCs including the role CTCs play in resistance to treatment, the immune system evasion properties of CTCs, the feasibility of using CTCs in clinical practice, and the utility of CTCs for predicting outcomes including patient survival. Furthermore, here we discuss gaps in the literature, limitations of CTCs, potential for their other uses, as well as the significance of CTC detection in patients following surgery.

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PP 69 Antibody-independent enrichment of live circulating tumor cells (CTCs) from a variety of cancer types

European Journal of Cancer ◽

10.1016/s0959-8049(11)72647-8 ◽

2011 ◽

Vol 47 ◽

pp. S16

Author(s):

C. Sachsenmaier ◽

V. Gupta ◽

M. Garza ◽

B. Redden ◽

G. Copper ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Types

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Capture of Viable Circulating Tumor Cells in the Liver of Colorectal Cancer Patients

Clinical Chemistry ◽

10.1373/clinchem.2013.202846 ◽

2013 ◽

Vol 59 (9) ◽

pp. 1384-1392 ◽

Cited By ~ 120

Author(s):

Eric Denève ◽

Sabine Riethdorf ◽

Jeanne Ramos ◽

David Nocca ◽

Amandine Coffy ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Tumor Resection ◽

Reference Method ◽

Biological Properties ◽

Cancer Types ◽

Colorectal Cancer Patients

BACKGROUND The incidence and number of circulating tumor cells (CTCs) in the peripheral blood of colorectal cancer patients are lower than in other cancer types, which may point to a particular biology of colorectal cancer affecting CTC detection. METHODS We detected CTCs in the peripheral and mesenteric blood of colorectal cancer patients by use of 2 independent technologies on the basis of different biological properties of colon cancer cells. Seventy-five patients diagnosed with localized (M0, n = 60) and metastatic (M1, n = 15) colorectal cancer were included. Peripheral and mesenteric blood samples were collected before tumor resection. We performed CTC enumeration with an EpCAM-independent enrichment method followed by the Epispot assay that detected only viable CK19-releasing CTCs. In parallel, we used the FDA-cleared EpCAM-dependent CellSearch® as the reference method. RESULTS The enumeration of CK19-releasing cells by the CK19-Epispot assay revealed viable CTCs in 27 of 41 (65.9%) and 41 of 74 (55.4%) (P = 0.04) patients in mesenteric and peripheral blood, respectively, whereas CellSearch detected CTCs in 19 of 34 (55.9%) and 20 of 69 (29.0%) (P = 0.0046) patients. In mesenteric blood, medians of 4 (range 0–247) and 2.7 CTCs (range 0–286) were found with Epispot and CellSearch (P = 0.2), respectively, whereas in peripheral blood, Epispot and CellSearch detected a median of 1.2 (range 0–92) and 0 CTCs (range 0–147) (P = 0.002). CONCLUSIONS A considerable portion of viable CTCs detectable by the Epispot assay are trapped in the liver as the first filter organ in CRC patients.

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