Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome

Ramcharan, K. S.; Lip, Gregory Y.H.; Stonelake, Paul S.; Blann, Andrew D.

doi:10.1007/s00384-014-2116-3

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…Studies from CEC counts prior to liver resections reported 5/mL (CellSearch, 140 patients) or 10 vs. 20/mL for patients with respectively good (n = 102) or poor (n = 52) outcome, (CD34 + CD45 − CD146 + measured by FACS). [20,21]. In this study, a significant higher CEC count after three cycles of chemotherapy (p = 0.00), with a nearly 2-fold increase (48 to 90/4 mL) was detected.…”

Section: Discussionsupporting

confidence: 50%

“…Malka et al [14] showed increase in PFS but not for OS (cut off 23 CEC/mL based on CD31 + CD146 + CD45neg7AADneg viable cells/mL by FACS analysis) in 97 patients from the randomized phase II FNCLCC ACCORD 13/0503 trial, receiving first line palliative systemic therapy with bevacizumab with either XELIRI or FOLFIRI. In patients undergoing resection for colorectal liver metastases CEC counts (CD34 + CD45negCD146 + ) before surgery did not have additional value in predicting 2 year outcome [21].…”

Section: Discussionmentioning

confidence: 80%

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CD276-Positive Circulating Endothelial Cells Do Not Predict Response to Systemic Therapy in Advanced Colorectal Cancer

Gootjes

Kraan

Buffart

et al. 2020

Cells

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CD276 can discriminate between tumor derived and normal CECs (circulating endothelial cells). We evaluated whether CD276+CEC is a clinically relevant biomarker to predict response to palliative systemic therapy in patients with metastatic colorectal cancer (mCRC). Samples were prospectively collected from patients with mCRC enrolled in the ORCHESTRA trial (NCT01792934). At baseline and after three cycles of 5-fluorouracil/leucovorin and oxaliplatin ± bevacizumab, CECs were measured by flowcytometry (CD34+CD45negCD146+DNA+; and CD276+). A clinically relevant cut-off value of (CD276+)CECs was determined as 100% sensitivity (and 80% specificity in 95% confidence interval) identifying patients with progressive disease within 6 months. There were 182 baseline samples and 133 follow up samples available for analysis. CEC and CD276+CEC counts significantly increased during treatment from 48 to 90 CEC/4 mL (p = 0.00) and from 14 to 33 CD276+CEC/4 mL (p = 0.00) at baseline and at first evaluation, respectively. CEC and CD276+CEC counts were not predictive for poor response (area under the curve (AUC) 0.53 for CEC and AUC 0.52 for CD276+CEC). Despite numerical changes during therapy, CEC and CD276+CEC counts do not adequately predict poor response to first line palliative systemic therapy in patients with mCRC.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 80%

CD276-Positive Circulating Endothelial Cells Do Not Predict Response to Systemic Therapy in Advanced Colorectal Cancer

Gootjes

Kraan

Buffart

et al. 2020

Cells

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“…Since CECs are rare events, their precise quantification in peripheral blood (PB) samples requires a technically rigorous analytical approach, which should take many factors into consideration (8). Several pre-analytical and analytical steps significantly affect not only the quantification of CECs, but can also result in a change in the definition of these cells, leading to problems in the interpretation of the results (Table I) and in their potential association with clinical endpoints (Table II) (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Flow Cytometric Analysis Of Circulating Endothelial Cells Inmentioning

confidence: 99%

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Danova

Comolli

Manzoni

et al. 2016

Molecular and Clinical Oncology

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Abstract. Malignant tumors are characterized by uncontrolled cell growth and metastatic spread, with a pivotal importance of the phenomenon of angiogenesis. For this reason, research has focused on the development of agents targeting the vascular component of the tumor microenvironment and regulating the angiogenic switch. As a result, the therapeutic inhibition of angiogenesis has become an important component of anticancer treatment, however, its utility is partly limited by the lack of an established methodology to assess its efficacy in vivo. Circulating endothelial cells (CECs), which are rare in healthy subjects and significantly increased in different tumor types, represent a promising tool for monitoring the tumor clinical outcome and the treatment response. A cell population circulating into the blood also able to form endothelial colonies in vitro and to promote vasculogenesis is represented by endothelial progenitor cells (EPCs). The number of both of these cell types is extremely low and they cannot be identified using a single marker, therefore, in absence of a definite consensus on their phenotype, require discrimination using combinations of antigens. Multiparameter flow cytometry (FCM) is ideal for rapid processing of high numbers of cells per second and is commonly utilized to quantify CECs and EPCs, however, remains technically challenging since there is as yet no standardized protocol for the identification and enumeration of these rare events. Methodology in studies on CECs and/or EPCs as clinical biomarkers in oncology is heterogeneous and data have been obtained from different studies leading to conflicting conclusions. The present review presented a critical review of the issues that limit the comparability of results of the most significant studies employing FCM for CEC and/or EPC detection in patients with cancer.

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“…Although the identification and quantification of these cells are not well standardized, they represent a promising tool for monitoring the clinical response and outcome of patients, including colon cancer patients [176,177]. However, the outcome prediction value of CECs or endothelial progenitor cells in colorectal cancer patients with or without anti-angiogenic therapy remains unclear [178].…”

Section: Microenvironment-derived Components As Liquid Biopsy Biommentioning

confidence: 99%

A Snapshot of The Tumor Microenvironment in Colorectal Cancer: The Liquid Biopsy

Herrera

Galindo-Pumariño

García-Barberán

et al. 2019

IJMS

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The molecular profile of liquid biopsies is emerging as an alternative to tissue biopsies in the clinical management of malignant diseases. In colorectal cancer, significant liquid biopsy-based biomarkers have demonstrated an ability to discriminate between asymptomatic cancer patients and healthy controls. Furthermore, this non-invasive approach appears to provide relevant information regarding the stratification of tumors with different prognoses and the monitoring of treatment responses. This review focuses on the tumor microenvironment components which are detected in blood samples of colorectal cancer patients and might represent potential biomarkers. Exosomes released by tumor and stromal cells play a major role in the modulation of cancer progression in the primary tumor microenvironment and in the formation of an inflammatory pre-metastatic niche. Stromal cells-derived exosomes are involved in driving mechanisms that promote tumor growth, migration, metastasis, and drug resistance, therefore representing substantial signaling mediators in the tumor-stroma interaction. Besides, recent findings of specifically packaged exosome cargo in Cancer-Associated Fibroblasts of colorectal cancer patients identify novel exosomal biomarkers with potential clinical applicability. Furthermore, additional different signals emitted from the tumor microenvironment and also detectable in the blood, such as soluble factors and non-tumoral circulating cells, arise as novel promising biomarkers for cancer diagnosis, prognosis, and treatment response prediction. The therapeutic potential of these factors is still limited, and studies are in their infancy. However, innovative strategies aiming at the inhibition of tumor progression by systemic exosome depletion, exosome-mediated circulating tumor cell capturing, and exosome-drug delivery systems are currently being studied and may provide considerable advantages in the near future.

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Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome

Abstract: Endothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors (VEGF and angiogenin), measured before surgery, have nothing extra to offer in predicting 2-year outcome in colorectal cancer when compared to Dukes' or AJCC stage.

Cited by 11 publications

References 36 publications

CD276-Positive Circulating Endothelial Cells Do Not Predict Response to Systemic Therapy in Advanced Colorectal Cancer

CD276-Positive Circulating Endothelial Cells Do Not Predict Response to Systemic Therapy in Advanced Colorectal Cancer

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

A Snapshot of The Tumor Microenvironment in Colorectal Cancer: The Liquid Biopsy

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