Discrimination of circulating tumor cells of breast cancer and colorectal cancer from normal human mononuclear cells using Raman spectroscopy

The role of CD47 and PD-L1 expression on circulating tumor cells (CTCs) remains unclear, and it is currently unknown whether their distribution varies between the blood and tumor tissue in breast cancer (BC). In this study, CD47 and PD-L1 expression was investigated a) on peripheral blood mononuclear cell (PBMC) cytospins from early (n = 100) and metastatic (n = 98) BC patients, by triple immunofluorescence for CD47/PD-L1/Cytokeratins, and b) on matched primary and/or metastatic tumor tissue from CTC-positive patients using immunohistochemistry. CD47+and/orPD-L1+ CTCs were detected in 11%, 16.9%, and 29.6% of early, recurrent, and de novo metastatic patients (p = 0.016). In metastatic disease, CD47highand/orPD-L1high CTCs were associated with disease progression (p = 0.005) and shorter progression-free survival (PFS) (p = 0.010), and independently predicted for an increased risk of relapse (HR: 2.719; p = 0.008) and death (HR: 2.398; p = 0.034). PD-L1 expression rates differed between CTCs and tissue tumor cells and between peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) (positive concordance of 3.8% and 4%, respectively). CD47 expression also differed between CTCs and tumor cells (positive concordance of 11.5%). In conclusion, CTCs expressing CD47 and PD-L1 have independent poor prognostic implications in metastatic BC, indicating a potential role of innate and adaptive immune evasion mechanisms in their metastatic potential. The clinical value of the parallel assessment of the peripheral and local immune response merits further evaluation in BC.

Download Full-text

Inflammation-Based Scores Increase the Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer

Cancers ◽

10.3390/cancers12051134 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1134 ◽

Cited By ~ 3

Author(s):

Svetlana Miklikova ◽

Gabriel Minarik ◽

Tatiana Sedlackova ◽

Jana Plava ◽

Marina Cihova ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Mononuclear Cells ◽

Complete Blood Count ◽

Metastatic Breast ◽

Disease Recurrence ◽

Mesenchymal Transition ◽

Lymphocyte Ratio ◽

Increased Risk

A correlation between circulating tumor cells (CTCs) and monocytes in metastatic breast cancer (BC), where CTCs and monocyte-to-lymphocyte ratio (MLR) were predictors of overall survival (OS), was recently shown. Herein, we aimed to assess the association between CTCs and the complete blood count (CBC)-derived inflammation-based scores in 284 primary BC patients. CTCs were determined in CD45-depleted peripheral blood mononuclear cells by real time-PCR. This method allowed us to detect a subset of CTCs with an epithelial-to-mesenchymal transition phenotype (CTC EMT), previously associated with inferior outcomes in primary BC. In the present study, CTC EMT positivity (hazard ratio (HR) = 2.4; 95% CI 1.20–4.66, p = 0.013) and elevated neutrophil-to-lymphocyte ratio (NLR) (HR = 2.20; 95% CI 1.07–4.55; p = 0.033) were associated with shorter progression-free survival (PFS) in primary BC patients. Multivariate analysis showed that CTC EMT-positive patients with NLR ≥ 3 had 8.6 times increased risk of disease recurrence (95% CI 2.35–31.48, p = 0.001) compared with CTC EMT-negative patients with NLR < 3. Similarly, disease recurrence was 13.14 times more likely in CTC EMT-positive patients with MLR ≥ 0.34 (95% CI 4.35–39.67, p < 0.001). Given its low methodological and financial demands, the CBC-derived inflammation-based score determination could, after broader validation, significantly improve the prognostication of BC patients.

Download Full-text

Circulating Tumor Cells and Tumor Stem Cells Detection in the Peripheral Blood Mononuclear Cells of Breast Cancer

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.21911 ◽

2016 ◽

Vol 30 (5) ◽

pp. 616-622 ◽

Cited By ~ 4

Author(s):

Feng Wang ◽

Yuan-Chun Li ◽

Li-Ping Liu ◽

Hao-Min Zhang ◽

Song Tong

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Tumor Stem Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Download Full-text

Aspirin to inhibit the formation and EMT of circulating tumor cells in patients with metastatic colorectal cancer but not breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23024 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23024-e23024

Author(s):

Chao Ni ◽

Liu Yang

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Base Line ◽

Mesenchymal Transition ◽

Clinical Trial Information

e23024 Background: High circulating tumor cells (CTCS) have been acknowledged as a poor indication in malignant disease. Besides, platelets are found play crucial role in tumor cells’ epithelial – mesenchymal transition and metastasis, so here we test if disruption of platelet function with aspirin, could decrease the number and inhibit the EMT of CTCs in metastatic colorectal (MCC) or breast cancer (MBC). Methods: Patients with MCC or MBC who were not receiving cytotoxic chemotherapy currently (except for capecitabine maintenance), while endocrine therapy, bisphosphonate or molecular targeted therapy were accepted. Base line of Platelet aggregation rate (PAR), CTCs’ number and molecular phenotype were recorded. Patients whose CTCs ≥ 5 cells/7.5ml peripheral blood were included and receive aspirin 100mg/day for the following 8 weeks. Then the phlebotomy was performed at 4, 8 weeks thereafter to obtain specimen and assess PAR, CTCs’ number and phenotype. The phenotypes of CTCs were classified into epithelial (E+), mesenchymal(M+) and middle type(express both E+ and M+ markers) with fluorescence in situ hybridization assay. Results: Forty patients (19 MBC and 21 MCC patients ) were enrolled. Base line CTC numbers were 8.7± 3.4 in MBC patients, the ratio of E+ and M+ type were 48.2 ± 22.4% and 25.1 ± 14.9% respectively; the base line CTC numbers were 10.7 ± 4.8 in MCC patients, and the ratio of E+ and M+ type were 45.3 ± 27.3% and 22.0 ± 18.5% respectively. Despite adequate platelets inhibition in both groups, CTC numbers were similar in MBC patients in the following 8 weeks ( p= 0.0532 ), while the fraction of E+ or M+ CTCs were also unchanged (E+ CTCs p= 0.305; M+ CTCs p= 0.09); however, both CTC numbers and fraction of M+CTCs were markedly decreased in MCC patients (total numbers: p< 0.01; E+ CTCs p= 0.031; M+ CTCs p= 0.013) . Conclusions: Aspirin could decreased the number of CTCs and block EMT transition in MCC patients, and our results provide potential explanation of how aspirin impede the metastasis of colorectal cancer. But this effect could not be observed in MBC patients. Future studies evaluating the underlying mechanism of this differences remain of interest, and they may be informed by our results. Clinical trial information: NCT02602938.

Download Full-text