Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection

Kolenčík, Drahomír; Narayan, Sangeeta; Thiele, Jana-Aletta; McKinley, Dillon; Gerdtsson, Anna Sandström; Welter, Lisa; Hošek, Petr; Ostasov, Pavel; Vyčítal, Ondřej; Brůha, Jan; Fiala, Ondřej; Šorejs, Ondřej; Liška, Václav; Pitule, Pavel; Kühn, Peter; Shishido, Stephanie N.

doi:10.3390/cancers14030642

Cited by 4 publications

(6 citation statements)

References 37 publications

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“…Image generation, technical analysis, and rare cell detection on the slide-based HDSCA immunofluorescence technology have been described previously [ 16 , 18 , 20 , 34 ]. Briefly, stained slides are imaged at 100× magnification, and an unsupervised clustering algorithm identifies rare cells based on cellular morphology and marker expression across all 2–3 million cells per slide, as described by 761 features per cell.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we report the technical development and initial genomic and clinical validation of a new slide-based, enrichment-free immunofluorescence assay (i.e., BCMA, CD138, CD45, DAPI) for the detection of circulating rare cells and morphogenomic profiling of BCMA+ cells in PC malignancies, hereafter referred to as the “BCMA assay”. The technical methodology is built on the established “no-cell-left-behind” approach of the high-definition single-cell assay (HDSCA) workflow—previously validated clinically for various pathologies, including breast cancer [ 14 ], myocardial infarction [ 15 ], melanoma [ 15 ], prostate cancer [ 16 ], bladder cancer [ 17 ], colorectal cancer [ 18 ], and multiple myeloma [ 19 , 20 ]—and has been optimized for the detection of BCMA expression for the characterization of MM precursor cells in PC neoplasia.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

Ndacayisaba

Rappard

Shishido

et al. 2022

IJMS

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B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients’ blood could enable early disease profiling and therapy response monitoring. Here, we report the development and validation of a slide-based immunofluorescence assay (i.e., CD138, BCMA, CD45, DAPI) for enrichment-free detection, quantification, and morphogenomic characterization of BCMA-expressing cells in patients (N = 9) with plasma cell neoplasms. Varying morphological subtypes of circulating BCMA-expressing cells were detected across the CD138(+/−) and CD45(+/−) compartments, representing candidate clonotypic post-germinal center B cells, plasmablasts, and both normal and malignant plasma cells. Genomic analysis by single-cell sequencing and correlation to clinical FISH cytogenetics provides validation, with data showing that patients across the different neoplastic states carry both normal and altered BCMA-expressing cells. Furthermore, altered cells harbor cytogenetic events detected by clinical FISH. The reported enrichment-free liquid biopsy approach has potential applications as a single-cell methodology for the early detection of BCMA+ B-lymphoid malignancies and in monitoring therapy response for patients undergoing anti-BCMA treatments.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

Ndacayisaba

Rappard

Shishido

et al. 2022

IJMS

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“…Previous investigations have correlated CTC counts to CEA levels, with the two used in conjunction to accurately predict survival outcomes [13]. Generally, a higher number of CTCs indicates poorer patient outcomes in CRC [14,15], although nuances emerge when considering morphologically defined CTC subtypes and the change in cell populations over time [16,17]. With the variety of detectable biomarkers in circulation, the liquid biopsy could aid in tackling some of the clinical challenges of CRC.…”

Section: Introductionmentioning

confidence: 99%

“…However, CellSearch ® and similar systems are not commonly utilized by clinicians treating CRC [23,24]. This limited utility could be attributed to a lack of timepoint-specific standards [18] and infrequent CTC kinetics analysis, despite its clinical promise [16]. Most early-generation liquid-biopsy platforms employ enrichment-based approaches that detect a limited CTC population in the peripheral blood (PB) of CRC patients [25][26][27] and overlook other cellular subtypes with nuanced survival implications [16,28].…”

Section: Introductionmentioning

confidence: 99%

“…This limited utility could be attributed to a lack of timepoint-specific standards [18] and infrequent CTC kinetics analysis, despite its clinical promise [16]. Most early-generation liquid-biopsy platforms employ enrichment-based approaches that detect a limited CTC population in the peripheral blood (PB) of CRC patients [25][26][27] and overlook other cellular subtypes with nuanced survival implications [16,28]. In a cancer type known for its tumor heterogeneity like CRC, enrichment-based approaches limit the liquid biopsy's potential clinical utility, thereby warranting an unbiased single-cell approach that focuses on all rarity in the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

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Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility

Narayan

Courcoubetis

Mason

et al. 2022

Cancers

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Metastatic colorectal cancer (mCRC) is characterized by its extensive disease heterogeneity, suggesting that individualized analysis could be vital to improving patient outcomes. As a minimally invasive approach, the liquid biopsy has the potential to longitudinally monitor heterogeneous analytes. Current platforms primarily utilize enrichment-based approaches for epithelial-derived circulating tumor cells (CTC), but this subtype is infrequent in the peripheral blood (PB) of mCRC patients, leading to the liquid biopsy’s relative disuse in this cancer type. In this study, we evaluated 18 PB samples from 10 mCRC patients using the unbiased high-definition single-cell assay (HDSCA). We first employed a rare-event (Landscape) immunofluorescence (IF) protocol, which captured a heterogenous CTC and oncosome population, the likes of which was not observed across 50 normal donor (ND) samples. Subsequent analysis was conducted using a colorectal-targeted IF protocol to assess the frequency of CDX2-expressing CTCs and oncosomes. A multi-assay clustering analysis isolated morphologically distinct subtypes across the two IF stains, demonstrating the value of applying an unbiased single-cell approach to multiple assays in tandem. Rare-event enumerations at a single timepoint and the variation of these events over time correlated with progression-free survival. This study supports the clinical utility of an unbiased approach to interrogating the liquid biopsy in mCRC, representing the heterogeneity within the CTC classification and warranting the further molecular characterization of the rare-event analytes with clinical promise.

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Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation

Ren,

Fei,

Qiu

et al. 2024

J Exp Clin Cancer Res

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Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.

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Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection

Cited by 4 publications

References 37 publications

Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility

Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation

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