Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells

Crook, Timothy; Leonard, Robert; Mokbel, Kefah; Thompson, Alastair; Michell, Michael; Page, Raymond; Vaid, Ashok; Mehrotra, Ravi; Ranade, Anantbhushan; Limaye, Sewanti; Patil, Darshana; Akolkar, Dadasaheb; Datta, Vineet; Fulmali, Pooja; Apurwa, Sachin; Schuster, Stefan; Srinivasan, Ajay; Datar, Rajan

doi:10.3390/cancers14143341

Cited by 25 publications

(23 citation statements)

References 43 publications

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“…Disease‐specific state‐of‐the‐art testing to completely ensure those with prostate‐associated disease (including potentially occult PCa 59 ) were excluded was not undertaken. However, the very high specificity of the assay reported in this study is consistent with other diagnostic biomarker studies 60,61 . Nevertheless, verification of the accuracy of the test in the general population requires a separate, prospective study.…”

Section: Discussionsupporting

confidence: 89%

“…However, the very high specificity of the assay reported in this study is consistent with other diagnostic biomarker studies. 60,61 Nevertheless, verification of the accuracy of the test in the general population requires a separate, prospective study. We also acknowledge that the assay was built to detect all PCas including those with low Gleason scores (i.e., 5-6).…”

Section: Discussionmentioning

confidence: 99%

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Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood

Modlin,

Kidd,

Drozdov

et al. 2024

The Prostate

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IntroductionWe describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood.Materials and MethodsWe assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27‐gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age‐matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47).ResultsA PCa‐specific 27‐gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier (“PROSTest”) was scaled 0%–100% and the industry‐standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%–95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann–Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%.ConclusionA 27‐gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood

Modlin,

Kidd,

Drozdov

et al. 2024

The Prostate

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“…Although usually scarce, the increasing number of CTCs found in the blood has been associated with poor patient prognosis, but its diagnostic and early detection potential remains largely unexplored [ 88 ]. Nonetheless, CTCs have been found in the circulation of patients with localized tumors or even prior to the detection of a primary tumor by imaging, thus indicating a putative value in early cancer detection if the right tools are applied [ 88 , 89 , 90 , 91 ].…”

Section: Multi-cancer Early Detection (Mced) Tests: State Of the Artmentioning

confidence: 99%

Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests

Brito-Rocha

Constâncio

Henrique

et al. 2023

Cells

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Cancer remains a leading cause of death worldwide, partly owing to late detection which entails limited and often ineffective therapeutic options. Most cancers lack validated screening procedures, and the ones available disclose several drawbacks, leading to low patient compliance and unnecessary workups, adding up the costs to healthcare systems. Hence, there is a great need for innovative, accurate, and minimally invasive tools for early cancer detection. In recent years, multi-cancer early detection (MCED) tests emerged as a promising screening tool, combining molecular analysis of tumor-related markers present in body fluids with artificial intelligence to simultaneously detect a variety of cancers and further discriminate the underlying cancer type. Herein, we aim to provide a highlight of the variety of strategies currently under development concerning MCED, as well as the major factors which are preventing clinical implementation. Although MCED tests depict great potential for clinical application, large-scale clinical validation studies are still lacking.

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“…To our knowledge, the test described in this manuscript is the first of its kind which uses a hallmark property of malignancy for enrichment of CGCs. Applications of this core technology for detection of breast and prostate cancers have been previously described (27,28). Our test is minimally invasive and is performed on a peripheral (venous) blood draw.…”

Section: Orthogonal Verification -Fishmentioning

confidence: 99%

Profiling of circulating glial cells allows accurate blood-based diagnosis of glial malignancies

O’Neill

Syed

Crook

et al. 2022

Preprint

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Diagnosis of primary glial malignancies (GLI-M) in individuals presenting with Intracranial Space Occupying Lesions (ICSOL) is based on histopathological evaluation (HPE) of tissue obtained by surgical resection or biopsy with attendant resource implications and risks. Approximately 70% of ICSOLs have non-malignant etiology and distinction from malignant lesions rests largely on HPE. Furthermore, GLI-M must be differentiated from metastatic lesions to the brain arising from solid tumors in other organs. We describe a blood-based test which detects GLI-M with high sensitivity and differentiates it from benign brain tumours (BBT) and brain metastases. The test is based on fluorescent multiplexed immunocytochemical (ICC) profiling for identification of Circulating Glial Cells (CGCs) and Circulating (Epithelial) Tumor Cells (CTCs) enriched from peripheral blood. The performance characteristics of the test were established in analytical validation as well as clinical studies. In an initial case-control study with discrete training (n = 31 BBT and n = 101 GLI-M) and test (n = 13 BBT and n = 44 GLI-M) sets, our platform showed 100% sensitivity and 100% specificity in identifying and differentiating GLI-M from BBT in the test set. In a prospective study of 68 individuals presenting with ICSOL, the test had 100% sensitivity and 100% specificity for identifying and differentiating GLI-M (n = 56) and BBT (n = 12). Finally, in a subset analysis of 586 samples, the test accurately identified samples from GLI-M (n = 40), BBT (n = 22), epithelial malignancies (EPI-M, n = 24) and healthy individuals (n = 500), with no false positive or false negative findings. The performance characteristics of this blood-based platform support its utility in clinical practice for diagnostic triaging of individuals presenting with ICSOL and facilitating more effective diagnosis compared to standard of care.

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Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells

Cited by 25 publications

References 43 publications

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood

Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests

Profiling of circulating glial cells allows accurate blood-based diagnosis of glial malignancies

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