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1.
Biosens Bioelectron ; 196: 113698, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34688113

RESUMO

Liquid biopsy technologies have seen a significant improvement in the last decade, offering the possibility of reliable analysis and diagnosis from several biological fluids. The use of these technologies can overcome the limits of standard clinical methods, related to invasiveness and poor patient compliance. Along with this there are now mature examples of lab-on-chips (LOC) which are available and could be an emerging and breakthrough technology for the present and near-future clinical demands that provide sample treatment, reagent addition and analysis in a sample-in/answer-out approach. The possibility of combining non-invasive liquid biopsy and LOC technologies could greatly assist in the current need for minimizing exposure and transmission risks. The recent and ongoing pandemic outbreak of SARS-CoV-2, indeed, has heavily influenced all aspects of life worldwide. Ordinary tasks have been forced to switch from "in presence" to "distanced", limiting the possibilities for a large number of activities in all fields of life outside of the home. Unfortunately, one of the settings in which physical distancing has assumed noteworthy consequences is the screening, diagnosis and follow-up of diseases. In this review, we analyse biological fluids that are easily collected without the intervention of specialized personnel and the possibility that they may be used -or not-for innovative diagnostic assays. We consider their advantages and limitations, mainly due to stability and storage and their integration into Point-of-Care diagnostics, demonstrating that technologies in some cases are mature enough to meet current clinical needs.


Assuntos
Técnicas Biossensoriais , COVID-19 , Neoplasias , Humanos , Biópsia Líquida , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Pandemias , SARS-CoV-2
2.
Cancer Lett ; 524: 91-102, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656690

RESUMO

Currently, early detection of lung cancer relies on the characterisation of images generated from computed tomography (CT). However, lung tissue biopsy, a highly invasive surgical procedure, is required to confirm CT-derived diagnostic results with very high false-positive rates. Hence, a non-invasive or minimally invasive biomarkers is essential to complement the existing low-dose CT (LDCT) for early detection, improve responses to a certain treatment, predict cancer recurrence, and to evaluate prognosis. In the past decade, liquid biopsies (e.g., blood) have been demonstrated to be highly effective for lung cancer biomarker discovery. In this review, the roles of emerging liquid biopsy-derived biomarkers such as circulating nucleic acids, circulating tumour cells (CTCs), long non-coding RNA (lncRNA), and microRNA (miRNA), as well as exosomes, have been highlighted. The advantages and limitations of these blood-based minimally invasive biomarkers have been discussed. Furthermore, the current progress of the identified biomarkers for clinical management of lung cancer has been summarised. Finally, a potential strategy for the early detection of lung cancer, using a combination of LDCT scans and well-validated biomarkers, has been discussed.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares/sangue , MicroRNAs/sangue , RNA Longo não Codificante/sangue , Biomarcadores Tumorais/sangue , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico
3.
Bull Cancer ; 108(11S): 11S46-11S54, 2021 Dec.
Artigo em Francês | MEDLINE | ID: mdl-34969515

RESUMO

The tumor biopsy remains essential for breast cancer diagnosis and characterization. Indeed, the treatment is decided according to histological subtype, and according to the presence of targetable molecular alterations. Notably, the presence of hormone receptors, ERBB2 hyperexpression or the existence of PIK3CA or ESR1 mutations are among the alterations commonly investigated. But these biological characteristics are determined only partially by tumor biopsy, due to tumor heterogeneity or tumor plasticity that happens spontaneously or under treatment. Liquid biopsy, and in particular circulating tumor DNA and circulating tumor cells, is a non-invasive method to identify and characterize the presence of cancer in the blood. The aim of this review is to determine the value of liquid biopsy to enhance or replace the data provided by a tumor biopsy.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA Tumoral Circulante/sangue , Biópsia Líquida , Neoplasias da Mama/sangue , Neoplasias da Mama/química , Classe I de Fosfatidilinositol 3-Quinases/genética , Receptor alfa de Estrogênio/genética , Feminino , Amplificação de Genes , Genes erbB-2 , Humanos , Mutação , Células Neoplásicas Circulantes/patologia , Receptor ErbB-2/análise
4.
Ann Oncol ; 32(12): 1472-1474, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34815016
5.
BMC Cancer ; 21(1): 1075, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600526

RESUMO

BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/radioterapia , Ácidos Nucleicos Livres/sangue , Neoplasias Bucais/sangue , Neoplasias Bucais/radioterapia , Animais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/induzido quimicamente , DNA Tumoral Circulante/sangue , Papillomavirus de Coelho Cottontail , Molécula de Adesão da Célula Epitelial/sangue , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Neoplasias de Cabeça e Pescoço/radioterapia , Separação Imunomagnética/métodos , Biópsia Líquida/métodos , Masculino , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/virologia , Nanopartículas , Transplante de Neoplasias , Fases de Leitura Aberta , Coelhos , Dosagem Radioterapêutica , Carga Tumoral
6.
J Coll Physicians Surg Pak ; 31(10): 1174-1178, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34601837

RESUMO

OBJECTIVE: To detect the Kras gene through liquid biopsy, a less invasive technique in diagnosed colorectal cancer patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Oncology, Dr. Ziauddin Hospital and Bait-us-Sukoon Cancer Hospital, Karachi, from 2019 to 2020. METHODOLOGY: Circulating tumor DNA (ctDNA) in colorectal cancer patients was extracted through magnetic bead technique using MagMAX cell free DNA kit (Thermofisher, Uk). The frequency of Kras gene was quantified using a real-time polymerase chain reaction (RT-PCR) assay (qPCR). ANOVA and Chi-square tests were utilised for statistical analysis. RESULTS: Mean threshold cycle (CT) of Kras gene showed significantly higher expression 15.6 ± 1.82 (p=0.001) in stage IV CRC cases compared to early stages (19.53 ± 18.223.7 ± 2.9 and 19.8 ± 2.69 of stage 1, 2 and 3, respectively. Similarly, ΔCT mean of Kras gene at stage IV showed significantly higher expression of 2.48 ± 1.40 (0.048), compared to 2.39 ± 0.6, 3.12 ± 0.68 and 3.15 ± 0.41 of stage 1, 2 and 3, respectively. Males (n=40, 55%) showed significant association (p=0.001) with CRC compared to females (n=33, 45%). Categorisation of tumor types within different age groups revealed that colon cancer was more frequent (n=11, 15.1%) in the 41-50 age group, while rectal cancer was more frequent (n= 11, 15.1%) in the 41-50 age group, while rectal cancer was more in the 51-60 age group (n=11, 15.1%). CONCLUSION: Kras gene was detected with significantly increased levels in plasma of CRC patients at advanced stages. This confirms that liquid biopsy can be used to detect Kras gene in ctDNA of CRC patients through a magnetic bead based technique. Key Words: Liquid biopsy, Circulating tumor DNA, KRAS, Colorectal cancer, Real-time polymerase chain reaction.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Colorretais/genética , Análise Custo-Benefício , Estudos Transversais , Feminino , Humanos , Biópsia Líquida , Masculino , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética
7.
BMC Cancer ; 21(1): 1092, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34627187

RESUMO

BACKGROUND: In oncology, liquid biopsy is of major relevance from theranostic point of view. The searching for mutations in circulating tumor DNA (ctDNA) in case of colorectal cancers (CRCs) allows the optimization of patient care. In this context, independent of mutation status biomarkers are required for its detection to confirm the presence of ctDNA in liquid biopsies. Indeed, the hypermethylation of NPY and WIF1 genes appear to be an ideal biomarker for the specific detection of ctDNA in CRCs. The objective of this work is to develop the research of hypermethylation of NPY and WIF1 by Crystal Digital PCR™ for the detection of ctDNA in CRCs. METHODS: Detection of hypermethylated NPY and WIF1 was developed on Cristal digital PCR™. Biological validation was performed from a local cohort of 22 liquid biopsies and 23 tissue samples from patients with CRC. These patients were treated at the University Hospital of Besancon (France). RESULTS: The local cohort study confirmed that NPY and WIF1 were significantly hypermethylated in tumor tissues compared to adjacent non-tumor tissues (WIF1 p < 0.001; NPY p < 0.001; non-parametric Wilcoxon paired-series test). Histological characteristics, tumor stages or mutation status were not correlated to the methylation profiles. On the other hand, hypermethylation of NPY or WIF1 in liquid biopsy had a 95.5% [95%CI 77-100%] sensitivity and 100% [95%CI 69-100%] specificity. CONCLUSION: Using Crystal digital PCR™, this study shows that hypermethylation of NPY and WIF1 are constant specific biomarkers of CRCs regardless of a potential role in carcinogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , DNA Tumoral Circulante/genética , Neoplasias Colorretais/genética , Metilação de DNA , Neuropeptídeo Y/genética , Reação em Cadeia da Polimerase/métodos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Tumoral Circulante/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Intervalos de Confiança , Feminino , Marcadores Genéticos , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Neuropeptídeo Y/metabolismo , Sensibilidade e Especificidade
9.
World J Gastroenterol ; 27(34): 5666-5681, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34629793

RESUMO

Gastrointestinal (GI) cancers are among the most common cancer types and leading causes of cancer-related deaths worldwide. There is a tremendous clinical need for effective early diagnosis for better healthcare of GI cancer patients. In this article, we provide a short overview of the recent advances in GI cancer diagnosis. In the first part, we discuss the applications of blood-based biomarkers, such as plasma circulating cell-free DNA, circulating tumor cells, extracellular vesicles, and circulating cell-free RNA, for cancer liquid biopsies. In the second part, we review the current trends of artificial intelligence (AI) for pathology image and tissue biopsy analysis for GI cancer, as well as deep learning-based approaches for purity assessment of tissue biopsies. We further provide our opinions on the future directions in blood-based and AI-enhanced approaches for GI cancer diagnosis, and we think that these fields will have more intensive integrations with clinical needs in the near future.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Gastrointestinais , Inteligência Artificial , Detecção Precoce de Câncer , Neoplasias Gastrointestinais/diagnóstico , Humanos , Biópsia Líquida
10.
Crit Rev Oncol Hematol ; 167: 103495, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34655743

RESUMO

Extracellular vesicles (EV) are cell-derived lipid bilayer-delimited structures providing an important means of intercellular communication. Recent studies have shown that EV, particularly exosomes and large-oncosomes contain miRNA and proteins crucial in prostate cancer (PCa) progression, metastasis and treatment resistance. This includes not just EV released from PCa cells, but also from other cells in the tumor microenvironment. PCa patient derived EV have a unique composition compared to healthy and benign prostatic diseases. As such, EV show promise as diagnostic liquid biopsy biomarkers, both as an adjunct and alternative to the invasive current gold-standard. EV could also be utilized to stratify patients' risk and predict response to hormonal, chemo, immune- and targeted therapy, which will direct future treatment decisions in PCa. We present a summary of the current evidence on the role of EV in PCa and the application of EV in PCa diagnosis and treatment to optimize patient outcomes.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Neoplasias da Próstata , Humanos , Biópsia Líquida , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Microambiente Tumoral
11.
Gan To Kagaku Ryoho ; 48(10): 1197-1202, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657047

RESUMO

With the development of cancer biology and treatment, it has become essential to search not only for basic information such as histology but also for biomarkers that represent the characteristics of tumors when deciding on a treatment strategy. Circulating tumor cells(CTCs), circulating tumor DNA(ctDNA), exosomes, and microRNAs are present in the blood or other body fluid and reflect the tumor status in real-time. Since liquid biopsy is less invasive and easier to collect, it is almost ready to be applied not only for diagnosis but also for monitoring the acquisition of resistance to treatment in real-time. The number of CTCs has been shown to be a prognostic factor in itself for breast cancer, and ctDNA with whole-genome sequencing of tissue specimens is developed to monitor recurrence using the individualized ctDNA set for each patient. Furthermore, cancer genome profiling tests using ctDNA have been commercialized and can now be used with an insurance reimbursement. The possibility of early diagnosis using blood microRNA has already been reported, and the sensitivity and specificity are currently being verified in a prospective observational with a screening cohort. The liquid biopsy will be essential for future breast cancer treatment.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , MicroRNAs , Células Neoplásicas Circulantes , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Biópsia Líquida , MicroRNAs/genética , Recidiva Local de Neoplasia
12.
Gan To Kagaku Ryoho ; 48(10): 1203-1208, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657048

RESUMO

With increasing treatment options for metastatic prostate cancer(mPC), there is a growing attention to circulating tumor cells(CTC)and circulating tumor DNA(ctDNA)as minimally invasive biomarkers to facilitate precision medicine. CTC count and ctDNA abundance have been reported to be prognostic factors. In addition, on-treatment changes in these values might also be associated with the treatment response. Androgen receptor gene alterations, including ligand-binding domain mutations, copy number amplification, or structural rearrangements, are identified in most metastatic castration-resistant prostate cancer(mCRPC)and associated with treatment response to androgen receptor pathway inhibitors. Alterations in different DNA damage repair genes, including BRCA2, ATM, CDK12, or mismatch repair genes, are linked to favorable response to targeted therapies such as poly(adenosine diphosphate-ribose)polymerase(PARP)inhibitors or immune checkpoint inhibitors. Overactivation of the PI3K signaling pathway is mainly caused by PTEN loss, and several clinical trials are underway to assess the treatment effect of the targeted therapies such as Akt inhibitors. To disseminate treatment strategies using CTC and ctDNA in clinical practice, we will require prospective biomarker-driven clinical trials, development of novel targeted therapies, and exploration of other molecular characteristics such as epigenome.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Biomarcadores , Biomarcadores Tumorais/genética , Humanos , Biópsia Líquida , Masculino , Fosfatidilinositol 3-Quinases , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética
13.
Gan To Kagaku Ryoho ; 48(10): 1209-1213, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657049

RESUMO

In recent years, sequencing of circulating tumor DNA(ctDNA)in peripheral blood has emerged as a promising non-invasive approach for diagnosis, genotyping, risk stratification, response monitoring, and the detection of actionable mutations in malignant lymphomas. Current available technologies for ctDNA detection are polymerase chain reaction-based methods and next generation sequencing techniques. They target single nucleotide variants, structural variants, copy number alterations, and immunoglobulin heavy chain gene/T-cell receptor gene rearrangement, which are specific to lymphomas. Non- invasive detection of ctDNA cannot replace conventional tumor tissue biopsies for initial diagnosis of lymphomas because histological architecture is important. However, it may be an effective tool in certain extranodal lymphomas, such as intravascular large B-cell lymphoma(IVLBCL)and primary diffuse large B-cell lymphoma of the nervous system lymphoma(PCNSL). Tumor cells proliferate in lumina of small vessels, and usually do not form obvious mass to biopsy in IVLBCL. Both lymphomas share genetic mutations including MYD88 L265P, CD79B, and genetic aberrations favoring immune escape. Therefore detection of these mutations via ctDNA analysis could be helpful for prompt diagnosis of IVLBCL and PCNSL. In addition to the fact that ctDNA contains spatial tumor heterogeneity, which may allow for more accurate assessment of prognostic factors and tracking of treatment-resistant subclones, liquid biopsy can be considered a timely snapshot of the disease burden because it can be performed continuously. Since the genomic abnormalities frequently observed in hematologic malignancies are different from those in solid tumors, it is necessary to develop a unique gene panel test. In Japan, preparations are underway to establish a system for genomic and precision medicine for hematologic malignancies.


Assuntos
DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Biomarcadores Tumorais , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Mutação
14.
Med Hypotheses ; 156: 110682, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34598097

RESUMO

Recognition of low grade or asymptomatic systemic diseases suggests prevention of the worst, yet has been proven challenging ever since. Biomarker-based liquid biopsy has emerged in recent years as a practical platform for the assessment of systemic diseases yet, technical realizations were mainly focused on cancer, faced challenges in accuracy at early stage and are lacking provision of sufficient evidence of disease. In particular in cell-based cancer liquid biopsy, obstacles are rarity and heterogeneity of circulating tumor and tumor-associated rare cells. Evidence is mounting about an entire spectrum of distinct circulating rare cell types that denotes the systemic component of a certain physiological state. Therefore, circulating rare cells in combination may arise from yet, also account for systemic diseases, which we denote as multi-rare cell association and involves foremost bone marrow-derived progenitor and stem cells yet, also matured somatic cell types. One would expect immense diagnostic value in the read-out of the so called rare cell population which represents cytological evidence of abnormality. We hypothesize that comprehensive rare cell population profiling as contrasted to the biomarker screening approach may realize the premise of a biopsy as to confirm, characterize, grade, stage or predict a systemic disease. This novel approach represents the "missing link" in diagnostic care of in particular early or residual systemic disease and presumes a steady gain in knowledge about the clinical interpretation of rare cell population profiles thus, expecting the knowledge-driven transformation of cell-based liquid biopsy from suggestion to confirmation. We support our hypothesis by past findings made by others and us and provide insights how to interpret a certain rare cell population profile.


Assuntos
Neoplasias , Biomarcadores , Biomarcadores Tumorais , Biópsia , Humanos , Biópsia Líquida , Neoplasias/diagnóstico
15.
Ann Oncol ; 32(12): 1608-1617, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34690007

RESUMO

BACKGROUND: In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with reactivation of telomerase or alternative lengthening of telomeres (ALT), respectively, i.e. the two telomere maintenance mechanisms (TMM). Strangely, 25% of gliomas have been reported to display neither or both of these alterations. MATERIALS AND METHODS: The C-circle (CC) assay was adapted to tumor (formalin-fixed paraffin-embedded and frozen) and blood samples to investigate the TMM. RESULTS: We constructed a CC-based algorithm able to identify the TMM and reported a sensitivity of 100% and a specificity of 97.3% (n = 284 gliomas). By combining the TMM, the mutational status of the isocitrate dehydrogenase 1/2 (IDH) gene (IDHmt), and the histological grading, we propose a new classification tool: TeloDIAG. This classification defined five subtypes: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low-grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma (GBM), respectively; the last class gathers ALT+ IDHwt gliomas that tend to be related to longer survival (21.2 months) than tGBM (16.5 months). The TeloDIAG was 99% concordant with the World Health Organization classification (n = 312), and further modified the classification of 55 of 144 (38%) gliomas with atypical molecular characteristics. As an example, 14 of 69 (20%) of TERTwt, ATRXwt, and IDHwt GBM were actually tAIV. Outstandingly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 97% (n = 206 gliomas and 30 healthy donors). CONCLUSION: The TeloDIAG is a new, simple, and effective tool helping in glioma diagnosis and a promising option for liquid biopsy.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Biópsia Líquida , Telômero/genética , Proteína Nuclear Ligada ao X/genética
16.
Analyst ; 146(23): 7048-7069, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34709247

RESUMO

Circulating tumor cell (CTC) analysis as a liquid biopsy can be used for early diagnosis of cancer, evaluating cancer progression, and assessing treatment efficacy. The enrichment of CTCs from patient blood is important for CTC analysis due to the extreme rarity of CTCs. This paper updates recent advances in CTC enrichment methods. We first review single-modality methods, including biophysical and biochemical methods. Hybrid-modality methods, combining at least two single-modality methods, are gaining increasing popularity for their improved performance. Then this paper reviews hybrid-modality methods, which are categorized into integrated and sequenced hybrid-modality methods. The state of the art indicates that the CTC capture efficiencies of integrated hybrid-modality methods can reach 85% or higher by taking advantage of the superimposed and enhanced capture effects from multiple single-modality methods. Moreover, a hybrid method integrating biophysical with biochemical methods is characterized by both high processing rate and high specificity.


Assuntos
Células Neoplásicas Circulantes , Contagem de Células , Humanos , Biópsia Líquida
17.
Elife ; 102021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34696827

RESUMO

Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals. Focusing on breast, bladder, prostate, and lung cancer, we find that infrared molecular fingerprinting is capable of detecting cancer: training a support vector machine algorithm allowed us to obtain binary classification performance in the range of 0.78-0.89 (area under the receiver operating characteristic curve [AUC]), with a clear correlation between AUC and tumour load. Intriguingly, we find that the spectral signatures differ between different cancer types. This study lays the foundation for high-throughput onco-IR-phenotyping of four common cancers, providing a cost-effective, complementary analytical tool for disease recognition.


Assuntos
Neoplasias da Mama/diagnóstico , Biópsia Líquida/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias da Próstata/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Humanos , Aprendizado de Máquina , Masculino
18.
Am J Physiol Cell Physiol ; 321(5): C779-C797, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34495763

RESUMO

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their noninvasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Detecção Precoce de Câncer , Vesículas Extracelulares/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Vesículas Extracelulares/patologia , Feminino , Humanos , Biópsia Líquida , Valor Preditivo dos Testes , Prognóstico , Proteômica
19.
J Vis Exp ; (175)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34570090

RESUMO

There is significant potential clinical utility for the application of a liquid biopsy platform for retinoblastoma, given that direct tumor biopsy is prohibited in these patients. The aqueous humor (AH) forms in a separate compartment from the tumor but is enclosed within the same ocular space. Thus, it is an enriched source of eye-specific tumoral genomic information that can be used as a liquid biopsy or surrogate to tumor biopsy for this disease. This manuscript details a methodology for safely extracting the AH from retinoblastoma eyes via clear corneal paracentesis. Additionally, the steps for genomic analysis, including cell-free DNA isolation and purification, next-generation sequencing, somatic copy number alteration (SCNA) analysis, RB1 single nucleotide variant (SNV) mutation identification, and tumor fraction estimation are presented. The pre-analytical, analytical, and early clinical validity of the AH liquid biopsy platform have been evaluated; however, it is not without limitations. These are largely a consequence of the quantity of cell-free DNA that is required for certain steps of the assay. Compared to other blood-based liquid biopsy platforms currently under investigation for retinoblastoma, an AH-based platform is limited by the volume of biofluid (and thus the quantity of DNA) that can be extracted from the eye; the benefit is that AH is eye-specific. The platform discussed here is unique in that it detects circulating tumor DNA in the AH via two mechanisms (SCNAs and RB1 SNVs), yielding a higher sensitivity for identifying tumoral genomic information. The AH liquid biopsy has the potential for direct clinical application to precision oncology for retinoblastoma patients, with particular importance for patients with bilateral disease as the AH is specific to the tumors in each eye. There is ongoing research with applications of this platform to patients with other ocular tumors as well.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humor Aquoso , Genômica , Humanos , Biópsia Líquida , Paracentese , Medicina de Precisão , Neoplasias da Retina/genética , Retinoblastoma/genética
20.
Cancer J ; 27(5): 404-409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570455

RESUMO

ABSTRACT: Liquid biopsy approaches for detection of circulating biomarkers of cancer have been utilized in oncology in many clinical settings from early detection to disease monitoring. Recent approaches have focused on circulating tumor cells, circulating tumor DNA, and circulating RNAs in a variety of biofluids. However, very little progress has been made in implementing such approaches for detection of brain tumors, despite the tremendous clinical need for earlier and less invasive diagnosis, as well as more accurate assessment of disease status. In this review, we highlight the recent methodological improvements in the field of liquid biopsy technologies specifically for glioblastoma. Although many retrospective and few prospective studies have been conducted to assess the utility of circulating biomarkers for detection of brain tumors, none have yet moved forward to clinical implementation.


Assuntos
Glioblastoma , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Glioblastoma/diagnóstico , Humanos , Biópsia Líquida , Estudos Prospectivos , Estudos Retrospectivos
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