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1.
Sci Rep ; 14(1): 5841, 2024 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-38462648

RESUMO

Cancer presents a significant global health burden, resulting in millions of annual deaths. Timely detection is critical for improving survival rates, offering a crucial window for timely medical interventions. Liquid biopsy, analyzing genetic variations, and mutations in circulating cell-free, circulating tumor DNA (cfDNA/ctDNA) or molecular biomarkers, has emerged as a tool for early detection. This study focuses on cancer detection using mutations in plasma cfDNA/ctDNA and protein biomarker concentrations. The proposed system initially calculates the correlation coefficient to identify correlated features, while mutual information assesses each feature's relevance to the target variable, eliminating redundant features to improve efficiency. The eXtrem Gradient Boosting (XGBoost) feature importance method iteratively selects the top ten features, resulting in a 60% dataset dimensionality reduction. The Light Gradient Boosting Machine (LGBM) model is employed for classification, optimizing its performance through a random search for hyper-parameters. Final predictions are obtained by ensembling LGBM models from tenfold cross-validation, weighted by their respective balanced accuracy, and averaged to get final predictions. Applying this methodology, the proposed system achieves 99.45% accuracy and 99.95% AUC for detecting the presence of cancer while achieving 93.94% accuracy and 97.81% AUC for cancer-type classification. Our methodology leads to enhanced healthcare outcomes for cancer patients.


Assuntos
Ácidos Nucleicos Livres , Neoplasias , Humanos , Biópsia Líquida/métodos , Ácidos Nucleicos Livres/genética , Neoplasias/diagnóstico , Neoplasias/genética , DNA de Neoplasias , Aprendizado de Máquina
2.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473864

RESUMO

Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including exosomes, are integral to carcinogenesis, and are found in NMSC releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived EVs remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. This systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived EVs, their molecular cargo, and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA have emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are being actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias Cutâneas , Humanos , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Biópsia Líquida , Neoplasias Cutâneas/patologia , Biomarcadores/metabolismo
3.
Int J Mol Sci ; 25(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38473908

RESUMO

As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management.


Assuntos
Ácidos Nucleicos Livres , Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Células Neoplásicas Circulantes , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia Líquida/métodos , Vesículas Extracelulares/metabolismo , Ácidos Nucleicos Livres/metabolismo , Células Neoplásicas Circulantes/patologia
4.
Zhongguo Fei Ai Za Zhi ; 27(2): 126-132, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38453444

RESUMO

Liquid biopsy is gradually being applied in the clinical diagnosis and treatment of lung cancer. At present, with the development of metabolomics, more and more metabolic biomarkers are considered as potential sensitive markers reflecting the occurrence and development of tumors. This article summarizes the changes in the main metabolic pathways of lung cancer, including glucose metabolism, amino acid metabolism, lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and purine metabolism. Meanwhile, this article reviews the role of metabolic biomarkers in the early diagnosis of lung cancer, predicting disease progression, and evaluating the efficacy of chemotherapy and immunotherapy, aiming to provide effective biomarkers for tumor diagnosis and treatment.
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Assuntos
Biomarcadores Tumorais , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Metabolômica , Redes e Vias Metabólicas , Biópsia Líquida
5.
Theranostics ; 14(5): 1966-1981, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505618

RESUMO

Exosomes, carrying distinctive biomolecules reflective of their parent cell's status and origin, show promise as liquid biopsy biomarkers for cancer diagnosis. However, their clinical translation remains challenging due to their relatively low concentration in body fluids. Surface-Enhanced Raman spectroscopy (SERS) has recently gained significant attention as a label-free and sensitive technique for exosome analysis. This review explores label-free SERS for exosome detection, covering exosome isolation and characterization methods, advancements in SERS substrates, and fingerprint analysis techniques using machine learning. Furthermore, we emphasize the challenges and offer insights into the future prospects of SERS-based exosome analysis to enhance cancer diagnosis.


Assuntos
Exossomos , Neoplasias , Humanos , Exossomos/química , Análise Espectral Raman/métodos , Biomarcadores/análise , Biópsia Líquida/métodos , Neoplasias/diagnóstico
6.
JCI Insight ; 9(6)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38516891

RESUMO

BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV+ OPSCC.ConclusionOur data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.FundingNIH grants R33 CA229023, R21 CA225493; NIH/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Estados Unidos , Humanos , Infecções por Papillomavirus/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , DNA de Neoplasias , Biópsia Líquida
7.
Tumour Biol ; 46(s1): S1-S7, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517827

RESUMO

Blood-based diagnostics for lung cancer support the diagnosis, estimation of prognosis, prediction, and monitoring of therapy response in lung cancer patients. The clinical utility of serum tumor markers has considerably increased due to developments in serum protein tumor markers analytics and clinical biomarker studies, the exploration of preanalytical and influencing conditions, the interpretation of biomarker combinations and individual biomarker kinetics, as well as the implementation of biostatistical models. In addition, circulating tumor DNA (ctDNA) and other liquid biopsy markers are playing an increasingly prominent role in the molecular tumor characterization and the monitoring of tumor evolution over time. Thus, modern lung cancer biomarkers may considerably contribute to an individualized companion diagnostics and provide a sensitive guidance for patients throughout the course of their disease. In this special edition on Tumor Markers in Lung Cancer, experts summarize recent developments in clinical laboratory diagnostics of lung cancer and give an outlook on future challenges and opportunities.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Biomarcadores Tumorais/genética , Biópsia Líquida , DNA de Neoplasias/genética , Pulmão/patologia
8.
Adv Clin Chem ; 119: 33-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38514211

RESUMO

Minimal residual disease (MRD) has been defined as a very small numbers of cancer cells that remain in the body after curative treatment. Its presence or absence will ultimately determine prognosis. With the introduction of new technologies the presence of MRD in patients with solid tumours can be detected and characterized. As MRD predicts future relapse, be it early or late treatment failure, in an otherwise asymptomatic patient its treatment and when to start treatment remains to be determined. Thus the concepts of personalized medicine using different biomarkers to classify the biological properties of MRD maybe come possible. Based on this determinations it may be possible to use targeted therapies rather than all patients with the same type of cancer receiving a standard treatment. However, it is important to understand the limitations of the different technologies, what these techniques are detecting and how they may help in the treatment of patients with cancer. The majority of published studies are in patients with metastatic cancer and there are few reports in patients with MRD. In this chapter the concept of MRD, the methods used to detect it and what treatments may be effective based on the biological characteristics of the tumour cells as determined by different biomarkers is reviewed. MRD depends on the phenotypic properties of the tumour cells to survive in their new environment and the anti-tumour immune response. This is a dynamic process and changes with time in the wake of immunosuppression caused by the tumour cells and/or the effects of treatment to select resistant tumour cells. With the use of biomarkers to typify the characteristics of MRD and the development of new drugs a personalized treatment can be designed rather than all patients given the same treatment. Patients who are initially negative for MRD may not require further treatment with liquid biopsies used to monitor the patients during follow-up in order to detect those patients who may become MRD positive. The liquid biopsy used during the follow up of MRD positive patients can be used to detect changes in the biological properties of the tumour cells and thus may need treatment changes to overcome tumour cell resistance.


Assuntos
Biomarcadores Tumorais , Medicina de Precisão , Humanos , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Prognóstico , Biomarcadores , Biópsia Líquida
9.
Semin Radiat Oncol ; 34(2): 195-206, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508784

RESUMO

Due to their rarity and complexity, sarcomas represent a substantial therapeutic challenge. However, the incredible diversity within and across sarcoma subtypes presents an opportunity for personalized care to maximize efficacy and limit toxicity. A deeper understanding of the molecular alterations that drive sarcoma development and treatment response has paved the way for molecular biomarkers to shape sarcoma treatment. Genetic, transcriptomic, and protein biomarkers have become critical tools for diagnosis, prognostication, and treatment selection in patients with sarcomas. In the future, emerging biomarkers like circulating tumor DNA analysis offer the potential to improve early detection, monitoring response to treatment, and identifying mechanisms of resistance to personalize sarcoma treatment. Here, we review the current state of molecular biomarkers for sarcomas and highlight opportunities and challenges for the implementation of new technologies in the future.


Assuntos
Biomarcadores Tumorais , Sarcoma , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Sarcoma/genética , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Biópsia Líquida , Previsões
10.
J Hematol Oncol ; 17(1): 12, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515194

RESUMO

Cancer early detection and treatment response prediction continue to pose significant challenges. Cancer liquid biopsies focusing on detecting circulating tumor cells (CTCs) and DNA (ctDNA) have shown enormous potential due to their non-invasive nature and the implications in precision cancer management. Recently, liquid biopsy has been further expanded to profile glycoproteins, which are the products of post-translational modifications of proteins and play key roles in both normal and pathological processes, including cancers. The advancements in chemical and mass spectrometry-based technologies and artificial intelligence-based platforms have enabled extensive studies of cancer and organ-specific changes in glycans and glycoproteins through glycomics and glycoproteomics. Glycoproteomic analysis has emerged as a promising tool for biomarker discovery and development in early detection of cancers and prediction of treatment efficacy including response to immunotherapies. These biomarkers could play a crucial role in aiding in early intervention and personalized therapy decisions. In this review, we summarize the significant advance in cancer glycoproteomic biomarker studies and the promise and challenges in integration into clinical practice to improve cancer patient care.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Neoplasias/diagnóstico , Biomarcadores Tumorais/análise , Glicoproteínas/análise , Glicoproteínas/metabolismo , Biópsia Líquida , Proteoma
11.
J Hematol Oncol ; 17(1): 10, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486294

RESUMO

Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques. Optical biosensors based on nanomaterials open an important opportunity in liquid biopsy because of their enhanced sensing performance with simple and practical properties. In this review article, we summarized recent innovations in optical nanomaterials to demonstrate the sensitive detection of protein, peptide, ctDNA, miRNA, exosome, and CTCs. Each study prepares the optical nanomaterials with a tailored design to enhance the sensing performance and to meet the requirements of each biomarker. The unique optical characteristics of metallic nanoparticles (NPs), quantum dots, upconversion NPs, silica NPs, polymeric NPs, and carbon nanomaterials are exploited for sensitive detection mechanisms. These recent advances in liquid biopsy using optical nanomaterials give us an opportunity to overcome challenging issues and provide a resource for understanding the unknown characteristics of the biomarkers as well as the mechanism of the disease.


Assuntos
MicroRNAs , Nanoestruturas , Humanos , Biomarcadores , Biópsia Líquida , Biópsia
12.
Front Biosci (Landmark Ed) ; 29(2): 80, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38420812

RESUMO

The incidence and mortality from malignant tumors continue to rise each year. Consequently, early diagnosis and intervention are vital for improving patient' prognosis and survival. The traditional pathological tissue biopsy is currently considered the gold standard for cancer diagnosis. However, it suffers from several limitations including invasiveness, sometimes not repeatable or unsuitable, and the inability to capture the dynamic nature of tumors in terms of space and time. Consequently, these limit the application of tissue biopsies for the diagnosis of early-stage tumors and have redirected the research focus towards liquid biopsies. Blood-based liquid biopsies have thus emerged as a promising option for non-invasive assessment of tumor-specific biomarkers. These minimally invasive, easily accessible, and reproducible tests offer several advantages, such as being mostly complication-free and efficient at monitoring tumor progression and tracing drug resistance. Liquid biopsies show great potential for cancer prediction, diagnosis, and prognostic assessment. Circulating tumor-educated platelets (TEPs) possess the unique ability to absorb nucleic acids from the bloodstream and to modify transcripts derived from megakaryocytes in response to external signals. In addition, circulating free RNA (cfRNA) constitutes a significant portion of the biomolecules present in the bloodstream. This paper aims to provide a comprehensive overview of the current research status regarding TEP RNA and cfRNA in liquid biopsies from various tumor types. Our analysis includes cancers of the lung, liver, pancreas, breast, nasopharynx, ovary and colon, as well as multiple myeloma and sarcoma. By synthesizing this information, we intend to establish a solid theoretical foundation for exploring potential applications of circulating RNA as a reliable biomarker for tumor diagnosis and monitoring.


Assuntos
Ácidos Nucleicos Livres , Neoplasias , Células Neoplásicas Circulantes , Feminino , Humanos , Ácidos Nucleicos Livres/genética , Biópsia Líquida , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , RNA/genética , RNA Neoplásico , Biomarcadores Tumorais/genética , Células Neoplásicas Circulantes/patologia
13.
Pharmacol Rev ; 76(2): 199-227, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351075

RESUMO

Extracellular vesicles (EVs) have emerged as an attractive liquid biopsy approach in the diagnosis and prognosis of multiple diseases and disorders. The feasibility of enriching specific subpopulations of EVs from biofluids based on their unique surface markers has opened novel opportunities to gain molecular insight from various tissues and organs, including the brain. Over the past decade, EVs in bodily fluids have been extensively studied for biomarkers associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorders, substance use disorders, human immunodeficiency virus-associated neurocognitive disorder, and cancer/treatment-induced neurodegeneration. These studies have focused on the isolation and cargo characterization of either total EVs or brain cells, such as neuron-, astrocyte-, microglia-, oligodendrocyte-, pericyte-, and endothelial-derived EVs from biofluids to achieve early diagnosis and molecular characterization and to predict the treatment and intervention outcomes. The findings of these studies have demonstrated that EVs could serve as a repetitive and less invasive source of valuable molecular information for these neurological disorders, supplementing existing costly neuroimaging techniques and relatively invasive measures, like lumbar puncture. However, the initial excitement surrounding blood-based biomarkers for brain-related diseases has been tempered by challenges, such as lack of central nervous system specificity in EV markers, lengthy protocols, and the absence of standardized procedures for biological sample collection, EV isolation, and characterization. Nevertheless, with rapid advancements in the EV field, supported by improved isolation methods and sensitive assays for cargo characterization, brain cell-derived EVs continue to offer unparallel opportunities with significant translational implications for various neurological disorders. SIGNIFICANCE STATEMENT: Extracellular vesicles present a less invasive liquid biopsy approach in the diagnosis and prognosis of various neurological disorders. Characterizing these vesicles in biofluids holds the potential to yield valuable molecular information, thereby significantly impacting the development of novel biomarkers for various neurological disorders. This paper has reviewed the methodology employed to isolate extracellular vesicles derived from various brain cells in biofluids, their utility in enhancing the molecular understanding of neurodegeneration, and the potential challenges in this research field.


Assuntos
Doença de Alzheimer , Transtorno Depressivo Maior , Vesículas Extracelulares , Humanos , Transtorno Depressivo Maior/patologia , Vesículas Extracelulares/patologia , Biópsia Líquida , Biomarcadores
14.
Nat Commun ; 15(1): 1828, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418825

RESUMO

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Prognóstico , Estudos Prospectivos , Bancos de Espécimes Biológicos , Biomarcadores Tumorais/genética , Biópsia Líquida , Mutação
15.
Mol Cancer ; 23(1): 28, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308296

RESUMO

BACKGROUND: Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. METHODS: Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing. RESULTS: The hybridization and capture panel, covering around 74 kb in total, was applied to sequence a cohort of 25 PBCs, 25 pancreatitis patients, 25 clinical controls, and seven cases of Intraductal Papillary Mucinous Neoplasia (IPMN). An unbiased machine learning approach identified the 50 most discriminatory methylation markers for the discrimination of PBC from pancreatitis and controls resulting in an AUROC of 0.85 and 0.88 for a training (n = 45) and a validation (n = 37) data set, respectively. The panel was also able to distinguish high grade from low grade IPMN samples. CONCLUSIONS: We present a proof of concept for a methylation biomarker panel with better performance and improved discriminatory power than the current clinical marker CA19-9 for the discrimination of pancreato-biliary cancers from non-cancerous pancreatitis patients and clinical controls. This workflow might be used in future diagnostics for the detection of precancerous lesions, e.g. the identification of high grade IPMNs vs. low grade IPMNs.


Assuntos
Carcinoma Ductal Pancreático , Ácidos Nucleicos Livres , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Pancreatite , Humanos , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Pancreatite/diagnóstico , Pancreatite/genética , Biópsia Líquida , Carcinoma Ductal Pancreático/patologia
16.
Mol Cancer ; 23(1): 36, 2024 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-38365716

RESUMO

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Células T , Humanos , Reprodutibilidade dos Testes , Biomarcadores Tumorais/genética , Herpesvirus Humano 4 , Biópsia Líquida/métodos , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética
17.
J Transl Med ; 22(1): 132, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310289

RESUMO

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Fosfatidilinositol 3-Quinases/genética , Avaliação Pré-Clínica de Medicamentos , Proteínas Proto-Oncogênicas p21(ras)/genética , Detecção Precoce de Câncer , Biópsia Líquida , Inibidores de Fosfoinositídeo-3 Quinase , Biomarcadores , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação/genética
18.
Pediatr Surg Int ; 40(1): 57, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353772

RESUMO

PURPOSE: Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication. Long non-coding RNAs (lncRNAs) have utility as biomarkers for cancer diagnosis, prognosis, and disease monitoring. We hypothesize that expression of lncRNA, metastasis-associated lung adenocarcinoma transcript-1(MALAT1), is dysregulated and possibly trafficked within exosomes to influence the tissue microenvironment for metastasis and recurrence of WT. METHODS: We investigated the expression of MALAT1 in thirty WT samples by qPCR. Exosomes were isolated using a precipitated and affinity-binding-based kit, and characterized using TEM, NTA, and DLS. RESULTS: Mean number of exosomes was 9.01×108/mL in primary culture, 1.64×108/mL in urine, and 4.65×108/plasma:400µl. Average yield of total RNA was 1.28µg (primary-culture supernatant:1ml), 1.47µg (Urine:1ml), 1.65µg (Plasma:400 µL). We quantified MALAT1 in exosomes derived from these sources in patients of WT. Expression of MALAT1 was significantly downregulated (p=0.008) in WT samples. CONCLUSION: This is the first study that demonstrated the presence of lncRNA MALAT1 in various invasive and non-invasive samples of patients with WT(primary tissue culture, urine, and plasma samples).


Assuntos
Exossomos , Neoplasias Renais , RNA Longo não Codificante , Tumor de Wilms , Criança , Humanos , RNA Longo não Codificante/genética , Tumor de Wilms/genética , Neoplasias Renais/genética , Biópsia Líquida , Exossomos/genética , Microambiente Tumoral
20.
Anal Chem ; 96(9): 3698-3706, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38377543

RESUMO

Liquid biopsies have caused a significant revolution in cancer diagnosis, and the use of point of care (PoC) platforms has the potential to bring liquid biopsy-based cancer detection closer to patients. These platforms provide rapid and on-site analysis by reducing the time between sample collection and results output. The aim of this tutorial content is to provide readers an in-depth understanding regarding the choice of the ideal sensing platform suitable for specific cancer-related biomarkers.


Assuntos
Neoplasias , Humanos , Neoplasias/diagnóstico , Biópsia Líquida , Sistemas Automatizados de Assistência Junto ao Leito , Biomarcadores Tumorais/análise
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