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1.
Urol Clin North Am ; 50(1): 109-114, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36424075

RESUMO

Liquid biopsies such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have great potential to serve as prognostic and predictive biomarkers in urologic cancers. The possibility of using liquid biopsies for real-time noninvasive and dynamic monitoring of response to therapy has been an active area of investigation. In this brief review, we outline the evidence for the potential clinical utility of CTC and ctDNA analyses in prostate, urothelial, and renal cancers.


Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Neoplasias Urológicas , Masculino , Humanos , DNA Tumoral Circulante/genética , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/genética , Biópsia Líquida , Neoplasias Urológicas/genética
2.
Talanta ; 251: 123793, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952501

RESUMO

Circulating tumor cells (CTCs), as a type of tumor, have attracted wide attention because of their characteristics of shedding from the primary tumor and spreading to other tissues and organs through peripheral blood. The circulating tumor DNA (ctDNA), the DNA released by CTCs and other tumor cells into the peripheral blood, was considered as a promising detection substance for clinical application. By utilizing the biocompatibility of red blood cells to realize the attachment of tetrahedral DNA (TDN), as well as the specific target recognition ability of TDN to enable efficient recognition of targets, a biocompatible electrochemical biosensor for effective and rapid detection of ctDNA was developed using methylene blue (MB) as the signal probe. The current signal and the logarithm of ctDNA concentration were linearly correlated in the range from 1 fM to 100 pM with the detection limit of 0.66 fM. With high specificity, the TDN-based biosensor can detect ctDNA efficiently in the real biological environment such as serum, which provided a potential opportunity for the early clinical diagnosis.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Nanoestruturas , Células Neoplásicas Circulantes , DNA/química , Técnicas Eletroquímicas , Eritrócitos , Humanos , Limite de Detecção , Azul de Metileno , Nanoestruturas/química
3.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166583, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270476

RESUMO

DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias , Humanos , Metilação de DNA , Leucócitos Mononucleares , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias/genética
4.
Nat Commun ; 13(1): 7477, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463294

RESUMO

Acquired resistance to systemic treatments is inevitable in most cancers, but the genetic basis for this in many cancer types has remained elusive due to constraints in obtaining tissue specimens longitudinally. In the management of gastrointestinal cancers, molecular profiling is conventionally performed at a single time point, although serial evaluations may yield biological insights that inform treatment decisions. We characterize genetic changes in serial liquid biopsies which provide real-time snapshots of tumor genetics and heterogeneity in refractory non-colorectal gastrointestinal cancers, and determine the clinical utility of repeat circulating tumor DNA (ctDNA) testing. In a national cohort of 449 patients with pancreatic, biliary, esophagogastric, and hepatocellular cancers, resistance to conventional therapies is broadly associated with tumor evolution. Emergent ctDNA alterations only detectable at progression occurs in 63% of patients and are frequently associated with treatment actionability. Tumor mutation burden is dynamic in cancers undergoing treatment, but is not associated with time to progression. Objective tumor responses in a case series of patients receiving treatment matched to emergent alterations show that repeat liquid biopsies may have clinical benefit by expanding treatment options in advanced gastrointestinal cancers.


Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , DNA Tumoral Circulante/genética , Neoplasias Colorretais/genética , Biópsia Líquida , Neoplasias Hepáticas/genética , Administração Cutânea
5.
Cancer Discov ; 12(12): 2727-2729, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36458435

RESUMO

SUMMARY: Single biopsies fail to reflect intratumor heterogeneity and tumor evolution. In this issue of Cancer Discovery, Bosse and colleagues show an important role for circulating cell-free tumor DNA sequencing to detect the genomic evolution of neuroblastoma under ALK inhibitor therapy and identify novel (sub)clonal pathogenic variants involved in disease progression under conventional therapy. See related article by Bosse et al., p. 2800 (5).


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neuroblastoma , Humanos , DNA Tumoral Circulante/genética , Genômica , Neuroblastoma/genética , Acetaminofen , Aspirina , Ácidos Nucleicos Livres/genética
6.
Clin Epigenetics ; 14(1): 160, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457093

RESUMO

BACKGROUND: Recurrence represents a well-known poor prognostic factor for colorectal cancer (CRC) patients. This study aimed to establish an effective prognostic prediction model based on noninvasive circulating tumor DNA methylation markers for CRC patients receiving radical surgery. RESULTS: Two methylation markers (cg11186405 and cg17296166) were identified by Cox regression and receiver operating characteristics, which could classify CRC patients into high recurrence risk and low recurrence risk group. The 3-year disease-free survival was significantly different between CRC patients with low and high recurrence risk [Training set: hazard ratio (HR) 28.776, 95% confidence interval (CI) 3.594-230.400; P = 0.002; Validation set: HR 7.796, 95% CI 1.425-42.660, P = 0.018]. The nomogram based on the above two methylation markers and TNM stage was established which demonstrated robust prognostic prediction potential, as evidenced by the decision curve analysis result. CONCLUSIONS: A cell-free DNA methylation model consisting of two DNA methylation markers is a promising method for prognostic prediction in CRC patients.


Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Humanos , Intervalo Livre de Doença , DNA Tumoral Circulante/genética , Metilação de DNA , Intervalo Livre de Progressão , Biomarcadores , Neoplasias Colorretais/genética
7.
Oncogene ; 41(49): 5289-5297, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36329125

RESUMO

The use of conventional methods (immunohistochemistry, pentaplex PCR) for detecting microsatellite instability (MSI), a predictive biomarker of immunotherapy efficacy, is debated for cancers with low MSI prevalence, such as breast cancer (BC). We developed two multiplex drop-off droplet digital PCR (ddPCR) assays targeting four microsatellites, initially identified from public BC whole-genome sequencing dataset. Performances of the assays were investigated and 352 tumor DNA and 28 circulating cell-free DNA from BC patients, with unknown MSI status were blindly screened. Cross-validation of ddPCR MSI status with other MSI detection methods was performed. We then monitored circulating tumor DNA (ctDNA) dynamics before and during pembrolizumab immunotherapy in one patient with MSI-high (MSI-H) metastatic BC. The assays showed high analytical specificity and sensitivity (limit of detection = 0.16%). Among N = 380 samples, seven (1.8%) were found as MSI-H by ddPCR with six of them confirmed by next-generation sequencing (NGS). Specificity was 100% in N = 133 microsatellite stable BC submitted to NGS. In the patient with MSI-H metastatic BC, ctDNA monitoring revealed an early decrease of microsatellite mutant allelic frequencies during immunotherapy. These results demonstrated MSI detection by ddPCR, a non-invasive, fast and cost-effective approach, allowing for large pre-screening of BC patients who may benefit from immunotherapy.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Neoplasias Colorretais , Humanos , Feminino , Instabilidade de Microssatélites , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase , Neoplasias Colorretais/genética
8.
BMC Med ; 20(1): 458, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434648

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood. METHODS: Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility. RESULTS: In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001). CONCLUSIONS: The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.


Assuntos
Carcinoma Ductal Pancreático , DNA Tumoral Circulante , Neoplasias Pancreáticas , Humanos , DNA Tumoral Circulante/genética , Antígeno CA-19-9 , Metilação , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia
9.
Clin Transl Med ; 12(11): e1116, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36437506

RESUMO

BACKGROUND: The potential of circulating tumour DNA (ctDNA) as a reliable biomarker for relapse/metastasis early detection and prognosis in esophageal squamous cell carcinoma (ESCC) after radiotherapy/chemoradiotherapy (RT/CRT) initiation requires comprehensive investigation. METHODS: Treatment-naive locally advanced ESCC patients with available baseline plasma samples were prospectively enrolled from November 2018 to January 2020. RT/CRT was delivered with a simultaneous integrated boost of radiation dose. Serial plasma samples were collected at baseline (T0 ), week 4 of RT/CRT (T1 ), 1-3 (T2 ) and 3-6 months post-RT/CRT (T3 ). ctDNA was analysed using next-generation sequencing of 474 cancer-relevant genes. RESULTS: A total of 128 plasma samples from 40 eligible patients were analysed (median age: 64 [range: 40-78], 88% males, 95% stage III/IV), and the median follow-up time was 20.6 months (range: 12.2-33.3). During the post-RT/CRT surveillance including 36 patients, radiological progression was observed in 16 patients, and 69% (11/16) had detectable post-RT/CRT ctDNA prior to radiological progression, with a median lead time of 4.4 months compared with radiological imaging. ctDNA positivity at T1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30-10.01) or T2 (HR: 5.45, 95% CI: 1.72-17.26) indicated inferior progression-free survival (PFS). ctDNA clearance between T0 -T1 (HR: 0.31, 95% CI: 0.08-1.13) or T0 -T2 (HR: 0.11; 95% CI: 0.02-0.61) was associated with relatively favourable PFS. Similar results were obtained when focusing on patients without esophagectomy after RT/CRT. Notably, detectable ctDNA at T1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31-15.04). CONCLUSIONS: ctDNA was identified as a robust biomarker for early detection of disease progression and post-RT/CRT prognosis stratification in ESCC. Detectable ctDNA at week 4 of RT/CRT might indicate higher local recurrence risks, implying the potential clinical utility of ctDNA tests in guiding post-RT/CRT treatments for locoregional control in ESCC.


Assuntos
DNA Tumoral Circulante , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , DNA Tumoral Circulante/genética , Prognóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/radioterapia
11.
Nat Med ; 28(11): 2353-2363, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36357680

RESUMO

Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05; 95% confidence interval (CI), 1.74-2.42; P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63; 95% CI, 0.52-0.76; P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , DNA Tumoral Circulante/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Mutação , Sequenciamento de Nucleotídeos em Larga Escala
12.
Clin. transl. oncol. (Print) ; 24(11): 2155-2165, noviembre 2022. graf, tab
Artigo em Inglês | IBECS | ID: ibc-210143

RESUMO

Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).MethodsIn this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).ResultsBetween February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.ConclusionsThe BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation. (AU)


Assuntos
Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , DNA Tumoral Circulante/genética , Neoplasias do Colo/etiologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
13.
Sci Transl Med ; 14(670): eabo3958, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350985

RESUMO

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics, triggering studies to understand the molecular and cellular wiring of response and resistance. Our increased understanding of the underlying biology of response to ICI has enabled the investigation of tumor-intrinsic and -extrinsic features that may predict therapeutic outcomes. In parallel, liquid biopsy measurements of circulating tumor DNA (ctDNA) can be used to assess real-time molecular responses and guide clinical decisions during ICI. The combination of these approaches provides a deeper understanding of cancer biology, immunoediting, and evolution during ICI and promise to extend the utility of immunotherapies for patients with cancer.


Assuntos
DNA Tumoral Circulante , Neoplasias , Humanos , Imunoterapia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , DNA Tumoral Circulante/genética , Biomarcadores Tumorais
14.
Biosensors (Basel) ; 12(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36354498

RESUMO

An electrochemical-DNA (E-DNA) sensor was constructed by using DNA metallization to produce an electrochemical signal reporter in situ and hybridization chain reaction (HCR) as signal amplification strategy. The cyclic voltammetry (CV) technique was used to characterize the electrochemical solid-state Ag/AgCl process. Moreover, the enzyme cleavage technique was introduced to reduce background signals and further improve recognition accuracy. On the basis of these techniques, the as-prepared E-DNA sensor exhibited superior sensing performance for trace ctDNA analysis with a detection range of 0.5 fM to 10 pM and a detection limit of 7 aM. The proposed E-DNA sensor also displayed excellent selectivity, satisfied repeatability and stability, and had good recovery, all of which supports its potential applications for future clinical sample analysis.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Técnicas Biossensoriais/métodos , Limite de Detecção , Hibridização de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , DNA/química , Técnicas Eletroquímicas/métodos
15.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430675

RESUMO

Identifying novel circulating biomarkers predictive of response and informative about the mechanisms of resistance, is the new challenge for breast cancer (BC) management. The integration of omics information will gradually revolutionize the clinical approach. Liquid biopsy is being incorporated into the diagnostic and decision-making process for the treatment of BC, in particular with the analysis of circulating tumor DNA, although with some relevant limitations, including costs. Circulating cell-free DNA (cfDNA) fragmentomics and its integrity index may become a cheaper, noninvasive biomarker that could provide significant additional information for monitoring response to systemic treatments in BC. The purpose of our review is to focus on the available research on cfDNA integrity and its features as a biomarker of diagnosis, prognosis and response to treatments in BC, highlighting new perspectives and critical issues for future applications.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Humanos , Feminino , Ácidos Nucleicos Livres/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Biomarcadores Tumorais/genética , Biópsia Líquida
18.
BMC Med ; 20(1): 398, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372873

RESUMO

BACKGROUND: Due to the blood-brain barrier, plasma is not an ideal source to evaluate the genetic characteristics of central nervous system tumors. Thus, cerebrospinal fluid (CSF) is becoming an alternative biopsy type to evaluate the genetic landscape of intracranial tumors. We aimed to explore the genetic profiles of CSF-derived circulating tumor DNA (ctDNA) to predict intracranial tumor responses and monitor mutational evolution during the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases. METHODS: We conducted a prospective study of 92 newly diagnosed NSCLC patients with brain metastases. Paired CSF and plasma samples were collected at baseline, 8 weeks after treatment initiation, and disease progression. All samples underwent next-generation sequencing of 425 cancer-related genes. RESULTS: At baseline, the positive detection rates of ctDNA in CSF, plasma, and extracranial tumors were 63.7% (58/91), 91.1% (82/90), and 100% (58/58), respectively. A high level of genetic heterogeneity was observed between paired CSF and plasma, while concordance in driver mutations was also observed. A higher number of unique copy number variations was detected in CSF-ctDNA than in plasma. ctDNA positivity of CSF samples at baseline was associated with poor outcomes (HR=2.565, P=0.003). Moreover, patients with ≥ 50% reductions in the concentrations of CSF ctDNA after 8 weeks of treatment had significantly longer intracranial progression-free survivals (PFS) than patients with < 50% reductions in CSF ctDNA concentrations (13.27 months vs 6.13 months, HR=0.308, P=0.017). A ≥ 50% reduction in CSF ctDNA concentrations had better concordance with radiographic intracranial tumor responses than plasma. A ≥ 50% reduction in plasma ctDNA concentrations was also associated with longer extracranial PFS (11.57 months vs 6.20 months, HR=0.406, P=0.033). Based on clonal evolution analyses, the accumulation of subclonal mutations in CSF ctDNA was observed after 8 weeks of treatment. The clonal mutations that remained in more than 80% in CSF after 8 weeks also predicted shorter intracranial PFS (HR=3.785, P=0.039). CONCLUSIONS: CSF ctDNA exhibited unique genetic profiles of brain metastases, and dynamic changes in CSF ctDNA could better predict intracranial tumor responses and track clonal evolution during treatment in NSCLC patients with brain metastases. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03257735.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Variações do Número de Cópias de DNA , Perfil Genético , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Estudos Prospectivos
19.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361758

RESUMO

Cancer is a predominant cause of mortality all over the world. Lung, prostate, and colorectal cancer are the more frequent in men while breast and colorectal have a high incidence in women. Major progress aside, some cancers are still frequent and one major issue is improvements in detection methods. Imaging techniques have a major role, but inflammatory, tumoral markers and calculated scores may contribute to the assessment of prognosis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and carcinoembryonic antigen cell adhesion molecule (CEACAM) have been used for decades and do not have a clear use for diagnosis or prognosis yet. The CEACAM family includes 12 human members, and some of them have a cluster differentiation (CD). CD66 may be an interesting indicator of disease severity. Beside interleukin-6 (IL-6), the high level of which is observed in patients with a high mortality rate, other cytokines IL-17A, IL-22, and transforming growth factor -ß (TGF-ß) are expressed at the tumor level. The detection of circulating tumor cells has been improved but is still of undetermined value. Circulating tumor DNA (ctDNA) was recently studied in CRC stage II patients and may be helpful for chemotherapy management.


Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Células Neoplásicas Circulantes , Masculino , Humanos , Feminino , Neoplasias Colorretais/patologia , Antígeno Carcinoembrionário , Biomarcadores Tumorais/genética , Células Neoplásicas Circulantes/metabolismo , Proteína C-Reativa
20.
JCO Precis Oncol ; 6: e2200244, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36356286

RESUMO

PURPOSE: Prognostic tools to estimate the risk of relapse for patients with liver-limited metastatic colorectal cancer (LL-mCRC) undergoing resection with curative intent are needed. Circulating tumor DNA (ctDNA) as a surrogate of postsurgical minimal residual disease is a promising marker in localized CRC. We explored the role of postoperative ctDNA as a marker of minimal residual disease in patients with radically resected LL-mCRC. MATERIALS AND METHODS: Seventy-six patients with LL-mCRC were retrospectively included. DNA from tumor tissue was sequenced, and one somatic mutation was then assessed by digital droplet polymerase chain reaction in plasma samples collected after surgery to identify the persistence of ctDNA. Relapse-free survival and postresection overall survival were compared between patients with positive vs negative postoperative ctDNA. RESULTS: ctDNA was found in 39 (51%) of 76 patients with LL-mCRC. At a median follow-up of 77 months, 33 of 39 ctDNA-positive patients and 20 of 37 ctDNA-negative patients experienced disease relapse (P = .008). ctDNA-positive patients reported significantly shorter RFS than ctDNA-negative ones (median RFS 12.7 v 27.4 months hazard ratio, 2.09, P = .008). In the multivariable model including other prognostic covariates, this association was still significant (P = .046) and a trend toward shorter overall survival among ctDNA-positive patients was reported (hazard ratio, 1.65, P = .183). CONCLUSION: The detection of postsurgical ctDNA is an independent negative prognostic marker and identifies patients at high risk of relapse after liver metastases resection.


Assuntos
DNA Tumoral Circulante , Neoplasias do Colo , Neoplasias Hepáticas , Humanos , DNA Tumoral Circulante/genética , Neoplasia Residual , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/diagnóstico , Estudos Prospectivos , Neoplasias Hepáticas/diagnóstico , Neoplasias do Colo/patologia
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