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1.
Inorg Chem ; 61(22): 8455-8466, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35608075

RESUMO

Hydrogen peroxide is produced upon radiolysis of water and has been shown to be the main oxidant driving oxidative dissolution of UO2-based nuclear fuel under geological repository conditions. While the overall mechanism and speciation are well known for granitic groundwaters, considerably less is known for saline waters of relevance in rock salt or during emergency cooling of reactors using seawater. In this work, the ternary uranyl-peroxo-chloro and uranyl-peroxo-bromo complexes were identified using IR, Raman, and nuclear magnetic resonance (NMR) spectroscopy. Based on Raman spectra, the estimated stability constants for the identified uranyl-peroxo-chloro ((UO2)(O2)(Cl)(H2O)2-) and uranyl-peroxo-bromo ((UO2)(O2)(Br)(H2O)2-) complexes are 0.17 and 0.04, respectively, at ionic strength ≈5 mol/L. It was found that the uranyl-peroxo-chloro complex is more stable than the uranyl-peroxo-bromo complex, which transforms into studtite at high uranyl and H2O2 concentrations. Studtite is also found to be dissolved at a high ionic strength, implying that this may not be a stable solid phase under very saline conditions. The uranyl-peroxo-bromo complex was shown to facilitate H2O2 decomposition via a mechanism involving reactive intermediates.


Assuntos
Compostos de Urânio , Peróxido de Hidrogênio/química , Espectroscopia de Ressonância Magnética , Oxidantes/química , Oxirredução , Compostos de Urânio/química
2.
ACS Omega ; 7(18): 15929-15935, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35571836

RESUMO

The interfacial radiation chemistry of UO2 is of key importance in the development of models to predict the corrosion rate of spent nuclear fuel in contact with groundwater. Here, the oxidative dissolution of UO2 induced by radiolytically produced H2O2 is of particular importance. The difficulty of fitting experimental data to simple first-order kinetics suggests that additional factors need to be considered when describing the surface reaction between H2O2 and UO2. It has been known for some time that UO2 2+ forms stable uranyl peroxo-carbonato complexes in water containing H2O2 and HCO3 -/CO3 2-, yet this concept has largely been overlooked in studies where the oxidative dissolution of UO2 is considered. In this work, we show that uranyl peroxo-carbonato complexes display little to no reactivity toward the solid UO2 surface in 10 mM bicarbonate solution (pH 8-10). The rate of peroxide consumption and UO2 2+ dissolution will thus depend on the UO2 2+ concentration and becomes limited by the free H2O2 fraction. The rate of peroxide consumption and the subsequent UO2 2+ dissolution can be accurately predicted based on the first-order kinetics with respect to free H2O2, taking the initial H2O2 surface coverage into account.

3.
Angew Chem Int Ed Engl ; 61(6): e202112204, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34860450

RESUMO

The role of intermediate phases in CeO2 mesocrystal formation from aqueous CeIII solutions subjected to γ-radiation was studied. Radiolytically formed hydroxyl radicals convert soluble CeIII into less soluble CeIV . Transmission electron microscopy (TEM) and X-ray diffraction studies of samples from different stages of the process allowed the identification of several stages in CeO2 mesocrystal evolution following the oxidation to CeIV : (1) formation of hydrated CeIV hydroxides, serving as intermediates in the liquid-to-solid phase transformation; (2) CeO2 primary particle growth inside the intermediate phase; (3) alignment of the primary particles into "pre-mesocrystals" and subsequently to mesocrystals, guided by confinement of the amorphous intermediate phase and accompanied by the formation of "mineral bridges". Further alignment of the obtained mesocrystals into supracrystals occurs upon slow drying, making it possible to form complex hierarchical architectures.

4.
Nat Cancer ; 2(11): 1224-1242, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34870237

RESUMO

Despite major advancements in lung cancer treatment, long-term survival is still rare, and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune evasion mechanisms. Here we performed in-depth mass spectrometry (MS)-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition MS-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteogenômica , Carcinoma Pulmonar de Células não Pequenas/genética , Fibrinogênio/uso terapêutico , Genômica/métodos , Humanos , Evasão da Resposta Imune/genética , Neoplasias Pulmonares/genética
5.
Dalton Trans ; 50(45): 16849, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34766613

RESUMO

Correction for 'Mixed H2O/H2 plasma-induced redox reactions of thin uranium oxide films under UHV conditions' by Ghada El Jamal et al., Dalton Trans., 2021, DOI: 10.1039/d1dt01020d.

6.
ACS Omega ; 6(37): 24289-24295, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34568706

RESUMO

Uranium carbide (UC) is a candidate fuel material for future Generation IV nuclear reactors. As part of a general safety assessment, it is important to understand how fuel materials behave in aqueous systems in the event of accidents or upon complete barrier failure in a geological repository for spent nuclear fuel. As irradiated nuclear fuel is radioactive, it is important to consider radiolysis of water as a process where strongly oxidizing species can be produced. These species may display high reactivity toward the fuel itself and thereby influence its integrity. The most important radiolytic oxidant under repository conditions has been shown to be H2O2. In this work, we have studied the dissolution of uranium upon exposure of UC powder to aqueous solutions containing HCO3 - and H2O2, separately and in combination. The experiments show that UC dissolves quite readily in aqueous solution containing 10 mM HCO3 - and that the presence of H2O2 increases the dissolution further. UC also dissolves in pure water after the addition of H2O2, but more slowly than in solutions containing both HCO3 - and H2O2. The experimental results are discussed in view of possible mechanisms.

7.
Dalton Trans ; 50(36): 12583-12591, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34286754

RESUMO

X-ray photoelectron spectroscopy (XPS) has been used to study the effect of mixed H2O/H2 gas plasma on the surfaces of UO2, U2O5 and UO3 thin films at 400 °C. The experiments were performed in situ under ultra-high vacuum conditions. Deconvolution of the U4f7/2 peaks into U(IV), U(V) and U(VI) components revealed the surface composition of the films after 10 min plasma exposure as a function of H2 concentration in the feed gas of the plasma. Some selected films (unexposed and exposed) were also analysed using grazing-incidence X-ray diffraction (GIXRD). The XPS results show that U(V) is formed as a major product upon 10 minutes exposure of UO3 by a mixed H2O/H2 plasma in a fairly wide H2 concentration range. When starting with U(V) (U2O5), rather high H2 concentrations are needed to reduce U(V) to U(IV) in 10 minutes. In the plasma induced oxidation of UO2, U(V) is never observed as a major product after 10 minutes and it would seem that once U(V) is formed in the oxidation of UO2 it is rapidly oxidized further to U(VI). The grazing incidence X-ray diffraction analysis shows that there is a considerable impact of the plasma and heating conditions on the crystal structure of the films in line with the change of the oxidation state. This structural difference is proposed to be the main kinetic barrier for plasma induced transfer between U(IV) and U(V) in both directions.

8.
Dalton Trans ; 50(14): 4796-4804, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33877177

RESUMO

Thin UO2 films exposed to water plasma under UHV conditions have been shown to be interesting models for radiation induced oxidative dissolution of spent nuclear fuel. This is partly attributed to the fact that several of the reactive oxidizing and reducing species in a water plasma are also identified as products of radiolysis of water. Exposure of UO2 films to water plasma has previously been shown to lead to oxidation from U(iv) to U(v) and (vi). In this work we have studied the dynamics of water plasma induced redox changes in UO2 films by monitoring UO2 films using X-Ray photoelectron Photoemission (XPS) and Ultra-Violet Photoemission (UPS) spectroscopy as a function of exposure time. The surface composition in terms of oxidation states obtained from U4f7/2 peak deconvolution could be retraced along the exposure time, and compared to the valence band. The spectral analysis showed that U(iv) is initially oxidized to U(v) which is subsequently oxidized to U(vi). For extended exposure times it was shown that U(vi) is slowly reduced back to U(v). UPS data show that, unlike the U(v) formed on the surface upon oxidation of U(iv), the U(v) formed upon reduction of U(vi) is localized in the bulk of the film. It also displays a different reactivity than the initially formed U(v). The experiments can be reproduced using a simple kinetic model describing the redox processes involved.

9.
Dalton Trans ; 50(19): 6568-6577, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33890958

RESUMO

Two uranyl peroxides meta-studtite and studtite exist in nature and can form as alteration phases on the surface of spent nuclear fuel upon water intrusion in a geological repository. Meta-studtite and studtite have very low solubility and could therefore reduce the reactivity of spent nuclear fuel toward radiolytic oxidants. This would inhibit the dissolution of the fuel matrix and thereby also the spreading of radionuclides. It is therefore important to investigate the stability of meta-studtite and studtite under conditions that may influence their stability. In the present work, we have studied the dissolution kinetics of meta-studtite in aqueous solution containing 10 mM HCO3-. In addition, the influence of the added H2O2 and the impact of γ-irradiation on the dissolution kinetics of meta-studtite were studied. The results are compared to previously published data for studtite studied under the same conditions. 13C NMR experiments were performed to identify the species present in aqueous solution (i.e., carbonate containing complexes). The speciation studies are compared to calculations based on published equilibrium constants. In addition to the dissolution experiments, experiments focussing on the stability of H2O2 in aqueous solutions containing UO22+ and HCO3- were conducted. The rationale for this is that H2O2 was consumed relatively fast in some of the dissolution experiments.

10.
Methods Mol Biol ; 2279: 91-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33683688

RESUMO

In non-small cell lung cancer (NSCLC), mutation detection and fusion gene status are treatment predictive and, hence, key factors in clinical management. Lately, alternate splicing variants of MET have gained focus as NSCLC tumors harboring a MET exon 14 skipping event have proven sensitive toward targeted therapy. Reliable methods for detection of genetic alterations in NSCLC have proven to be of increased importance. This chapter provides with hands-on experience of the NanoString gene expression platform for detection of genetic alterations in NSCLC.


Assuntos
Processamento Alternativo , Carcinoma Pulmonar de Células não Pequenas , Éxons , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-met , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-met/biossíntese , Proteínas Proto-Oncogênicas c-met/genética
11.
Int J Cancer ; 148(1): 238-251, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32745259

RESUMO

Disease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression-based AC subtypes such as the Cancer Genome Atlas Network (TCGA) terminal-respiratory unit (TRU), proximal-inflammatory (PI) and proximal-proliferative (PP) subtypes have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype assignment and risk stratification that could function in a clinical setting. Two-class (TRU/nonTRU=SSP2) and three-class (TRU/PP/PI=SSP3) SSPs using the AIMS algorithm were trained in 1655 ACs (n = 9659 genes) from public repositories vs TCGA centroid subtypes. Validation and survival analysis were performed in 977 patients using overall survival (OS) and distant metastasis-free survival (DMFS) as endpoints. In the validation cohort, SSP2 and SSP3 showed accuracies of 0.85 and 0.81, respectively. SSPs captured relevant biology previously associated with the TCGA subtypes and were associated with prognosis. In survival analysis, OS and DMFS for cases discordantly classified between TCGA and SSP2 favored the SSP2 classification. In resected Stage I patients, SSP2 identified TRU-cases with better OS (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.18-0.49) and DMFS (TRU HR = 0.52; 95% CI = 0.33-0.83) independent of age, Stage IA/IB and gender. SSP2 was transformed into a NanoString nCounter assay and tested in 44 Stage I patients using RNA from formalin-fixed tissue, providing prognostic stratification (relapse-free interval, HR = 3.2; 95% CI = 1.2-8.8). In conclusion, gene expression-based SSPs can provide molecular subtype and independent prognostic information in early-stage lung ACs. SSPs may overcome critical limitations in the applicability of gene signatures in lung cancer.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/diagnóstico , Pulmão/patologia , Recidiva Local de Neoplasia/epidemiologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/cirurgia , Algoritmos , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Modelos Genéticos , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Fatores de Risco
12.
Dalton Trans ; 50(2): 729-738, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33346296

RESUMO

Thin films of UO2, U2O5, and UO3 were prepared in situ and exposed to reactive gas plasmas of O2, H2 and H2O vapour produced with an ECR plasma source (electron cyclotron resonance) under UHV conditions. The plasma constituents were analysed using a residual gas analyser mass spectrometer. For comparison, the thin films were also exposed to the plasma precursor gases under comparable conditions. Surface analysis was conducted using X-Ray and ultraviolet photoelectron spectroscopy before and after exposure, by measuring the U 4f, O 1s core levels and the valence band region. The evolution of the peaks was monitored as a function of temperature and time of exposure. After interacting with water plasma at 400 °C, the surface of UO2 was oxidized to a higher oxidation state compared to when starting with U2O5 while the UO3 film displayed weak surface reduction. When exposed to water plasma at ambient temperature, the outermost surface layer is composed of hexavalent uranium in all three cases.

13.
Chemosphere ; 263: 127686, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33296996

RESUMO

Solubilisation of Ni(II) and Eu(III) by complexation with a polyaryl ether based superplasticizer (PAE SP) in alkaline solutions was studied. The solubilisation was investigated in two types of artificial cement pore waters simulating different stages of cement degradation at a pH of 12.4 and 13.3, respectively. The solubility of Ni(II) and Eu(III) increased as the concentration of superplasticizer was increased from 0.04 to 0.4 wt%. When the concentration of SP was increased from 0.4 to 4%, the solubility of Eu(III) and Ni(II) increased in the pore water with a pH of 12.4, while the concentrations decreased in the pore water with a pH of 13.3. This is explained by a more rapid degradation of the superplasticizer at higher pH leading to a release of phosphate groups and thereby precipitation of Eu(III) and Ni(II) as phosphates. Based on results of the solubilisation of Ni(II) and Eu(III) by model compounds (anisole and PEG 400) and 31P NMR spectroscopy it was confirmed that the complexation of the studied metals with the PAE polymer occurs via the phosphate group of the superplasticizer.


Assuntos
Éter , Metais , Concentração de Íons de Hidrogênio , Fosfatos , Solubilidade
14.
Cancer Med ; 9(15): 5609-5619, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32491279

RESUMO

AIMS: High expression of the RNA-binding motif protein 3 (RBM3) correlates with improved prognosis in several major types of cancer. The aim of the present study was to examine the prognostic value of RBM3 protein and mRNA expression in non-small cell lung cancer (NSCLC). METHODS AND RESULTS: Immunohistochemical expression of RBM3 was evaluated in surgically treated NSCLC from two independent patient populations (n = 213 and n = 306). Staining patterns were correlated with clinicopathological parameters, overall survival (OS), and recurrence-free interval (RFI). Cases with high nuclear RBM3 protein expression had a prolonged 5-year OS in both cohorts when analyzing adenocarcinomas separately (P = .02 and P = .01). RBM3 remained an independent prognostic factor for OS in multivariable analysis of cohort I (HR 0.44, 95% CI 0.21-0.90) and for RFI in cohort II (HR 0.38, 95% CI 0.22-0.74). In squamous cell carcinoma, there was instead an insignificant association to poor prognosis. Also, the expression levels of RBM3 mRNA were investigated in 2087 lung adenocarcinomas and 899 squamous cell carcinomas assembled from 13 and 8 public gene expression microarray datasets, respectively. The RBM3 mRNA levels were not clearly associated with patient outcome in either adenocarcinomas or squamous cell carcinomas. CONCLUSIONS: The results from this study support that high protein expression of RBM3 is linked to improved outcome in lung adenocarcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética
15.
Dalton Trans ; 49(6): 1907-1914, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31970362

RESUMO

This study aims to reveal possible involvements of organic acids in the oxidative dissolution of UO2. Using phthalic acid as a model compound, we have measured adsorption on UO2 and investigated effects on the reaction between H2O2 and UO2 and on oxidative dissolution induced by γ-irradiation. Significant adsorption of phthalic acid was observed even at neutral pH. However, the reaction between H2O2 and UO2 in phthalic acid solution induced oxidative dissolution of U(vi) similar to in aqueous bicarbonate solution. Moreover, degradation products of phthalic acid were not detected after the reaction of H2O2. These results indicate that even though phthalic acid adsorbs on the UO2 surface, it is not involved in the interfacial reaction of H2O2. In contrast, the dissolution of U by irradiation was inhibited in aqueous phthalic acid solution, whereas H2O2 generated by radiolysis was consumed by UO2. Based on these contrasting results, possible roles of radical species generated by water radiolysis were discussed.

16.
Dalton Trans ; 49(4): 1241-1248, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31904047

RESUMO

To assess the long-term leaching behaviour of UO2, the main constituent of spent nuclear fuel, the oxidative dissolution of UO2 pellets was studied at high H2O2 exposures ranging from 0.33 mol m-2 to 1.36 mol m-2. The experiments were performed in aqueous media containing 10 mM HCO3- where the pellets were exposed to H2O2 three consecutive times. The results indicate that the dissolution yield (amount of dissolved uranium per consumed H2O2) at high H2O2 exposures is significantly lower compared to previous studies of both pellets and powders and decreases for each H2O2 addition for a given pellet. This implies a change in redox reactivity, which is attributed to irreversible alteration of the pellet surface. Surface characterization after the exposure to H2O2, by SEM, XRD and Raman spectroscopy shows, that the surface of all pellets is significantly oxidized.

17.
Biomolecules ; 11(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396401

RESUMO

Bio-hybrid hydrogels consist of a water-swollen hydrophilic polymer network encapsulating or conjugating single biomolecules, or larger and more complex biological constructs like whole cells. By modulating at least one dimension of the hydrogel system at the micro- or nanoscale, the activity of the biological component can be extremely upgraded with clear advantages for the development of therapeutic or diagnostic micro- and nano-devices. Gamma or e-beam irradiation of polymers allow a good control of the chemistry at the micro-/nanoscale with minimal recourse to toxic reactants and solvents. Another potential advantage is to obtain simultaneous sterilization when the absorbed doses are within the sterilization dose range. This short review will highlight opportunities and challenges of the radiation technologies to produce bio-hybrid nanogels as delivery devices of therapeutic biomolecules to the target cells, tissues, and organs, and to create hydrogel patterns at the nano-length and micro-length scales on surfaces.


Assuntos
Hidrogéis/química , Nanopartículas/química , Engenharia Tecidual , Hidrogéis/efeitos da radiação , Nanopartículas/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Radiação Ionizante
18.
JTO Clin Res Rep ; 1(1): 100013, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34589915

RESUMO

OBJECTIVES: Mutation analysis by massive parallel sequencing (MPS) is routinely performed in the clinical management of lung cancer in Sweden. We describe the clinical and mutational profiles of lung cancer patients subjected to the first 1.5 years of treatment predictive MPS testing in an autonomous regional health care region. METHODS: Tumors from all patients with lung cancer who had an MPS test from January 2015 to June 2016 in the Skåne health care region in Sweden (1.3 million citizens) were included. Six hundred eleven tumors from 599 patients were profiled using targeted sequencing with a 26-gene exon-focused panel. Data on disease patterns and characteristics of the patients subjected to testing were assembled, and correlations between mutational profiles and clinical features were analyzed. RESULTS: MPS with the 26-gene panel revealed alterations in 92% of the 611 lung tumors, with the most frequent mutations detected in the nontargetable genes TP53 (62%) and KRAS (37%). Neither KRAS nor TP53 mutations were associated with disease pattern, chemotherapy response, progression-free survival, or overall survival in advanced-stage disease treated with platinum-based doublet chemotherapy as a first-line treatment. Among targetable genes, EGFR driver mutations were detected in 10% of the tumors, and BRAF p.V600 variants in 2.3%. For the 71 never smokers (12%), targetable alterations (EGFR mutations, BRAF p.V600, MET exon 14 skipping, or ALK/ROS1 rearrangement) were detected in 59% of the tumors. CONCLUSION: Although the increasing importance of MPS as a predictor of response to targeted therapies is indisputable, its role in prognostics or as a predictor of clinical course in nontargetable advanced stage lung cancer requires further investigation.

20.
Acta Oncol ; 58(8): 1079-1086, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230502

RESUMO

Background: Lung cancer patients have a risk of recurrence even after curatively intended surgery. Cell-free circulating tumor DNA (ctDNA) and circulating tumor marker measurements are easily accessible through peripheral blood and could potentially identify patients with worse prognosis. The aim of this study was to examine ctDNA in pre-operative plasma and the role of tumor markers in pre-operative serum for their predictive potential on risk of tumor recurrence. Methods: Mutation analysis by 26-gene targeted sequencing was performed on 157 lung adenocarcinomas (ACs) from patients surgically treated at the Lund University Hospital 2005-2014. Of these, 58 tumors from patients in stages I-IIIA (34 stage I, 14 stage II and 10 stage III) with mutation(s) in EGFR, BRAF or KRAS were included. ctDNA from corresponding plasma (median 1.5 ml, range 1-1.6) was analyzed for one tumor-specific mutation in either of these three oncogenes using ultrasensitive IBSAFE droplet digital PCR (ddPCR). The tumor markers cancer antigen 125 (CA 125) and carbohydrate antigen 19-9 (CA 19-9) were analyzed in corresponding serum with electrochemiluminiscence immunoassay. Results: 6/7 patients with ctDNA and 19/51 without detected ctDNA were diagnosed with recurrence (log-rank test p = .001). 8/10 patients with positive serum tumor markers and 17/47 without tumor markers were diagnosed with recurrence (log-rank test, p = .0002). Fifteen patients had positive ctDNA and/or tumor markers, 12 of these had recurrence (log-rank test, p < .0001). Conclusion: A combination of tumor markers and ctDNA single mutation detection in low-volume pre-operative blood samples is a promising prognostic test. Prediction of recurrent disease in surgically treated early stage lung cancer can likely be further improved by using larger volumes of blood.


Assuntos
Adenocarcinoma de Pulmão/sangue , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/sangue , Recidiva Local de Neoplasia/diagnóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , DNA Tumoral Circulante/isolamento & purificação , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Pneumonectomia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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