Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
2.
Sci Rep ; 14(1): 1778, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245572

RESUMO

Protein kinase C substrate 80K-H (PRKCSH) plays a crucial role in the protein N-terminal glycosylation process, with emerging evidence implicating its involvement in tumorigenesis. To comprehensively assess PRKCSH's significance across cancers, we conducted a pan-cancer analysis using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We assessed aberrant PRKCSH mRNA and protein expression, examined its prognostic implications, and identified correlations with clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immunity across cancer types. We explored PRKCSH gene alterations, DNA methylation, and their impact on patient prognosis. Gene Set Enrichment Analysis (GSEA) and single-cell analysis revealed potential biological roles. Additionally, we investigated drug susceptibility and conducted Connectivity Map (Cmap) analysis. Key findings revealed that PRKCSH exhibited overexpression in most tumors, with a significant association with poor overall survival (OS) in six cancer types. Notably, PRKCSH expression demonstrated variations across disease stages, primarily increasing in advanced stages among eleven tumor types. Moreover, PRKCSH exhibited significant correlations with TMB in five cancer categories, MSI in eight, and displayed associations with immune cell populations in pan-cancer analysis. Genetic variations in PRKCSH were identified across 26 tumor types, suggesting favorable disease-free survival. Furthermore, PRKCSH methylation displayed a significant negative correlation with its expression in 27 tumor types, with a marked decrease compared to normal tissues in ten tumors. Cmap predicted 24 potential therapeutic small molecules in over four cancer types. This study highlights that PRKCSH, as a potential oncogene, may be a promising prognostic marker and therapeutic target of immunotherapy for a range of malignancies.


Assuntos
Neoplasias , Humanos , Prognóstico , Neoplasias/genética , Oncogenes , Carcinogênese , Instabilidade de Microssatélites , Biomarcadores , Proteínas de Ligação ao Cálcio , Glucosidases
3.
Transl Neurodegener ; 12(1): 53, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012808

RESUMO

BACKGROUND: Synaptic degeneration occurs in the early stage of Alzheimer's disease (AD) before devastating symptoms, strongly correlated with cognitive decline. Circular RNAs (circRNAs) are abundantly enriched in neural tissues, and aberrant expression of circRNAs precedes AD symptoms, significantly correlated with clinical dementia severity. However, the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly understood. METHODS: Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 mice. RNA antisense purification and mass spectrometry were utilized to unveil interactions between circRIMS2 and methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3). The roles of circRIMS2/miR-3968 in synaptic targeting of UBE2K-mediated ubiquitination of GluN2B subunit of NMDA receptor were evaluated via numerous lentiviruses followed by morphological staining, co-immunoprecipitation and behavioral testing. Further, a membrane-permeable peptide was used to block the ubiquitination of K1082 on GluN2B in AD mice. RESULTS: circRIMS2 was significantly upregulated in 4-month-old APP/PS1 mice, which was mediated by METTL3-dependent N6-methyladenosine (m6A) modification. Overexpression of circRIMS2 led to synaptic and memory impairments in 4-month-old C57BL/6 mice. MiR-3968/UBE2K was validated as the downstream of circRIMS2. Elevated UBE2K induced synaptic dysfunction of AD through ubiquitinating K1082 on GluN2B. Silencing METTL3 or blocking the ubiquitination of K1082 on GluN2B with a short membrane-permeable peptide remarkably rescued synaptic dysfunction in AD mice. CONCLUSIONS: In conclusion, our study demonstrated that m6A-modified circRIMS2 mediates the synaptic and memory impairments in AD by activating the UBE2K-dependent ubiquitination and degradation of GluN2B via sponging miR-3968, providing novel therapeutic strategies for AD.


Assuntos
Doença de Alzheimer , MicroRNAs , RNA Circular , Receptores de N-Metil-D-Aspartato , Animais , Camundongos , Adenosina , Doença de Alzheimer/metabolismo , Transtornos da Memória/genética , Metiltransferases , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Peptídeos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , RNA Circular/genética
4.
J Cancer Res Clin Oncol ; 149(19): 17285-17296, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37815661

RESUMO

BACKGROUND: Bile acids (BA) are important metabolites and serve as signaling molecules, which are involve in multiple cancer-related signaling pathways. METHODS: A validated LC-MS/MS approach was applied in a case-control study with 220 non-small cell lung cancer (NSCLC) patients and 244 matched healthy controls. The concentrations of seven common types of BAs in serum were determined and compared. Subgroup analyses based on demographic factor, lifestyle, pathologic types and tumor stage were conducted. Machine learning analysis was performed for NSCLC classification. RESULTS: Serum levels of primary BAs, including cholic acid (CA), taurocholic acid (TCA) and glycocholic acid (GCA), were upregulated, while lithocholic acid (LCA), a type of secondary BA, was downregulated in NSCLC patients compared with healthy controls in overall analysis. Higher level of chenodeoxycholic acid (CDCA) and lower level of ursodeoxycholic acid (UDCA) were observed in female, elder, overweight patients, as well as patients without alcohol use in comparison with controls. CDCA and CA levels were higher only in lung adenocarcinoma (LUAD), and UDCA and DCA levels were lower only in squamous cell carcinoma (LUSC), while the concentrations of TCA, GCA, and LCA were altered prevalently in LUAD and LUSC patients. For discrimination of NSCLC from healthy people, the area under the receiver operating characteristics (ROC) curve of the models through support vector machine (SVM) approach was 0.91 (95% CI 0.88-0.94) in the training set and 0.84 (95% CI 0.78-0.91) in the validation set, respectively. CONCLUSIONS: Serum BAs were altered in NSCLC patients compared with controls, among which primary BAs were elevated and secondary BAs were decreased. Moreover, distinct patterns of BA alterations were revealed between LUAD patients and LUSC patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Casos e Controles , Cromatografia Líquida , Neoplasias Pulmonares/tratamento farmacológico , Espectrometria de Massas em Tandem , Ácidos e Sais Biliares
6.
Proteomics ; 23(20): e2300140, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37474491

RESUMO

Aberrant serum N-glycan profiles have been observed in multiple cancers including non-small-cell lung cancer (NSCLC), yet the potential of N-glycans in the early diagnosis of NSCLC remains to be determined. In this study, serum N-glycan profiles of 275 NSCLC patients and 309 healthy controls were characterized by MALDI-TOF-MS. The levels of serum N-glycans and N-glycosylation patterns were compared between NSCLC and control groups. In addition, a panel of N-glycan biomarkers for NSCLC diagnosis was established and validated using machine learning algorithms. As a result, a total of 54 N-glycan structures were identified in human serum. Compared with healthy controls, 29 serum N-glycans were increased or decreased in NSCLC patients. N-glycan abundance in different histological types or clinical stages of NSCLC presented differentiated changes. Furthermore, an optimal biomarker panel of eight N-glycans was constructed based on logistic regression, with an AUC of 0.86 in the validation set. Notably, this model also showed a desirable capacity in distinguishing early-stage patients from healthy controls (AUC = 0.88). In conclusion, our work highlights the abnormal N-glycan profiles in NSCLC and provides supports potential application of N-glycan biomarker panel in clinical NSCLC detection.

7.
Environ Toxicol Pharmacol ; 101: 104173, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37302441

RESUMO

Bisphenol A (BPA) can be metabolized by metabolic enzymes and may induce abnormal lipid metabolism. We hypothesized that BPA exposure and its interaction with metabolism-related genes might be associated with serum lipid profiles. We performed a two-stage study among 955 middle-aged and elderly participants in Wuhan, China. Urinary BPA level was estimated without (BPA, µg/L) or with (BPA/Cr, µg/g) adjustments for urinary creatinine and ln-transformed values (ln-BPA or ln-BPA/Cr) were used to normalize the asymmetrical distributions. A total of 412 metabolism-related gene variants were selected and used for gene-BPA interaction analysis. Multiple linear regression was used to analyze the interactions between BPA exposure and metabolism-related genes on serum lipid profiles. In the discovery stage, both ln-BPA and ln-BPA/Cr was associated with decreased high-density lipoprotein cholesterol (HDL-C). Gene-urinary BPA interaction for IGFBP7 rs9992658 was observed to associate with HDL-C levels in both discovery and validation stages, with Pinteraction equal to 9.87 × 10-4 (ln-BPA) and 1.22 × 10-3 (ln-BPA/Cr) in combined analyses. In addition, the inverse association of urinary BPA with HDL-C levels was only observed among individuals carrying rs9992658 AA genotype, but not in individuals carrying rs9992658 AC or CC genotypes. The interaction between BPA exposure and metabolism-related gene IGFBP7 (rs9992658) was associated with HDL-C levels.


Assuntos
Compostos Benzidrílicos , Fenóis , Pessoa de Meia-Idade , Idoso , Humanos , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/urina , Fenóis/toxicidade , Fenóis/urina , Metabolismo dos Lipídeos/genética , Lipídeos
8.
Int J Cancer ; 153(2): 278-289, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-36946647

RESUMO

Serum 25-hydroxyvitamin D (25(OH)D) has been demonstrated to be associated with risk of colorectal cancer (CRC). However, it remains unclear whether this association was modified by vitamin D-related polymorphisms. We evaluated association of serum 25(OH)D concentration with CRC risk among 403 170 participants from UK Biobank Project. Two variants of vitamin D binding protein (VDBP), rs4588 and rs7041, were included to estimate the binding affinity of 25(OH)D to VDBP, and three variants of vitamin D receptor (VDR), rs11568820, rs2228570 and rs1544410, which may influence VDR activity, were also investigated. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 4 957 677 person-years of follow-up, 5053 incident CRC cases were documented. Higher serum 25(OH)D concentrations were significantly associated with lower CRC incidence in a dose-response manner, with HR (95% CIs) being 0.94 (0.91-0.97) per 1 SD increment of serum 25(OH)D level (Ptrend < .001). When separated by anatomic site, we observed a significant association between higher 25(OH)D and lower incidence of colon cancer (Ptrend < .001), but not rectal cancer (Ptrend = .880). The inverse associations between 25(OH)D level and CRC risk were demonstrated in almost all individuals carrying different GC or VDR genotypes, except for those with rs1544410 TT or rs4588 TT genotypes. There was no significant interaction between any single variant, or haplotypes of GC or VDR, and 25(OH)D level. Our findings suggest the potential benefits of maintaining adequate vitamin D for CRC prevention, particularly for tumors from colon.


Assuntos
Neoplasias Colorretais , Polimorfismo de Nucleotídeo Único , Humanos , Vitamina D , Vitaminas , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Genótipo , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Proteína de Ligação a Vitamina D/genética
9.
Crit Rev Food Sci Nutr ; 63(23): 6235-6251, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35068276

RESUMO

Fish and omega-3 polyunsaturated fatty acids (PUFA) have been suggested to play a role in improving cancer prognosis. However, results from epidemiological studies remain inconsistent. Here we assess the association between dietary fish and/or omega-3 PUFAs intake and cancer prognosis with meta-analysis of observational studies. A systematic search of related publications was performed using PubMed and Web of Science databases. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted and then pooled using a random-effect model. Potential linear and non-linear dose-response relationships were explored using generalized least squares estimation and restricted cubic splines. As a result, 21 cohort studies were included in our analysis. Compared to the lowest category, the highest category of fish intake was associated with a significant lower mortality in patients with ovarian cancer (n = 1, HR = 0.74, 95% CI: 0.57-0.95) and overall cancer (n = 12, HR = 0.87, 95% CI: 0.81-0.94). Marine omega-3 PUFAs intake rather than total omega-3 PUFAs intake showed significant protective effects on survival of overall cancer (n = 8, HR = 0.81, 95% CI: 0.71-0.94), in particular prostate cancer (n = 2, HR = 0.62, 95% CI: 0.46-0.82). Dose-response meta-analysis indicated a nonlinear and a linear relationship between fish intake, as well as marine omega-3 PUFAs intake, and overall cancer survival, respectively. In conclusion, our analysis demonstrated a protective effect of dietary fish and marine omega-3 PUFAs consumption on cancer survival.


Assuntos
Ácidos Graxos Ômega-3 , Neoplasias , Masculino , Animais , Alimentos Marinhos , Ácidos Graxos Insaturados , Neoplasias/prevenção & controle , Estudos de Coortes
10.
SLAS Discov ; 28(1): 12-18, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464159

RESUMO

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to play roles in various diseases, yet there is little data on their changes in patients with non-small-cell lung cancer (NSCLC). A simple LC-MS/MS method for EPA and DHA determination is critical to exploring EPA and DHA level changes in NSCLC patients. METHODS: 25 µL of serum was mixed with 25 µL of internal standard working solution, and then 450 µL of acetonitrile for protein precipitation. After vortex and centrifugation, the supernatant was directly used for LC-MS/MS analysis. The method was well validated with linearity, precision, recovery, and matrix effect. The concentrations of EPA and DHA in serum samples from 211 NSCLC patients and 227 healthy controls were determined by this LC-MS/MS method. RESULTS: Good separation and reliable quantification of EPA and DHA in serum samples were achieved by our method. Compared with healthy controls, serum EPA and DHA were significantly reduced in both adenocarcinoma and squamous cell carcinoma patients. The concentrations of EPA and DHA showed a progressive decrease in healthy controls, early- and advanced-stage NSCLC patients. CONCLUSIONS: This study identified significant reductions in serum EPA and DHA in NSCLC patients through the development of an LC-MS/MS method.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Ácido Eicosapentaenoico/análise , Ácidos Docosa-Hexaenoicos/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos
11.
Lab Med ; 54(3): 291-298, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-36239637

RESUMO

OBJECTIVE: This study aimed to validate the performance of modified Japanese Association for Acute Medicine (m-JAAM) and simplified Japanese Society on Thrombosis and Hemostasis (s-JSTH) criteria in diagnosing coagulation disorders in sepsis and examine their prognostic value compared with sepsis-induced coagulopathy (SIC) and International Society on Thrombosis and Hemostasis (ISTH) criteria. METHODS: This retrospective study included subjects diagnosed with sepsis (August 2020 to February 2021, n = 296). The m-JAAM, s-JSTH, SIC, and ISTH criteria were evaluated and compared using receiver operating characteristic (ROC) curves and areas under the curve (AUCs). RESULTS: There was no significant difference in AUC for predicting in-hospital 28-day mortality by m-JAAM, s-JSTH, SCI, and ISTH criteria (0.745, 0.763, 0.760, and 0.730, respectively). The proportion of patients fulfilling the m-JAAM and SIC criteria was higher than that of the s-JSTH and ISTH criteria (43.2%, 56.1% vs. 25.0%, 22.6%, P < .05). CONCLUSION: The m-JAAM criteria might be more suitable for early-stage disseminated intravascular coagulation of sepsis than s-JSTH criteria.


Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Intravascular Disseminada , Sepse , Trombose , Humanos , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/complicações , Estudos Retrospectivos , Trombose/complicações , Sepse/complicações , Sepse/diagnóstico , Unidades de Terapia Intensiva
12.
Am J Respir Crit Care Med ; 207(2): 173-182, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-35943859

RESUMO

Rationale: The individual effects of early-life tobacco smoke exposure and its interactions with genetic factors on lung cancer in adulthood remain unclear. Objectives: To investigate the associations of early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) with lung cancer incidence and mortality. Methods: A total of 432,831 participants from the UK Biobank study were included. We estimated the associations of in utero exposure to tobacco smoke, the age of smoking initiation and their interactions with PRSs with lung cancer incidence and mortality in adulthood using Cox proportional hazard models. Measurements and Main Results: Lung cancer incidence (hazard ratio [HR]: 1.59, 95% confidence interval [CI], 1.44-1.76) increased among participants with in utero tobacco exposure. Multivariable-adjusted HRs (with 95% CIs) of lung cancer incidence for smoking initiation in adulthood, adolescence, and childhood (versus never-smokers) were 6.10 (5.25-7.09), 9.56 (8.31-11.00), and 15.15 (12.90-17.79) (Ptrend < 0.001). Similar findings were observed in lung cancer mortality. Participants with high PRSs and in utero tobacco exposure (versus low PRSs participants without in utero exposure) had an HR of 2.35 for lung cancer incidence (95% CI, 1.97-2.80, Pinteraction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction = 0.032). High PRSs with smoking initiation in childhood (versus never-smokers with low PRSs) had HRs of 18.71 for incidence (95% CI, 14.21-24.63, Pinteraction = 0.004) and 19.74 for mortality (95% CI, 14.98-26.01, Pinteraction = 0.033). Conclusions: In utero and childhood/adolescence exposure to tobacco smoke and its interaction with genetic factors may substantially increase the risks of lung cancer incidence and mortality in adulthood.


Assuntos
Neoplasias Pulmonares , Poluição por Fumaça de Tabaco , Humanos , Adolescente , Poluição por Fumaça de Tabaco/efeitos adversos , Incidência , Nicotiana , Fatores de Risco , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética
13.
Cancer Sci ; 114(2): 680-689, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36310111

RESUMO

This study was performed to characterize the metabolic alteration of non-small-cell lung cancer (NSCLC) and discover blood-based metabolic biomarkers relevant to lung cancer detection. An untargeted metabolomics-based approach was applied in a case-control study with 193 NSCLC patients and 243 healthy controls. Serum metabolomics were determined by using an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. We screened differential metabolites based on univariate and multivariate analysis, followed by identification of the metabolites and related pathways. For NSCLC detection, machine learning was employed to develop and validate the model based on the altered serum metabolite features. The serum metabolic pattern of NSCLC was definitely different from the healthy condition. In total, 278 altered features were found in the serum of NSCLC patients comparing with healthy people. About one-fifth of the abundant differential features were identified successfully. The altered metabolites were enriched in metabolic pathways such as phenylalanine metabolism, linoleic acid metabolism, and biosynthesis of bile acids. We demonstrated a panel of 10 metabolic biomarkers which representing excellent discriminating capability for NSCLC discrimination, with a combined area under the curve (AUC) in the validation set of 0.95 (95% CI: 0.91-0.98). Moreover, this model showed a desirable performance for the detection of NSCLC at an early stage (AUC = 0.95, 95% CI: 0.92-0.97). Our study offers a perspective on NSCLC metabolic alteration. The finding of the biomarkers might shed light on the clinical detection of lung cancer, especially for those cancers in an early stage in Chinese population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Espectrometria de Massas em Tandem , Estudos de Casos e Controles , Metabolômica/métodos , Biomarcadores
14.
Nutrients ; 14(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36364707

RESUMO

The impact of artificially sweetened beverages (ASBs), alternatives to sugar-sweetened beverages, on cancer incidence remains controversial. We conducted a meta-analysis of prospective studies to assess the association of daily ASB intake with cancer risk. A systematic search was performed between January 1967 and September 2022. Risk ratios (RR) or hazard ratios (HR) were extracted and pooled. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used for the assessment of the certainty of evidence. The study was registered at PROSPERO (CRD42022312171). Overall, 14 articles with 17 cohorts were included. There was no significant association between daily ASB consumption and risk of overall cancer (highest versus lowest category: n = 17, RR = 1.03, 95% CI: 0.96-1.11, p = 0.407). For site-specific cancer analysis, the risk of non-lymphoid leukemia was elevated with high ASB intake (n = 3, RR = 1.35, 95% CI: 1.03-1.77, p = 0.030), while risk of colorectal cancer was decreased (n = 3, RR = 0.78, 95% CI: 0.62-0.99, p = 0.037). Dose-response analysis indicated a positive linear association between ASB intake and the risk of leukemia (p-linear = 0.027). The risk increased by 15% per one serving (355 mL) daily ASB intake increment (RR = 1.15, 95% CI: 1.02-1.30). In conclusion, ASB consumption might be positively associated with the risk of leukemia and negatively associated with the risk of colorectal cancer.


Assuntos
Neoplasias Colorretais , Leucemia , Humanos , Bebidas Adoçadas Artificialmente/efeitos adversos , Edulcorantes/efeitos adversos , Estudos Prospectivos , Bebidas/efeitos adversos
15.
PeerJ ; 10: e13272, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469201

RESUMO

Background: Previous studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways. Methods: The concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified. Results: The concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74-0.85]) in the training data set and 0.79 (95%CI [0.71-0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68-0.81]) and 0.86 (95% CI [0.82-0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85-0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71-0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis. Conclusions: The levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Tripsina , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Cromatografia Líquida , Estudos de Casos e Controles , População do Leste Asiático , Neoplasias Pulmonares/diagnóstico , Espectrometria de Massas em Tandem , Aminoácidos , Ácido Glutâmico , Carcinoma de Células Escamosas/diagnóstico
16.
Eur J Nutr ; 61(4): 2115-2127, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35034169

RESUMO

PURPOSE: There is considerable inconsistency in results regarding the association of dietary glycemic index (GI) and glycemic load (GL) with cancer risk. We therefore conducted this systematic review and dose-response meta-analysis of prospective cohort studies to evaluate the relationship between dietary GI/GL and cancer risk. METHODS: We searched PubMed and Web of Science for prospective cohort studies of dietary GI/GL in relation to risks of all types of cancer up to 31 March 2021. We used a random-effect model to calculate summary relative risks (RR) and 95% confidence intervals (CI). The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. This study was registered at PROSPERO (CRD42020215338). RESULTS: Overall, 55 cohorts were included in the meta-analysis. We assessed the relationship between dietary GI or GL and risks of 23 cancer types, including hormone-related cancers, cancers from digestive system, respiratory system, urinary system and other cancer sites. High GI diet increased overall risk of cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.04, 95% CI 1.01-1.07). For site-specific cancers, high GI diet increased risks of lung cancer (highest vs lowest categories, n = 5, RR 1.08, 95% CI 1.01-1.18) and breast cancer (highest vs lowest categories, n = 14, RR 1.05, 95% CI 1.01-1.09), especially for postmenopausal breast cancer (highest vs lowest categories, n = 10, RR 1.06, 95% CI 1.00-1.13), all with low certainty of evidence. Additionally, dietary GI was positively related to risk of bladder cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.23, 95% CI 1.09-1.40), as well as negatively related to ovarian cancer risk with very low certainty of evidence (highest vs lowest categories, n = 4, RR 0.83, 95% CI 0.69-1.00) and lymphoma risk with low certainty of evidence (highest vs lowest categories, n = 2, RR 0.84, 95% CI 0.72-0.98). Besides, we found an inverse association of dietary GL with lung cancer risk with low certainty of evidence (highest vs lowest categories, n = 5, RR 0.87, 95% CI 0.80-0.94). CONCLUSION: High dietary GI increased overall cancer risk with low certainty of evidence. For site-specific cancers, high GI diet increased the risks of breast cancer with low certainty of evidence and lung cancer with low certainty of evidence. Dietary GL was inversely associated with lung cancer risk with low certainty of evidence.


Assuntos
Neoplasias da Mama , Carga Glicêmica , Neoplasias Pulmonares , Glicemia , Neoplasias da Mama/epidemiologia , Dieta , Carboidratos da Dieta/efeitos adversos , Feminino , Índice Glicêmico , Humanos , Estudos Prospectivos , Fatores de Risco
17.
Sci Total Environ ; 807(Pt 1): 150753, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34619205

RESUMO

BACKGROUND: Bisphenols and triclosan (TCS) are common endocrine disrupters (EDCs) that may induce oxidative stress. However, there is limited information as to whether these EDCs interact with genetic variants to modify the levels of oxidative stress on a genome-wide scale. METHODS: We first performed a genome-wide scan among a Chinese population and also measured three urinary EDCs, including bisphenol A (BPA), bisphenol F (BPF) and TCS, and three urinary oxidative stress markers [4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F2α (8-isoPGF2α) and 8-hydroxy-deoxyguanosine (8-OHdG)]. Subsequently, we examined interactions between three urinary EDCs and nearly 4.6 million genetic variants for three urinary oxidative stress markers by the general linear model. RESULTS: Urinary BPA, BPF and TCS were positively associated with HNE-MA, 8-isoPGF2α and 8-OHdG. Significant rs6855040 (4p15.32/between SNORA75B and QDPR)-BPA, rs1112943 (4q35.1/SNX25)-TCS interactions were associated with the 8-isoPGF2α levels (all P < 5 × 10-8). In addition, rs4656116 (1p22.3/CACL1), rs16958760 (17p11.2/between USP43 and DHRS7C) and rs11651078 (17p11.2/LOC339260) showed significant gene-TCS interactions with 8-OHdG (all P < 5 × 10-8). The gene-level analysis found significant interaction between SNX25 and TCS for 8-isoPGF2α levels (P < 2.12 × 10-6). CONCLUSION: Our results identify several gene-EDCs interactions for oxidative stress, highlighting that EDCs may modify the effect of genetic variants on oxidative stress.


Assuntos
Triclosan , 8-Hidroxi-2'-Desoxiguanosina , Compostos Benzidrílicos/toxicidade , Biomarcadores , Estresse Oxidativo , Fenóis , Triclosan/toxicidade
18.
Chemosphere ; 286(Pt 3): 131880, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426286

RESUMO

OBJECTIVE: Bisphenol A (BPA), a common endocrine disrupter, can be activated by cytochrome P450 (CYP) metabolizing enzymes and might influence the development of breast cancer (BC). We hypothesized that BPA could interact with CYP genes, synergistically contributing to the BC risk. METHODS: Urinary BPA was measured in a total of 302 newly diagnosed BC patients and 302 healthy controls by ultra-high performance liquid chromatography-high resolution mass spectrometry. A set of seven CYP gene polymorphisms was genotyped by using the Sequenom MassARRAY system. A multivariate logistic regression model was used to assess the associations of BPA and BPA-SNP interaction with BC risk. RESULTS: BC patients had a higher urinary BPA concentration than healthy individuals (P < 0.001). Each 1-unit increase in log-transformed urinary BPA was associated with a 54 % increased BC risk [95 % confidence interval (CI), 1.34-1.77, P < 0.001]. Individuals with the CYP19A1 rs1902580 GA + AA genotype showed a significantly higher BC risk than those with the GG genotype (OR = 1.45, 95 % CI, 1.01-2.09, P < 0.05). A significant BPA-CYP17A1 rs743572 interaction was found to be associated with a higher risk of BC (Pinteraction = 0.020). Compared with low-BPA individuals carrying CYP17A1 rs743572 GG genotypes, high-BPA individuals with the GA + AA genotype had a higher BC risk, with an odds ratio of 2.49 (95 % CI, 1.52-4.13, P < 0.05). CONCLUSIONS: The positive association of BPA exposure with BC risk might be modified by CYP17A1 rs743572, providing evidence for the interaction effect of environment-genes on the etiology of BC.


Assuntos
Neoplasias da Mama , Compostos Benzidrílicos , Neoplasias da Mama/genética , Estudos de Casos e Controles , Feminino , Humanos , Fenóis , Esteroide 17-alfa-Hidroxilase/genética
19.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663731

RESUMO

The genetic origins of nanoscale extracellular vesicles in our body fluids remains unclear. Here, we perform a tracking analysis of urinary exosomes via RNA sequencing, revealing that urine exosomes mostly express tissue-specific genes for the bladder and have close cell-genetic relationships to the endothelial cell, basal cell, monocyte, and dendritic cell. Tracking the differentially expressed genes of cancers and corresponding enrichment analysis show urine exosomes are intensively involved in immune activities, indicating that they may be harnessed as reliable biomarkers of noninvasive liquid biopsy in cancer genomic diagnostics and precision medicine.


Assuntos
Exossomos/metabolismo , Neoplasias/patologia , Urina , Humanos , Biópsia Líquida , Neoplasias/metabolismo
20.
Carcinogenesis ; 42(11): 1347-1356, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34665859

RESUMO

Substantial evidence highlighted the critical role of long non-coding RNAs (lncRNA) in driving hepatocarcinogenesis. We hypothesized that functional variants in genome-wide association studies (GWASs) associated loci might alter the expression levels of lncRNAs and contribute to the development of hepatocellular carcinoma (HCC). Here, we prioritized potentially cis-expression quantitative trait loci-based single nucleotide polymorphism (SNP)-lncRNA association together with the physical interaction by the analyses from Hi-C data in GWAS loci of chronic hepatitis B and HCC. Subsequently, by leveraging two-stage case-control study (1738 hepatitis B [HBV]) related HCC cases and 1988 HBV persistent carriers) and biological assays, we identified that rs2647046 was significantly associated with HCC risk (odds ratio = 1.26, 95% CI = 1.11 to 1.43, P = 4.14 × 10-4). Luciferase reporter assays and electrophoretic mobility shift assays showed that rs2647046 A allele significantly increased transcriptional activity via influencing transcript factor binding affinity. Allele-specific chromosome conformation capture assays revealed that enhancer with rs2647046 interacted with the HLA-DQB1-AS1 promoter to allele-specifically influence its expression by CTCF-mediated long-range loop. Cell proliferation assays indicated that HLA-DQB1-AS1 is a potential oncogene in HCC. Our study showed HLA-DQB1-AS1 regulated by a causal SNP in a long-range interaction manner conferred the susceptibility to HCC, suggesting an important mechanism of modulating lncRNA expression for risk-associated SNPs in the etiology of HCC.


Assuntos
Elementos Antissenso (Genética)/genética , Carcinoma Hepatocelular/genética , Elementos Facilitadores Genéticos , Cadeias beta de HLA-DQ/metabolismo , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Cadeias beta de HLA-DQ/genética , Humanos , Neoplasias Hepáticas/patologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...