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PURPOSE: Simultaneous profiling of cell-free DNA (cfDNA) methylation and fragmentation features to improve the performance of cfDNA-based cancer detection is technically challenging. We developed a method to comprehensively analyze multimodal cfDNA genomic features for more sensitive esophageal squamous cell carcinoma (ESCC) detection. MATERIALS AND METHODS: Enzymatic conversion-mediated whole-methylome sequencing was applied to plasma cfDNA samples extracted from 168 patients with ESCC and 251 noncancer controls. ESCC characteristic cfDNA methylation, fragmentation, and copy number signatures were analyzed both across the genome and at accessible cis-regulatory DNA elements. To distinguish ESCC from noncancer samples, a first-layer classifier was developed for each feature type, the prediction results of which were incorporated to construct the second-layer ensemble model. RESULTS: ESCC plasma genome displayed global hypomethylation, altered fragmentation size, and chromosomal copy number alteration. Methylation and fragmentation changes at cancer tissue-specific accessible cis-regulatory DNA elements were also observed in ESCC plasma. By integrating multimodal genomic features for ESCC detection, the ensemble model showed improved performance over individual modalities. In the training cohort with a specificity of 99.2%, the detection sensitivity was 81.0% for all stages and 70.0% for stage 0-II. Consistent performance was observed in the test cohort with a specificity of 98.4%, an all-stage sensitivity of 79.8%, and a stage 0-II sensitivity of 69.0%. The performance of the classifier was associated with the disease stage, irrespective of clinical covariates. CONCLUSION: This study comprehensively profiles the epigenomic landscape of ESCC plasma and provides a novel noninvasive and sensitive ESCC detection approach with genome-scale multimodal analysis.
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Ácidos Nucleicos Libres de Células , Metilación de ADN , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Carcinoma de Células Escamosas de Esófago/genética , Anciano , EpigenomaRESUMEN
OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.
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Metabolómica , Humanos , Metabolómica/métodos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/metabolismo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/diagnóstico , Metaboloma/fisiología , Estudios de Casos y Controles , Unión Esofagogástrica/patología , Unión Esofagogástrica/metabolismoRESUMEN
The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.
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Biomarcadores de Tumor , Neoplasias Esofágicas , Compuestos Orgánicos Volátiles , Humanos , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/sangre , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/sangre , Aprendizaje Automático , Curva ROC , Cromatografía de Gases y Espectrometría de Masas/métodos , Estudios de Casos y Controles , Espectrometría de Movilidad Iónica/métodos , Adulto , Detección Precoz del Cáncer/métodos , Sensibilidad y EspecificidadRESUMEN
Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on overall survival (OS) in patients with esophageal carcinoma remains unclear. Thus, we examined these associations among patients with postoperative staged T3N0M0 esophageal carcinoma. The data of 246 patients with postoperative staged T3N0M0 esophageal carcinoma from January 1, 2010, to December 31, 2022, were retrospectively analyzed. OS was measured from the date of pathological diagnosis until either death or the last follow-up. The Kaplan-Meier method and multivariate Cox regression model were used to analyze the relationship between neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Platelet-to-lymphocyte ratio (LMR), SII, PNI, and OS. The predictive value of SII and PNI as a combined index was analyzed by the receiver operating characteristic curve (ROC). A total of 246 patients aged 65.5â ±â 7.4 years were included in this study and 181 (73.6%) were male. The univariate analysis revealed that differentiation, vessel involvement, postoperative treatment, NLR, SII, PLR, LMR, PNI were predictors of OS (Pâ <â .05). After adjusted for potential confounds, multivariate Cox regression analysis showed that the differentiation, SII, PNI, and postoperative treatment were independent prognostic factors correlated with OS in patients with postoperative staged T3N0M0 esophageal carcinoma (Pâ <â .05). SII and PNI, as a combined indicator, have a higher predictive value for OS. The NLR, SII, PLR, LMR, and PNI could all be used as independent predictors of OS in patients with postoperative staged T3N0M0 esophageal carcinoma. The combination of SII and PNI can significantly improve the accuracy of prediction.
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Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Masculino , Femenino , Anciano , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Neutrófilos , Evaluación Nutricional , Recuento de Linfocitos , Estimación de Kaplan-Meier , Periodo Preoperatorio , Recuento de Plaquetas , Curva ROC , Linfocitos , Modelos de Riesgos Proporcionales , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Esophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer. METHODS: Overall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan-Meier method. RESULTS: Preoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer. CONCLUSION: Plasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.
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Neoplasias Esofágicas , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Biomarcadores de Tumor/sangre , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , EsofagectomíaRESUMEN
Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.
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Biomarcadores de Tumor , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Biomarcadores de Tumor/sangre , Inflamación/sangre , Adenocarcinoma/sangre , Adenocarcinoma/diagnóstico , Pronóstico , Masculino , Femenino , Citocinas/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear. PURPOSE: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis. METHODS: Genome-wide association studies (GWASs) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWAS of esophageal cancer specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and ESCA, mediation MR analyses were performed for 1091 blood metabolites and 309 metabolite ratios. RESULTS: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with ESCA but all the 12 gut microbiota metabolic pathways with ESCA indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to ESCA. CONCLUSION: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and ESCA.
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Neoplasias Esofágicas , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/microbiología , Neoplasias Esofágicas/sangre , Microbioma Gastrointestinal/genética , MetabolomaRESUMEN
BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.
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Metilación de ADN , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Método Doble Ciego , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/sangre , AdultoRESUMEN
Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (Pï¼0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.
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Ácidos Nucleicos Libres de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Lesiones Precancerosas/sangre , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Ácidos Nucleicos Libres de Células/sangre , Detección Precoz del Cáncer/métodos , Biomarcadores de Tumor/sangre , Masculino , Femenino , Carcinoma in Situ/sangre , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/genética , Carcinoma in Situ/patologíaRESUMEN
PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.
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Biomarcadores de Tumor , Ácidos Nucleicos Libres de Células , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/sangre , Estimación de Kaplan-Meier , Supervivencia sin Progresión , Carcinoma de Células Escamosas de Esófago/radioterapia , Carcinoma de Células Escamosas de Esófago/sangre , Adulto , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/mortalidad , Anciano de 80 o más Años , CinéticaRESUMEN
PURPOSE: In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. MATERIALS AND METHODS: We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2amp versus FGFR2null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2amp GECs. RESULTS: Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2amp. The most commonly co-occurring gene mutations were TP53, CTNNB1, CDH1, and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. CONCLUSION: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers.
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ADN Tumoral Circulante , Neoplasias Esofágicas , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Neoplasias Gástricas , Humanos , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , AdultoRESUMEN
Background: Esophageal squamous cell carcinoma (ESCC) is highly prevalent and has a high mortality rate. Traditional diagnostic methods, such as imaging examinations and blood tumor marker tests, are not effective in accurately diagnosing ESCC due to their low sensitivity and specificity. Esophageal endoscopic biopsy, which is considered as the gold standard, is not suitable for screening due to its invasiveness and high cost. Therefore, this study aimed to develop a convenient and low-cost diagnostic method for ESCC using plasma-based lipidomics analysis combined with machine learning (ML) algorithms. Methods: Plasma samples from a total of 40 ESCC patients and 31 healthy controls were used for lipidomics study. Untargeted lipidomics analysis was conducted through liquid chromatography-mass spectrometry (LC-MS) analysis. Differentially expressed lipid features were filtered based on multivariate and univariate analysis, and lipid annotation was performed using MS-DIAL software. Results: A total of 99 differential lipids were identified, with 15 up-regulated lipids and 84 down-regulated lipids, suggesting their potential as diagnostic targets for ESCC. In the single-lipid plasma-based diagnostic model, nine specific lipids (FA 15:4, FA 27:1, FA 28:7, FA 28:0, FA 36:0, FA 39:0, FA 42:0, FA 44:0, and DG 37:7) exhibited excellent diagnostic performance, with an area under the curve (AUC) exceeding 0.99. Furthermore, multiple lipid-based ML models also demonstrated comparable diagnostic ability for ESCC. These findings indicate plasma lipids as a promising diagnostic approach for ESCC.
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Biomarcadores de Tumor , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lipidómica , Humanos , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/diagnóstico , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , Masculino , Lipidómica/métodos , Femenino , Biomarcadores de Tumor/sangre , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Aprendizaje Automático , Lípidos/sangre , Cromatografía Liquida , Estudios de Casos y ControlesRESUMEN
BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.
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Fuga Anastomótica , Biomarcadores , Proteína C-Reactiva , Esofagectomía , Humanos , Fuga Anastomótica/sangre , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/sangre , Esofagectomía/efectos adversos , Recuento de Leucocitos , Valor Predictivo de las Pruebas , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnósticoRESUMEN
BACKGROUND: To further clarify the predictive value of pretreatment Naples prognostic score (NPS), calculating based on the serum albumin concentration, total cholesterol level, neutrophil to lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR), among esophageal cancer patients based on available evidence. METHODS: The PubMed, EMBASE, Web of Science and CNKI databases were searched up to December 1, 2023 for relevant studies. Overall survival (OS), progression-free survival (PFS) and cancer-specific survival (CSS) were endpoints and the hazard ratio (HR) with 95% confidence interval (CI) was combined to evaluate the predictive role of NPS for survival. Subgroup analysis based on pathological type and treatment were further conducted. RESULTS: Ten retrospective studies with 2250 cases were included in our analysis. Pooled results demonstrated that higher pretreatment NPS predicted poorer OS (HRâ =â 2.24, 95% CI: 1.57-3.20, Pâ <â .001), PFS (HRâ =â 3.03, 95% CI: 1.84-4.98, Pâ <â .001) and CSS (HRâ =â 2.90, 95% CI: 1.80-4.68, Pâ <â .001). Then subgroup analysis for the OS and PFS stratified by the pathological type (squamous cell carcinoma vs esophageal cancer) and treatment (surgery vs non-surgery) were further conducted, which showed similar results. CONCLUSION: Pretreatment NPS is significantly associated with prognosis in esophageal cancer and higher NPS predicts worse survival among patients with esophageal cancer.
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Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/sangre , Pronóstico , Albúmina Sérica/análisis , Neutrófilos , Colesterol/sangre , Valor Predictivo de las Pruebas , Linfocitos , Monocitos , Estudios RetrospectivosRESUMEN
Lipids participate in many important biological functions through energy storage, membrane structure stabilization, signal transduction, and molecular recognition. Previous studies have shown that patients with esophageal squamous cell carcinoma (ESCC) have abnormal lipid metabolism. However, studies characterizing lipid metabolism in ESCC patients through lipidomics are limited. Plasma lipid profiles of 65 ESCC patients and 42 healthy controls (HC) were characterized by lipidomics-based ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Single-factor and multi-factor statistical analysis were used to screen the differences in blood lipids between groups, and combined with component ratio analysis and receiver operating characteristic (ROC) curve diagnostic efficiency assessment, to reveal the potential mechanisms and biomarkers of ESCC. There were significant differences in lipid profiles between the ESCC and HC groups. Thirty-six differential lipids (11 up-regulated and 25 down-regulated) were selected based on the criteria of p < .05 and fold change > 1.3 or < 0.77. Glycerophospholipids were the major differential lipids, suggesting that these lipid metabolic pathways exhibit a significant imbalance that may contribute to the development of esophageal squamous cell carcinoma. Among them, the seven candidate biomarkers for esophageal squamous cell carcinoma with the highest diagnostic value are three phosphatidylserine (PS), three fatty acids (FA) and one phosphatidylcholine (PC).
Asunto(s)
Biomarcadores de Tumor , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lipidómica , Humanos , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/sangre , Masculino , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/metabolismo , Lipidómica/métodos , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/sangre , Estudios de Casos y Controles , Anciano , Metabolismo de los Lípidos , Lípidos/sangre , Curva ROC , Glicerofosfolípidos/sangre , Fosfatidilserinas/metabolismo , Fosfatidilserinas/sangre , Ácidos Grasos/sangreRESUMEN
Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1ß), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1ß, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1ß, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.
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Índice de Masa Corporal , Citocinas , Progresión de la Enfermedad , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Pérdida de Peso , Humanos , Masculino , Femenino , Persona de Mediana Edad , Citocinas/sangre , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Estudios Retrospectivos , Anciano , Terapia Neoadyuvante/métodos , Desnutrición/sangre , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias , Quimioradioterapia/métodos , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND/AIM: The albumin to fibrinogen ratio (AFR) has been identified as a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of AFR in esophageal cancer patients who received curative resection. PATIENTS AND METHODS: The present study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters were compared between patients with high and low AFRs. RESULTS: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed when using a pretreatment AFR of 1.23. When comparing the patient backgrounds between the high-AFR (AFR ≥12.3) and low-AFR (AFR<12.3) groups, significant differences were noted in the pathological T status. The high-AFR group had significantly higher OS rates at 3 years (70.8%) and 5 years (59.3%) after surgery in comparison to the low-AFR group (46.6% and 37.4%, respectively). Univariate and multivariate analyses for OS showed that the AFR was a significant prognostic factor. In addition, when comparing the site of first recurrence, a marginally significant difference was noted in hematological recurrence. CONCLUSION: The AFR is a significant risk factor in patients with esophageal cancer, holding promise as a valuable prognostic factor.
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Neoplasias Esofágicas , Fibrinógeno , Humanos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Masculino , Femenino , Fibrinógeno/metabolismo , Persona de Mediana Edad , Anciano , Pronóstico , Biomarcadores de Tumor/sangre , Albúmina Sérica/análisis , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Anciano de 80 o más Años , AdultoAsunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inmunoterapia , Humanos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/terapia , Inmunoterapia/métodos , Valor Predictivo de las Pruebas , Biomarcadores de Tumor/sangreRESUMEN
BACKGROUND/AIM: Recently, the prognostic immune and nutritional index (PINI) was developed and reported to be a promising nutritional and inflammatory prognostic marker. The aim of the present study was to clarify the clinical impact of the PINI for esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: We conducted a retrospective review of medical records and collected data on consecutive esophageal cancer patients who underwent curative resection at Yokohama City University between 2005 and 2020. The PINI was calculated by dividing the serum ALB concentration (g/dl) by the serum monocyte concentration, both of which were measured before surgery. RESULTS: A total of 180 patients were included in this study. The cutoff value of the PINI was 3.0 in the present study. The 3- and 5-year overall survival rates were 45.2% and 33.5%, respectively, in the PINI-low subgroup, and 69.1% and 61.8%, respectively, in the PINI-high subgroup. A multivariate analysis demonstrated that the PINI was an independent prognostic factor for overall survival (hazard ratio=2.091, 95% confidence interval=1.287-3.399, p=0.003). Similar results were observed for recurrence-free survival. When comparing the sites of recurrence between the two groups, the incidence of hematological recurrence was significantly greater in the PINI-low subgroup compared to the PINI-high subgroup (46.8% vs. 21.1%, p<0.001). CONCLUSION: The PINI is a promising nutritional and inflammatory marker for esophageal cancer patients. The PINI might be a useful marker for the treatment and management of esophageal cancer patients.
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Neoplasias Esofágicas , Evaluación Nutricional , Humanos , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/cirugía , Masculino , Femenino , Pronóstico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Estado Nutricional , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , AdultoRESUMEN
BACKGROUND: The application of liquid biopsy analysis utilizing circulating tumor DNA (ctDNA) has gained prominence as a biomarker in specific cancer types. Nevertheless, the correlation between ctDNA and the prognostic outcomes of patients with esophageal cancer (EC) remains a subject of controversy. This meta-analysis aims to assess the correlation between ctDNA and the prognosis of EC patients. METHODS: The authors systematically explored Embase, PubMed, and the Cochrane Database to identify studies reporting on the prognostic value of ctDNA in EC patients before November 2023. The primary outcome involved the determine of associations between ctDNA with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS), as well asprogression-free survival (PFS) among EC patients. Secondary outcomes encompassed a detailed subgroup analysis in the setting of EC, including parameters such as detection time, histological subtypes, treatment modalities, regions, anatomic locations, and detection methods. Publication bias was assessed utilizing Begg's test, Egger's test, and funnel plots. A sensitivity analysis was conducted by systematically excluding individual studies to evaluate the stability of the results. RESULTS: A total of 1203 studies were initially screened, from which 13 studies underwent further analysis, encompassing 604 patients diagnosed with EC. The comprehensive pooled analysis indicated a significant association between the detection of ctDNA and poor OS (HR: 3.65; 95% CI: 1.97-6.75, P <0.001), DFS/RFS (HR: 6.08; 95% CI: 1.21-30.50, P <0.001), and PFS (HR: 2.84; 95% CI: 1.94-4.16, P <0.001). Subgroup analysis showed that ctDNA remained a consistent negative predictor of OS when stratified by different detection time, histological subtypes, regions, anatomic locations, and detection methods. Furthermore, subgroup analysis stratified by regions and study types demonstrated an association between ctDNA detection and poor PFS in EC patients. CONCLUSION: Our results indicate plasma ctDNA may serve as robust prognostic markers for OS, DFS/RFS, and PFS among EC patients. This finding suggests that plasma ctDNA could offer a highly effective approach for risk stratification and personalized medicine.