RESUMO
We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.
Assuntos
Biomarcadores Tumorais , Metaloproteinase 13 da Matriz , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Metaloproteinase 13 da Matriz/sangue , Idoso , Curva ROC , Adulto , Estudos de Casos e Controles , Detecção Precoce de Câncer/métodosRESUMO
Our previous study showed that levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) has potential diagnostic value for early-stage upper gastrointestinal cancers. This study aimed to assess whether serum IGFBP-1 is a potential diagnostic and prognostic biomarker for CRC patients. IGFBP-1 mRNA expression profile data of peripheral blood in colorectal cancer (CRC) patients were downloaded and analyzed from Gene Expression Omnibus database. We detected serum IGFBP-1 in 138 CRC patients and 190 normal controls using enzyme-linked immunosorbent assay. Blood IGFBP-1 mRNA levels were higher in CRC patients than those in normal controls (P = 0.027). In addition, serum IGFBP-1 protein levels in the CRC group were significantly higher than those in normal control group (P < 0.0001). Serum IGFBP-1 demonstrated better diagnostic accuracy for all CRC and early-stage CRC, respectively, when compared with carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA 19-9) or the combination of CEA and CA19-9. Furthermore, Cox multivariate analysis revealed that serum IGFBP-1 was an independent prognostic factor for OS (HR = 2.043, P = 0.045). Our study demonstrated that serum IGFBP-1 might be a potential biomarker for the diagnosis and prognosis of CRC. In addition, the nomogram might be helpful to predict the prognosis of CRC.
Assuntos
Neoplasias Colorretais , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina , Humanos , Antígeno Carcinoembrionário , Prognóstico , RNA Mensageiro , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genéticaRESUMO
The parameters for survival prediction of esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiotherapy (NCRT) combined with surgery are unclear. Here, we aimed to construct a nomogram for survival prediction of ESCC patients treated with NCRT combined with surgery based on pretreatment serological hepatic and renal function tests. A total of 174 patients diagnosed as ESCC were enrolled as a training cohort from July 2007 to June 2019, and approximately 50% of the cases (n = 88) were randomly selected as an internal validation cohort. Univariate and multivariate Cox survival analyses were performed to identify independent prognostic factors to establish a nomogram. Predictive accuracy of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration curve. ALT, ALP, TBA, TP, AST, TBIL and CREA were identified as independent prognostic factors and incorporated into the construction of the hepatic and renal function test nomogram (HRFTNomogram). The C-index of the HRFTNomogram for overall survival (OS) was 0.764 (95% CI 0.701-0.827) in the training cohort, which was higher than that of the TNM staging system (0.507 (95% CI 0.429-0.585), P < 0.001). The 5-year OS calibration curve of the training cohort demonstrated that the predictive accuracy of the HRFTNomogram was satisfactory. Moreover, patients in the high-risk group stratified by the HRFTNomogram had poorer 5-year OS than those in the low-risk group in the training cohort (27.4% vs. 80.3%, P < 0.001). Similar results were observed in the internal validation cohort. A novel HRFTNomogram might help predict the survival of locally advanced ESCC patients treated with NCRT followed by esophagectomy.
RESUMO
Autoantibodies against New York esophageal squamous cell cancer 1 (NY-ESO-1) play a crucial role in the diagnosis of esophageal cancer. In this work, a surface plasmonic tilted fiber Bragg grating (TFBG) biosensor is proposed for the detection of NY-ESO-1 antibody, as well as the investigation of the hook effect (which refers to the false negative result in some immunoassays when the concentration of antibodies in the sample is very high) during biomolecular binding between NY-ESO-1 antigen and antibody. The biosensor is made by an 18° TFBG coated with a 50-nm-thick gold film over the fiber surface together with NY-ESO-1 antigens attached to the metallic surface serving as bio-receptors. This biosensor can provide a limit of detection at a concentration of 2 × 10-7 µg/ml with a good linearity in the range from 2 × 10-7 to 2 × 10-5 µg/ml. For a concentration higher than 2 × 10-3 µg/ml, the performance of the sensor probe is reduced owing to the hook effect. Furthermore, experimental results have also demonstrated the repeatability of the proposed biosensor. This proposed biosensor features label-free, compactness, and fast response, which could be potentially applied in the diagnosis of esophageal cancer.
RESUMO
Electrochemiluminescence nanoprobes with a core-shell-shell structure have been designed and applied for hyaluronidase detection. The nanoprobes can precipitate efficiently through target-regulation wettability for collection, and enrich near to the hydrophobic electrode surface through hydrophobic interaction to enhance the performance of the biosensor.
Assuntos
Técnicas Biossensoriais , Hialuronoglucosaminidase , MolhabilidadeRESUMO
BACKGROUND: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. METHODS: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations. RESULTS: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. CONCLUSIONS: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Análise da Randomização Mendeliana , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Teorema de Bayes , Fatores de Risco , Predisposição Genética para Doença , Aldeído-Desidrogenase Mitocondrial/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Etanol , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Early detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). METHODS: We conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy. RESULTS: Serum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907). CONCLUSIONS: Our study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC.
RESUMO
AIMS: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive and lethal malignancies with an extremely poor prognosis. It is necessary to explore the molecular mechanisms of ESCC invasion. MAIN METHODS: We utilized high-throughput mass spectrometry to analyze the proteomes and phosphorylation profiles of two ESCC cell lines with differing invasion capacities (HK vs TE10). Differentially expressed proteins and phosphorites were identified, followed by comprehensive bioinformatics analyses encompassing function and pathway enrichment, protein-protein interaction (PPI) network analysis, hub gene identification, co-expression analysis, kinase-substrate prediction, and drug-target network analysis. CCK-8 assay, transwell examination, wound-healing assay, and western blot was used to validate the effects of fostamatinib on ESCC cells proliferation, invasion, migration, and LYN expression. KEY FINDINGS: The Q4 cluster of differentially phosphorylated proteins was primarily associated with functions and pathways relevant to tumor metastasis. Phosphorylated hub proteins including ARHGAP35, CTNNA1, and SHC1 were identified through the analysis of PPI network, and their respective regulated kinases were predicted. Among the predicted kinases, LYN was validated to be associated with lymph node metastasis (N0 vs. N1-3) and prognosis in ESCC patients at mRNA levels using TGGA data and protein levels in ESCC tissues (p < 0.05). Validation experiments confirmed the inhibitory effects of fostamatinib on ESCC cells proliferation, migration, invasion, and LYN expression. SIGNIFICANCE: Our multi-omics analysis offers deeper perspectives on ESCC invasiveness and unveils new phosphorylated hub proteins with their regulatory kinase. This study also suggests that fostamatinib may be a potential agent for treating ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteômica , Movimento Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genéticaRESUMO
PURPOSE: Due to the poor and unpredictable prognosis of breast cancer (BC) patients with bone metastasis, it is necessary to find convenient and available prognostic predictors. This study aimed to recognize the clinical and prognostic factors related to clinical laboratory examination and to construct a prognostic nomogram for BC bone metastasis. METHODS: We retrospectively analyzed 32 candidate indicators from clinical features and laboratory examination data of 276 BC patients with bone metastasis. Univariate and multivariate regression analyses were performed to identify significant prognostic factors related to BC with bone metastasis. Nomogram was constructed and estimated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS: Patients were randomly grouped into training (n = 197) and validation cohorts (n = 79). In training cohort, the multivariate regression analysis revealed that age, other organ metastasis sites, serum level of lactate dehydrogenase, globulin, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and monocyte ratio were independent prognostic factors for BC with bone metastasis. The prognostic nomogram in training cohort exhibited areas under the ROC curve (AUCs) of 0.797, 0.782, and 0.794, respectively, for predicting 1-, 3-, and 5-year overall survival. In validation cohort, the nomogram still showed acceptable discrimination ability (AUCs: 0.723, 0.742, and 0.704) and calibration. CONCLUSION: This study constructed a novel prognostic nomogram for BC patients with bone metastasis. It could serve as a potential tool of survival assessment to help individual treatment decision-making for clinicians.
Our study investigated potential prognostic value of indicators from biochemical and blood routine examination for breast cancer patients with bone metastasis.Our study established a nomogram based on the indicators from biochemical and blood routine examination, which might enhance the ability to predict prognosis of breast cancer patients with bone metastasis.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Índices de Eritrócitos , Testes Hematológicos , Prognóstico , Estudos RetrospectivosRESUMO
Backgrounds: Early detection might help in reducing the burden and promoting the survival rate of gastric cancers. Herein, we tried to explore the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in gastric cancers. Methods: In this study, we first analyzed the expression levels and prognostic value of IGFBP7 mRNA in gastric cancers from The Cancer Genome Atlas (TCGA) database. Then, we recruited 169 gastric cancer patients and 100 normal controls as training cohort, and 55 gastric cancer patients and 55 normal controls as independent validation cohort. Enzyme-linked immunosorbent assay was applied to test the serum levels of IGFBP7. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to evaluation the diagnostic value. Results: TCGA showed that IGFBP7 mRNA was dysregulated and associated with prognosis in gastric cancer patients. Then, we examined the expression of serum IGFBP7 and found that serum IGFBP7 expressed lower in gastric cancer patients than normal controls both in training and independent validation cohorts (p < 0.0001). In training cohort, with the cutoff value of 1.515 ng/ml, the AUC for distinguishing gastric cancer patients was 0.774 (95% CI [0.713-0.836]) with sensitivity of 36.7% (95% CI [29.5-44.5]) and specificity of 90.0% (95% CI [82.0-94.8]). As for early-stage EJA, the AUC was 0.773 (95% CI [0.701-0.845]) with the sensitivity of 33.3% (95% CI [14.4-58.8]). In independent validation cohort, with the same cutoff value, the AUC reached to 0.758 (95% CI [0.664-0.852]). Similarly, for early-stage gastric cancer diagnosis in the independent validation cohort, the AUC value was 0.778 (95% CI [0.673-0.882]). Conclusions: This study indicated that serum IGFBP7 might act as a potential early diagnostic marker for gastric cancers.
Assuntos
Neoplasias Gástricas , Humanos , Área Sob a Curva , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , RNA Mensageiro/genética , Neoplasias Gástricas/diagnósticoRESUMO
Background: The incidence of esophagogastric junction adenocarcinoma (EJA) patients was increasing but their prognoses were poor. Blood-based predictive biomarkers were associated with prognosis. This study was to build a nomogram based on preoperative clinical laboratory blood biomarkers for predicting prognosis in curatively resected EJA. Methods: Curatively resected EJA patients, recruited between 2003 and 2017 in the Cancer Hospital of Shantou University Medical College, were divided chronologically into the training (n=465) and validation groups (n=289). Fifty markers, involving sociodemographic characteristics and preoperative clinical laboratory blood indicators, were screened for nomogram construction. Independent predictive factors were selected using Cox regression analysis and then were combined to build a nomogram to predict overall survival (OS). Results: Composed of 12 factors, including age, body mass index, platelets, aspartate aminotransferase-to-alanine transaminase ratio, alkaline phosphatase, albumin, uric acid, IgA, IgG, complement C3, complement factor B and systemic immune-inflammation index, we constructed a novel nomogram for OS prediction. In the training group, when combined with TNM system, it acquired a C-index of 0.71, better than using TNM system only (C-index: 0.62, p < 0.001). When applied in the validation group, the combined C-index was 0.70, also better than using TNM system (C-index: 0.62, p < 0.001). Calibration curves exhibited that the nomogram-predicted probabilities of 5-year OS were both in consistency with the actual 5-year OS in both groups. Kaplan-Meier analysis exhibited that patients with higher nomogram scores contained poorer 5-year OS than those with lower scores (p < 0.0001). Conclusions: In conclusion, the novel nomogram built based on preoperative blood indicators might be the potential prognosis prediction model of curatively resected EJA.
RESUMO
Background: The results regarding the association between insulin-like growth factor binding protein 1 (IGFBP1) expression and cancer risk were controversial. We performed a meta-analysis to provide novel evidence on relationship between IGFBP1 expression and cancer risk. Methods: PubMed, Embase, Cochrane library and Web of science were searched for relevant cohort and case-control studies exploring the relationship between IGFBP1 expression and cancer risk. Odds ratios (ORs) were pooled in this meta-analysis using random model. Subgroup analyses were performed based on ethnicity, tumor types, publication year, study type, Newcastle-Ottawa Scale (NOS) score and sex. Results: A total of 27 studies including 16 cohort and 11 case-control studies were identified by literature search. No significant association was found between IGFBP1 expression and risk of various cancers [0.90, 95% confidence interval (CI): 0.79, 1.03]. The overall results showed that the pooled ORs were 0.71 (95% CI: 0.57, 0.88] for prostate cancer risk and 0.66 (95%CI: 0.44, 0.99) for colorectal cancer (CRC) risk. However, there is no significant association between IGFBP1 expression and risk for ovarian cancer (1.70, 95%CI: 0.41, 6.99), breast cancer (1.02, 95%CI: 0.85, 1.23), endometrial cancer (1.19, 95%CI: 0.64, 2.21), colorectal adenoma (0.93; 95%CI: 0.81, 1.07), lung cancer (0.81, 95%CI: 0.39, 1.68) or multiple myeloma (1.20, 95%CI: 0.98, 1.47). Conclusion: In this study, compared with individuals at low IGFBP1 expression adjusted for age, smoking status, alcohol intake and so on, risk of the prostate cancer and CRC were decreased among individuals of high IGFBP1 expression. There needs further study to confirm this issue.
RESUMO
Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive oral tumors. The aim of this study was to establish a nomogram to predict overall survival (OS) of TSCC patients after surgery. 169 TSCC patients who underwent surgical treatments in the Cancer Hospital of Shantou University Medical College were included. A nomogram based on Cox regression analysis results was established and internally validated using bootstrap resampling method. pTNM stage, age and total protein, immunoglobulin G, factor B and red blood cell count were identified as independent prognostic factors to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of pTNM stage, indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected concordance index of nomogram was higher than that of pTNM stage (0.794 vs. 0.665, p = 0.0008). The nomogram also had a good calibration and improved overall net benefit. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (p < 0.0001). The nomogram based on nutritional and immune-related indicators represents a promising tool for outcome prediction of surgical OTSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Nomogramas , Estadiamento de Neoplasias , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Teorema de Bayes , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Fatores de Risco , Neoplasias de Cabeça e Pescoço/patologiaRESUMO
Objective: The occurrence and development of oesophageal neoplasia (ON) is closely related to hormone changes. The aim of this study was to investigate the causal relationships between age at menarche (AAMA) or age at menopause (AAMO) and benign oesophageal neoplasia (BON) or malignant oesophageal neoplasia (MON) from a genetic perspective. Methods: Genome-wide association study (GWAS) summary data of exposures (AAMA and AAMO) and outcomes (BON and MON) were obtained from the IEU OpenGWAS database. We performed a two-sample Mendelian randomization (MR) study between them. The inverse variance weighted (IVW) was used as the main analysis method, while the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The maximum likelihood, penalized weighted median, and IVW (fixed effects) were validation methods. We used Cochran's Q statistic and Rucker's Q statistic to detect heterogeneity. The intercept test of the MR Egger and global test of MR pleiotropy residual sum and outlier (MR-PRESSO) were used to detect horizontal pleiotropy, and the distortion test of the MR-PRESSO analysis was used to detect outliers. The leave-one-out analysis was used to detect whether the MR analysis was affected by single nucleotide polymorphisms (SNPs). In addition, the MR robust adjusted profile score (MR-RAPS) method was used to assess the robustness of MR analysis. Results: The random-effects IVW results showed that AAMA had a negative genetic causal relationship with BON (odds ratio [OR] = 0.285 [95% confidence interval [CI]: 0.130-0.623], P = 0.002). The weighted median, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with random-effects IVW (P < 0.05). The MR Egger, simple mode and weighted mode results showed that AAMA had no genetic causal relationship with BON (P > 0.05). However, there were no causal genetic relationships between AAMA and MON (OR = 1.132 [95%CI: 0.621-2.063], P = 0.685), AAMO and BON (OR = 0.989 [95%CI: 0.755-1.296], P = 0.935), or AAMO and MON (OR = 1.129 [95%CI: 0.938-1.359], P = 0.200). The MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with a random-effects IVW (P > 0.05). MR analysis results showed no heterogeneity, the horizontal pleiotropy and outliers (P > 0.05). They were not driven by a single SNP, and were normally distributed (P > 0.05). Conclusion: Only AAMA has a negative genetic causal relationship with BON, and no genetic causal relationships exist between AAMA and MON, AAMO and BON, or AAMO and MON. However, it cannot be ruled out that they are related at other levels besides genetics.
Assuntos
Neoplasias Esofágicas , Estudo de Associação Genômica Ampla , Feminino , Humanos , Adolescente , Menarca/genética , Análise da Randomização Mendeliana , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Desenvolvimento do AdolescenteRESUMO
BACKGROUNDS: Preoperative noninvasive tools to predict pretreatment lymph node metastasis (PLNM) status accurately for esophagogastric junction adenocarcinoma (EJA) are few. Thus, the authors aimed to construct a nomogram for predicting PLNM in curatively resected EJA. METHODS: This study enrolled 638 EJA patients who received curative surgery resection and divided them randomly (7:3) into training and validation groups. For nomogram construction, 26 candidate parameters involving 21 preoperative clinical laboratory blood nutrition-related indicators, computed tomography (CT)-reported tumor size, CT-reported PLNM, gender, age, and body mass index were screened. RESULTS: In the training group, Lasso regression included nine nutrition-related blood indicators in the PLNM-prediction nomogram. The PLNM prediction nomogram yielded an area under the receiver operating characteristic (ROC) curve of 0.741 (95 % confidence interval [CI], 0.697-0.781), which was better than that of the CT-reported PLNM (0.635; 95% CI 0.588-0.680; p < 0.0001). Application of the nomogram in the validation cohort still gave good discrimination (0.725 [95% CI 0.658-0.785] vs 0.634 [95% CI 0.563-0.700]; p = 0.0042). Good calibration and a net benefit were observed in both groups. CONCLUSIONS: This study presented a nomogram incorporating preoperative nutrition-related blood indicators and CT imaging features that might be used as a convenient tool to facilitate the preoperative individualized prediction of PLNM for patients with curatively resected EJA.
Assuntos
Adenocarcinoma , Nomogramas , Humanos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Junção Esofagogástrica/diagnóstico por imagem , Junção Esofagogástrica/cirurgia , Metástase Linfática , Tomografia Computadorizada por Raios X/métodosRESUMO
Objective: The primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC). Methods: We conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences. Results: The random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P < 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P < 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis. Conclusion: The findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.
Assuntos
Neoplasias Esofágicas , Refluxo Gastroesofágico , Humanos , Ordem de Nascimento , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/genética , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/genética , Fatores de Proteção , Reprodutibilidade dos Testes , Análise da Randomização MendelianaRESUMO
BACKGROUND: Esophagogastric junction adenocarcinoma (EJA) lacks serum biomarkers to assist in diagnosis and prognosis. Here, we aimed to evaluate the diagnostic and prognostic value of serum insulin-like growth factor binding protein 3 (IGFBP3) in EJA patients. METHODS: 320 participants were recruited from November 2016 to January 2020, who were randomly divided into a training cohort (112 normal controls and 102 EJA patients including 24 early-stage patients) and a validation cohort (56 normal controls and 50 EJA patients including 12 early-stage patients). We used receiver operating characteristics curve (ROC) to evaluate diagnostic value. The predictive performance of the nomogram was evaluated by the concordance index (C-index). RESULTS: Serum IGFBP3 levels were significantly lower in early-stage EJA or EJA patients than those in controls (P < 0.01). Measurement of serum IGFBP3 demonstrated an area under curve of 0.819, specificity 90.18% and sensitivity 43.14% in training cohort. Similar results were observed in validation cohort (0.804, 87.50%, 42.00%). Importantly, serum IGFBP3 had a satisfactory diagnostic value for early-stage EJA (0.822, 90.18%, 45.83% and 0.811, 84.48%, 50.00% in training and validation cohorts, respectively). Furthermore, survival analysis demonstrated that lower serum IGFBP3 level was related to poor prognosis (P < 0.05). Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic factor (HR = 0.468, P = 0.005). Compared with TNM stage, a nomogram based on serum IGFBP3, tumor size and TNM stage indicated an improved C-index in prognostic prediction (0.625 vs. 0.735, P = 0.001). CONCLUSIONS: We found that serum IGFBP3 was a potential diagnostic and prognostic marker of EJA. Meanwhile, the nomogram might predict the prognosis of EJA more accurately and efficiently.
RESUMO
Objectives: At present, esophageal squamous cell carcinoma (ESCC) patients accepting neoadjuvant chemoradiotherapy (nCRT) plus surgery lack corresponding prognostic indicators. This study aimed to construct a prognostic prediction model for ESCC patients undergoing nCRT and surgery based on immune and inflammation-related indicators. Methods: We retrospectively analyzed the levels of serum immune- and inflammation-related indicators of ESCC patients before receiving nCRT plus surgery in the training cohort (99 patients) and validation cohort (67 patients), which were collected from 2007 to 2020. Univariate and multivariate Cox survival analyses were conducted to evaluate the indicators to set up a nomogram associated with the patients' overall survival (OS). The prediction accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), decision curve, calibration curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: Univariate and multivariate Cox analyses demonstrated that immune globin A (IgA) and C-reactive protein (CRP) were independent risk factors. A nomogram based on IgA, CRP, and cTNM stage was established for predicted OS in the training cohort and validated in the validation cohort. The C-index of the nomogram was 0.820 (95% CI: 0.705-0.934), which was higher than that of the cTNM stage (0.655 (95% CI: 0.546-0.764), p < 0.05) in the training cohort, and similar results were observed in the validation cohort (0.832 (95% CI: 0.760-0.903 vs 0.635 (95% CI: 0.509-0.757), p < 0.001). Furthermore, the prediction accuracy and net benefit of the nomogram verified by the calibration curve, decision curve, NRI, and IDI were satisfactory in the training and validation cohorts. Conclusion: The newly constructed nomogram concluding serum IgA, CRP, and cTNM stage might be helpful in the prognosis prediction for ESCC patients receiving nCRT plus surgery.
RESUMO
Purpose: We aimed to develop a combined predicting model for benign esophageal stenosis (BES) after simultaneous integrated boost (SIB) with concurrent chemotherapy in patients with esophageal squamous cell carcinoma (ESCC). Methods: This study included 65 patients with EC who underwent SIB with chemotherapy. Esophageal stenosis was evaluated using esophagograms and the severity of eating disorders. Risk factors were investigated using univariate and multivariate analyses. Radiomics features were extracted based on contrast-enhanced CT (CE-CT) before treatment. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature selection and radiomics signature construction. The model's performance was evaluated using Harrell's concordance index and receiver operating characteristic curves. Results: The patients were stratified into low- and high-risk groups according to BES after SIB. The area under the curves of the clinical model, Rad-score, and the combined model were 0.751, 0.820 and 0.864, respectively. In the validation cohort, the AUCs of these three models were 0.854, 0.883 and 0.917, respectively. The Hosmer-Lemeshow test showed that there was no deviation from model fitting for the training cohort (p=0.451) and validation cohort (p=0.481). The C-indexes of the nomogram were 0.864 and 0.958 for the training and validation cohort, respectively. The model combined with Rad-score and clinical factors achieved favorable prediction ability. Conclusion: Definitive chemoradiotherapy could alleviate tumor-inducing esophageal stenosis but result in benign stenosis. We constructed and tested a combined predicting model for benign esophageal stenosis after SIB. The nomogram incorporating both radiomics signature and clinical prognostic factors showed favorable predictive accuracy for BES in ESCC patients who received SIB with chemotherapy. Trial registration number and date of registration: Registered in www.Clinicaltrial.gov, ID: NCT01670409, August 12, 2012.