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Background/Aims: Esophagogastric junction adenocarcinoma (EJA) is a malignant tumor associated with high morbidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages. This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA. Methods: A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Kaplan-Meier survival analysis was carried out to assess the effect of IGFBP7 on overall survival (OS). Results: The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p

Purpose High serum insulin-like growth factor binding protein-7 (IGFBP-7) has been found in several malignant tumors. Here, we aimed to assess the diagnostic potential of serum IGFBP7 in patients with colorectal cancer (CRC). Patients and Methods An enzyme-linked immunosorbent assay (ELISA) was performed to detect IGFBP7 level in the serum of 115 CRC patients and 107 healthy controls, and receiver operating characteristics (ROC) was used to evaluate the accuracy of diagnosis. Results The levels of serum IGFBP7 were significantly higher in CRC than those in normal controls (P < 0.001). With optimized cutoff of 2.050 ng/mL, IGFBP7 showed certain diagnostic value with specificity of 93.9%, sensitivity of 64.5% and an area under the curve (AUC) of 0.815 (95% CI: 0.754–0.877) in CRC. In early-stage CRC, IGFBP7 provided an AUC of 0.826 (95% CI: 0.757–0.896), a sensitivity of 64.5%, and a specificity of 95.8%. Furthermore, when compared with carcinoembryonic antigen (CEA), the accuracy of serum IGFBP7 in the diagnosis of CRC and early-stage CRC were significantly improved. Analysis of clinical data shows that there are no significant differences between IGFBP7 and clinical factors. Conclusion Our study suggested that serum IGFBP7 might serve as a potential biomarker for early-stage CRC diagnosis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has poor prognosis mainly due to the difficulty of making early diagnosis. Therefore, novel biomarkers are critically needed. OBJECTIVE: We aimed to investigate the diagnostic value of serum interleukin-8 (IL-8) in ESCC. METHODS: Data mining of TCGA was used to analyze expression level of IL-8 mRNA in esophageal carcinoma. Serum levels of IL-8 were measured in 103 ESCC patients and 86 normal controls by ELISA. Receiver operating characteristic (ROC) curve was used to evaluate its diagnostic accuracy. RESULTS: IL-8 mRNA expression level and serum IL-8 concentration were both statistically higher in patients than normal controls (P< 0.001). ROC curve demonstrated that the optimum diagnostic cut-off for serum IL-8 was 80.082 pg/mL, providing an area under the curve (AUC) of 0.694 (95% CI: 0.620–0.768), with specificity of 86.0% and sensitivity of 42.7%. The AUC for early-stage ESCC was 0.618 (95% CI: 0.499–0.737), with sensitivity of 35.3% and specificity of 86.0%. Kaplan-Meier analysis and the log-rank test indicated that IL-8 may not be a prognostic predictor for ESCC. CONCLUSIONS: Serum IL-8 was highly expressed in ESCC patients and may be a potential marker for early diagnosis of ESCC.

Background: Low serum L1 cell adhesion molecule (L1CAM) has been found in several malignant tumors. Here, we aimed to evaluate the diagnostic potential for serum L1CAM in patients with gastric cancers (GC) and esophagogastric junction adenocarcinoma (EJA). Methods: Enzyme-linked immunosorbent assay (ELISA) was carried out to detect L1CAM level in sera of 148 GC patients, 59 EJA patients and 148 healthy controls. Receiver operating characteristics (ROC) was employed to evaluate diagnostic accuracy. Results: The concentrations of serum L1CAM were significantly lower in GC and EJA than those in healthy controls (P

Esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EGJA) are the two main types of gastrointestinal cancers that pose a huge threat to human health. ESCC remains one of the most common malignant diseases around the world. In contrast to the decreasing prevalence of ESCC, the incidence of EGJA is rising rapidly. Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers. Current approaches for early diagnosis mainly depend on invasive and costly endoscopy. Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients. Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis, making them promising biomarkers for early detection and monitoring of ESCC and EGJA. In this review, we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two predominant histological types of nonmelanoma skin cancer (NMSC), lacking effective early diagnostic markers. In this study, we assessed the diagnostic value of autoantibodies against p53, MMP-7, and Hsp70 in skin SCC and BCC. ELISA was performed to detect levels of autoantibodies in sera from 101 NMSC patients and 102 normal controls, who were recruited from the Cancer Hospital of Shantou University Medical College. A receiver operator characteristic curve was used to evaluate the diagnostic value. The serum levels of autoantibodies against p53, MMP-7, and Hsp70 were higher in NMSCs than those in the normal controls (all P < 0.01 ). The AUC of the three-autoantibody panel was 0.841 (95% CI: 0.788-0.894) with the sensitivity and specificity of 60.40% and 91.20% when differentiating NMSCs from normal controls. Furthermore, measurement of this panel could differentiate early-stage skin cancer patients from normal controls (AUC: 0.851; 95% CI: 0.793-0.908). Data from Oncomine showed that the level of p53 mRNA was elevated in BCC ( P < 0.05 ), and the Hsp70 mRNA was upregulated in SCC ( P < 0.001 ). This serum three-autoantibody panel might function in assisting the early diagnosis of NMSC.

We previously found a panel of autoantibodies against multiple tumor-associated antigens (BMI-1, HSP70, MMP-7, NY-ESO-1, p53 and PRDX6) that might facilitate early detection of esophagogastric junction adenocarcinoma and esophageal squamous cell carcinoma. Here we aimed at assessing the diagnostic performance of these autoantibodies in breast cancer patients. Enzyme-linked immunosorbent assay was applied to detect sera autoantibodies in 123 breast cancer patients and 123 age-matched normal controls. We adopted logistic regression analysis to identify optimized autoantibody biomarkers for diagnosis and receiver-operating characteristics to analyze diagnostic efficiency. Five of six autoantibodies, BMI-1, HSP70, NY-ESO-1, p53 and PRDX6 demonstrated significantly elevated serum levels in breast cancer compared to normal controls. An optimized panel composed of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 showed an area under the curve (AUC) of 0.819 (95% CI 0.766-0.873), 63.4% sensitivity and 90.2% specificity for diagnosing breast cancer. Moreover, this autoantibody panel could differentiate patients with early stage breast cancer from normal controls, with AUC of 0.805 (95% CI 0.743-0.886), 59.6% sensitivity and 90.2% specificity. Our findings indicated that the panel of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 as serum biomarkers have the potential to help detect early stage breast cancer.

Background To establish and validate a multi-parametric prognostic model based on clinical features and serological markers to estimate the overall survival (OS) in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. Methods The prognostic model was established by using Lasso regression analysis in the training cohort. The incremental predictive value of the model compared to traditional TNM staging and clinical treatment for individualized survival was evaluated by the concordance index (C-index), time-dependent ROC (tdROC) curve, and decision curve analysis (DCA). A prognostic model risk score based nomogram for OS was built by combining TNM staging and clinical treatment. Patients were divided into high-risk and low-risk subgroups according to the model risk score. The difference in survival between subgroups was analyzed using Kaplan–Meier survival analysis, and correlations between the prognostic model, TNM staging, and clinical treatment were analysed. Results The C-index of the model for OS is 0.769 in the training cohorts and 0.676 in the validation cohorts, respectively, which is higher than that of TNM staging and clinical treatment. The tdROC curve and DCA show the model have good predictive accuracy and discriminatory power compare to the TNM staging and clinical treatment. The prognostic model risk score based nomogram show some net clinical benefit. According to the model risk score, patients are divided into low-risk and high-risk subgroups. The difference in OS rates is significant in the subgroups. Furthermore, the model show a positive correlation with TNM staging and clinical treatment. Conclusions The prognostic model showed good performance compared to traditional TNM staging and clinical treatment for estimating the OS in NSCLC (HBV+) patients.

The versatility of IGFBP2, as a secreted protein in cancer cells or a cytoplasmic signaling effector, has been extensively investigated in many malignant cancers. Over the last few decades, IGFBP2, a key member of the IGFBP family, has been identified as an important oncogene in multiple human cancers. In addition, a growing number of studies have shown that IGFBP2 is greatly elevated in serum or tissue in patients with malignant tumors and plays an essential role in several key oncogenic processes, such as tumor cellular proliferation, migration, invasion, angiogenesis, epithelial‑to‑mesenchymal transition, and immunoregulation, which are involved in a variety of signal pathways, usually via an IGF‑independent means. Moreover, growing evidence indicates that aberrant overexpression of IGFBP2 may serve as a useful biomarker for the diagnosis and prognosis of patients, as well as act as a potential therapeutic target for the management of clinical treatment in patients with malignant disease. In the present review, we summarize the current points of view that IGFBP2 performs a role in the initiation and progression of various types of cancer by interacting with several key molecules involved in cancer signaling pathways. We also discuss its potential clinical application value as a diagnostic/prognostic biomarker for patients with malignant tumors.

Objective:Colorectal cancer is one of the most important malignant cancer in the world with high incidence and mortality. Some studies have found that the expression of low serum L1 cell adhesion molecule is associated with poor prognosis in some malignancies. It is suggested that L1 cell adhesion molecule is a candidate serum marker for certain tumors. However, the relationship between serum L1 cell adhesion molecule and colorectal cancer, especially about the diagnostic value, is rarely reported. Therefore, this study aimed to evaluate the diagnostic potential of serum L1 cell adhesion molecule in patients with colorectal cancer.Methods:Enzyme-linked immunosorbent assay was carried out to detect L1 cell adhesion molecule level in sera of 229 patients with colorectal cancer and 145 normal controls. Receiver operating characteristic curves were employed to calculate the accuracy of diagnosis.Results:The levels of serum L1 cell adhesion molecule in the colorectal cancer group were significantly lower than that in normal controls ( P < .05). In the normal group, the area under the receiver operating characteristic curve (area under the curve) of all colorectal cancer was 0.781 (95% confidence interval: 0.734-0.828) and early-stage colorectal cancer was 0.764 (95% confidence interval: 0.705-0.823). With optimized cutoff of 17.760 ng/mL, L1 cell adhesion molecule showed certain diagnostic value with specificity of 90.3% and sensitivities of 43.2% and 36.2% in colorectal cancer and early-stage colorectal cancer, respectively. Clinical data analysis showed that the levels of L1 cell adhesion molecule were significantly correlated with gender ( P < .05) and early and late stages ( P < .05). Furthermore, when compared with carcinoembryonic antigen, serum L1 cell adhesion molecule had significantly improved diagnostic accuracy for both colorectal cancer and early-stage colorectal cancer.Conclusions:Our study demonstrated that serum L1 cell adhesion molecule might be served as a potential biomarker for the diagnosis of colorectal cancer.

Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancer in the world and especially in China with high incidence and mortality. The exploration of novel serum biomarkers is required for early detection of ESCC. We investigated the diagnostic value of serum insulin like growth factor binding protein 7 (IGFBP7) in ESCC, evaluating its potential to improve the diagnosis of ESCC. The serum samples of 106 patients with ESCC and 107 normal controls were tested by enzyme-linked immunosorbent assay (ELISA). The levels of IGFBP7 in ESCC group were significantly higher than that in normal controls, compared by the Mann-Whitney U test (P0.05). Thus, we supposed that serum IGFBP7 might be a potential biomarker in the diagnosis of ESCC.

Background and Aim: Primary small cell carcinoma of the esophagus (SCCE) is a rarely aggressive disease characterized by rapid progression, widespread metastasis, and poor prognosis. This study was aimed to evaluate the prognostic significance of serum lipids for overall survival (OS) in SCCE patients. Methods: We retrospectively analyzed SCCE patients in a training cohort (61 patients) and validated them in a validation cohort (27 patients). These cases were collected from Sun Yat-sen University Cancer Center from 2006 to 2017. Univariate and multivariate Cox survival analyses were performed to determine serum lipids as prognostic factors associated with the patient's OS. Time-dependent receiver operating characteristics (ROC) were used to compare predictive power of independent prognostic factors. The predictive accuracy and discriminative ability of the prognostic factors were measured by the concordance index (C-index) and decision curve, and were compared with the TNM stage system. Results: On multivariate analysis of the training cohort, independent factors for survival were gender, BAR (ApoB/ApoA-1) and TNM stage. The area under the curve (AUC) of BAR+TNM stage in the training cohort was higher than that of TNM stage for OS, and similar result was observed in the validation cohort. The c-index of BAR+TNM stage for predicting the OS was 0.655 (95% CI = 0.571–0.740), which was higher than that of TNM stage [0.614 (95% CI = 0.530–0.698)] in the training cohort. In the validation cohort, the C-index of the BAR+TNM stage for predicting OS was also higher than that of the TNM stage [0.688 (95% CI: 0.570~0.806) vs. (0.512; 95% CI: 0.392~0.632)]. In addition, decision curve analysis also showed that the predictive accuracy of BAR+TNM stage for OS was higher than TNM stage both in the training and the validation cohorts. Conclusions: BAR represents a promising prognostic indicator that might complement TNM stage in the prognosis of SCCE, and that warrant further assessment in large SCCE patient cohort.

Background We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. Methods Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. Results We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). Conclusions Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA. Electronic supplementary material The online version of this article (10.1007/s10120-018-0894-y) contains supplementary material, which is available to authorized users.

Autoantibodies against tumor-associated antigens (TAAs) have been found in many kinds of cancers, and might serve as biomarkers for early cancer diagnosis. The present study was carried out to test if there is any relation between autoantibodies against Fascin and esophageal squamous cell carcinoma (ESCC).One hundred and forty-nine patients with ESCC and 98 control subjects were recruited in the study. The levels of circulating autoantibodies against Fascin were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) was used to calculate diagnostic accuracy.The levels of autoantibodies against Fascin in patients with ESCC were significantly higher than in control subjects (P0.001). Measurement of autoantibodies against Fascin provided an area under the curve (AUC) of 0.636, [95% confidence interval (CI): 0.568-0.704] 24.8% sensitivity (95% CI: 18.3%-37.2%) and 99.0% specificity (95% CI: 93.6%-99.9%). Moreover, serum level of autoantibodies against Fascin in early-stage ESCC was significantly higher than that of normal controls (P0.05). The positive rates of autoantibodies against Fascin were correlated with age (P0.05), but not with gender, tumor size, tumor site, histological grade, T stage, N stage or TNM stage (P0.05).Our results suggest that Fascin autoantibody may be a potential biomarker for the early detection of ESCC.

Esophagogastric junction cancer poses a great threat to human beings both in western countries and East Asia, especially in China and Japan, and its incidence has increased during recent decades. The 5-year survival rate of esophagogastric junction cancer is quite poor compared with that of other gastric cancer sites. Until now, the traditional TNM staging system has been widely used in clinical practice for prognosis. However, the TNM system is based on pathology after surgical resection or radiology using CT and MRI, not on blood markers. Evidently, some research has been reported concentrated on the prognostic value of blood-based markers with the character of non-invasive and non-radioactive in EJA. Hematologic, biochemical and coagulation parameters could be obtained from clinical data and utilized to analyze their prognostic values. Tumor-associated antigens, microRNAs and circulating tumor cells have also been reported in EJC prognosis. In this article, we review research focused on blood-based markers to evaluate their prognostic value in esophagogastric junction cancer, especially its main subtype adenocarcinoma.

Background: Early detection would improve upper gastrointestinal cancer prognosis. We aimed to identify serum protein biomarker for the detection of early-stage upper gastrointestinal cancer. Methods: We performed a three-tiered study including 2028 participants from three medical centres. First, we applied two different antibody arrays to screen candidate serum proteins that increased in 20 patients with oesophageal squamous cell carcinoma (ESCC) compared with 20 normal controls. We then evaluated the selected protein by enzyme-linked immunosorbent assay in 1064 participants including 731 upper gastrointestinal cancer patients (287 ESCCs, 237 oesophagogastric junction adenocarcinomas (EJAs), and 207 stomach cancers) and 333 normal controls. The diagnostic value of the selected protein was finally validated in two independent cohorts of ESCC patients and controls (n=472 and 452, respectively). The receiver operating characteristic was used to calculate diagnostic accuracy. Findings: Serum insulin-like growth factor binding protein-1 (IGFBP-1) identified in both antibody arrays showed significantly elevated levels in upper gastrointestinal cancers, compared with normal controls. Serum IGFBP-1 provided high diagnostic accuracy of early-stage ESCC, EJA, stomach and cancer (areas under the curve: 0·898, 0·936 and 0·864, respectively). This protein maintained diagnostic performance for early-stage ESCC in independent cohorts 1 and 2 (0·849 and 0·911, respectively). Additionally, serum levels of IGFBP-1 dropped significantly after surgical resection of primary tumours, compared with the corresponding pre-operative ESCC samples (p < 0·05). Interpretation: Serum IGFBP-1 represents a promising diagnostic biomarker to detect early-stage upper gastrointestinal cancer. Keywords: Upper gastrointestinal cancer, IGFBP-1, Early diagnosis, Sensitivity, Specificity

Small cell carcinoma of the esophagus (SCCE) is a rare type of esophageal cancer, and the parameters for prediction of SCCE outcome are unclear. This study aimed to construct a nomogram to predict the outcome of SCCE.Patients who underwent treatments at the Sun Yat-Sen University Cancer Center were recruited and divided randomly into training and validation cohorts (61 and 32 patients, respectively). A Cox regression analysis was utilized to identify independent prognostic factors to establish a nomogram and predict overall survival (OS) and disease-free survival (DFS).Information on pretreatment nutritional candidate hemoglobin and inflammation-related neutrophil-to-lymphocyte ratio and platelet count were entered into the nomogram. In the training cohort, the concordance index of the nomogram for OS was 0.728, higher than that obtained by tumor/node/metastasis staging (0.614; P = 0.014). A significant difference was observed in the nomogram for DFS (0.668 vs tumor/node/metastasis stage: 0.616; P = 0.014). Similar results were found in the validation group. The decision curve analysis, net reclassification improvement, and integrated discrimination improvement showed moderate improvement of the nomogram in predicting survival. Based on the cut point calculated according to the constructed nomogram, the high-risk group had poorer OS and DFS than the low-risk group in both cohorts (all P0.05). Moreover, the DFS of patients receiving surgery in the high-risk group was better than that of patients receiving single radiation therapy or chemotherapy (P = 0.0111).A nomogram based on nutrition- and inflammation-related indicators was developed to predict the survival of patients with SCCE.

Riboflavin is an essential micronutrient for normal cellular activity, and deficiency may result in disease, such as cancer. We performed a case-control study to explore the association of riboflavin levels with risk and prognosis of esophageal squamous cell carcinoma (ESCC). Plasma riboflavin levels, as measured by enzyme-linked immunosorbent assay (ELISA), in ESCC patients were significantly lower than in those of healthy controls (7.04 ± 6.34 ng/ml vs. 9.32 ± 12.40 ng/ml; P0.05). Moreover, there was an inverse relationship between riboflavin level and risk of ESCC (odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, P = 0.02). The 5-year relapse-free and overall survival rates were significantly lower when riboflavin levels were ≤0.8 ng/ml than0.8 ng/ml (relapse-free survival rate: 29.4% vs. 54.8%; overall survival rate: 28.6% vs. 55.6%). Plasma riboflavin level was an independent protective factor for both relapse-free (hazard ratio (HR) = 0.325, 95% CI = 0.161-0.657, P = 0.002) and overall survival of ESCC patients (HR = 0.382, 95% CI = 0.190-0.768, P = 0.007). In conclusion, plasma riboflavin levels are significantly related to risk and prognosis of ESCC patients, suggesting that moderate supplementation of riboflavin will decrease risk and prevent recurrence of ESCC and also improve prognosis of ESCC patients.

Background: Esophagogastric junction adenocarcinoma (EJA) is one of the most common malignant tumors of digestive tract with high mortality worldwide. Given a lack of early diagnosis biomarkers, the prognosis of EJA is poor. Non-invasive biomarkers for early-stage EJA are urgently required. Objective: We aimed at evaluating the early diagnostic value of serum interleukin-8 (IL-8) level in EJA patients. Methods: The IL-8 mRNA expression data were analyzed based on the stomach cardia adenocarcinoma samples of The Cancer Genome Atlas (TCGA) database. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of serum IL-8 in 95 EJA patients and 95 normal controls enrolled from 2 different cancer hospitals. The diagnostic accuracy of serum IL-8 was evaluated by applying Mann-Whitney U test and receiver operating characteristic (ROC) curve. Results: The mRNA expression levels and serum levels of IL-8 in EJA group were significantly higher than those in the normal group (all P < 0.001). The areas under the ROC curve (AUC) were 0.661 (95% CI, 0.583-0.740) and 0.745 (95% CI, 0.606-0.885), with the sensitivities of 43.2% (95% CI, 33.2%-53.7%) and 66.7% (95% CI, 46.0%-82.8%) and the specificities of 87.4% (95% CI, 78.6%-93.1%) in EJA group and early-EJA group, respectively, when the optimal cutoff value was 109.086 pg/mL. The clinical data analysis showed there were significant correlations between patient genders, depth of invasion, lymph node metastasis, TNM stage and the serum level of IL-8 (all P < 0.05). Conclusions: Serum IL-8 represents a potential diagnostic biomarker to identify early-stage EJA.

Introduction: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the pathophysiology of atherosclerosis and acute coronary syndromes (ACS). Circulating soluble LOX-1 (sLOX-1) has been linked to the risk of coronary artery disease (CAD). Our aim was to test if baseline serum sLOX-1 was associated with major adverse cardiovascular events (MACE) in patients with stable CAD. Materials and methods: This multicentre pilot study enrolled 833 stable CAD patients. All patients were followed for two years. Serum sLOX-1 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). The association between sLOX-1 concentrations and MACE was assessed by logistic regression, Kaplan-Meier survival curves and Cox proportional hazards analyses. Logistic regression analysis was employed to assess the predictors of complex lesion. Results: Multivariate logistic regression analysis revealed that sLOX-1 concentration was an independent predictor of MACE (OR 2.07, 95%CI 1.52 - 2.82; P < 0.001). Kaplan-Meier cumulative survival curves showed that the incidence of MACE in patients with a high sLOX-1 concentration was significantly higher than in patients with an intermediate or low sLOX-1 concentration (P < 0.001). Soluble LOX-1 concentrations were independently correlated with coronary complex lesions (OR 2.32, 95%CI 1.81 - 2.97; P < 0.001). Conclusions: Baseline sLOX-1 concentrations were correlated with 2-year MACE in stable CAD patients. Furthermore, patients with high serum sLOX-1 concentrations had higher cumulative incidence of MACE compared to those with low serum sLOX-1 concentrations.

Background. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) may be a potential biomarker of coronary artery disease (CAD) and stroke. Objective. We aimed to investigate the association and prognostic value of elevated sLOX-1 concentrations with regard to long-term major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with CAD undergoing primary percutaneous coronary intervention (PCI). Methods. A total of 1011 patients were enrolled. Serum sLOX-1 concentrations were detected by the enzyme-linked immunosorbent assay (ELISA). Patients were followed for 2 years. Multivariate Cox regression and Kaplan-Meier survival curve were explored to assess the association between sLOX-1 and MACCEs. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of sLOX-1. Results. Two-year MACCEs were associated with serum sLOX-1 concentrations (HR 1.278, 95% CI 1.019-1.604, P=0.034), left main disease (HR 2.938, 95% CI 1.246-6.925, P=0.014), small-caliber stents used (HR 2.207, 95% CI 1.189-4.095, P=0.012), and total stent length (HR 1.057, 95% CI 1.005-1.112, P=0.030). Serum sLOX-1 concentration≥1.10 ng/ml had maximum sensitivity and specificity in predicting the occurrence of 2-year MACCEs (P<0.001). Patients with higher serum sLOX-1 concentrations showed a significantly higher incidence of MACCEs in the Kaplan-Meier curve (P<0.001). The combination of any of the risk factors identified in multiple Cox regression was associated with a stepwise increase in MACCE rate (P<0.001). Conclusions. High baseline serum sLOX-1 concentration predicts 2-year MACCEs and shows an additional prognostic value to conventional risk factors in patients after primary PCI. sLOX-1 determination might play a complementary role in the risk stratification of patients with CAD treated with PCI.

Background: Early detection would significantly improve cancer prognosis. We aimed to identify serum protein biomarker for early cancer detection and assess the diagnostic value in various types of cancers. Methods: We performed a three-stage study, and recruited participants of normal controls and seven different types of cancer patients (oesophageal squamous cell carcinoma (ESCC), oesophagogastric junction adenocarcinoma (EJA), stomach cancer, colorectal cancer, lung cancer, nasopharyngeal cancer and breast cancer) from two medical centres. We applied two different antibody arrays to screen candidate serum protein which were increased in 20 ESCC patients compared with 20 matched normal controls. In biomarker assessment stage, the diagnostic value of the selected protein measured by ELISA was evaluated in seven cancer types, and was validated in two independent cohorts of ESCC patients and controls (cohorts 1 and 2). Receiver operating characteristics (ROCs) with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to calculate diagnostic accuracy. Findings: We recruited 1628 participants to biomarker assessment stage: 287 with ESCC, 237 with EJA, 207 with stomach cancer, 138 with colorectal cancer, 126 with lung cancer, 150 with nasopharyngeal cancer, 150 with breast cancer and 333 normal controls, and 472 and 452 participants comprised of ESCC patients and controls to the two independent validation cohorts. Serum IGFBP-1 showed elevated level for ESCC in both antibody arrays. A significant increase in the serum IGFBP-1 level on all cancer types except breast cancer was confirmed by ELISA, compared with normal controls. Serum IGFBP-1 provided a high diagnostic accuracy of gastrointestinal tumours (AUC 0·880-0·938, sensitivity 65·22-77·22%, and specificity 90·39%). Similar results were noted for early-stage gastrointestinal tumours (0·858-0·936, 60·29-83·93%, and 90·39%). In two validation cohorts, serum IGFBP-1 maintained diagnostic performance for early stage ESCC (0·849, 68·04%, and 89·09% in cohort 1, and 0·911, 72·34% and 87·37% in cohort 2). Furthermore, when compared with CEA, Cyfra21-1 and SCCA tested alone or together, serum IGFBP-1 had significantly improved diagnostic accuracy for ESCC and early stage ESCC. Interpretation: Serum IGFBP-1 is a potential biomarker with high diagnostic value for the early detection of gastrointestinal cancer. Funding Statement: This work was supported by funding from the Natural Science Foundation of China (31600632, 81772532 and 81872372), the Population-based prospective cohort study of esophageal cancer and precancerous lesions in high risk areas (2016YFC0901404), the National Cohort of Esophageal Cancer of China (2016YFC0901400), and the Guangdong Esophageal Cancer Institute Science and Technology Program (M201713), the Natural Science Foundation of Guangdong Province (2018A030307079) and the Shantou University Medical College Clinical Research Enhancement Initiative (201428). Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by the Institutional Review Boards for Human Research at each hospital, and informed consent was obtained from all participants.

Nasopharyngeal carcinoma (NPC) is prevalent in Southern China and Southeast Asia, and autoantibody signatures may improve early detection of NPC. In this study, serum levels of autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, Prx VI, and Bmi-1) and Epstein–Barr virus capsid antigen-IgA (VCA-IgA) were tested by enzyme-linked immunosorbent assay in a training set (220 NPC patients and 150 controls) and validated in a validation set (90 NPC patients and 68 controls). We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. ROC curves showed that use of these 6 autoantibody assays provided an area under curve (AUC) of 0.855 [95% confidence interval (CI), 0.818–0.892], 68.2% sensitivity, and 90.0% specificity in the training set and an AUC of 0.873 (95% CI, 0.821–0.925), 62.2% sensitivity, and 91.2% specificity in the validation set. Moreover, the autoantibody panel maintained diagnostic accuracy for VCA-IgA–negative NPC patients [0.854 (0.809–0.899), 67.8%, and 90.0% in the training set; 0.879 (0.815–0.942), 67.4%, and 91.2% in the validation set]. Importantly, combination of the autoantibody panel and VCA-IgA improved diagnostic accuracy for NPC versus controls compared with the autoantibody panel alone [0.911 (0.881–0.940), 81.4%, and 90.0% in the training set; 0.919 (0.878–0.959), 78.9%, and 91.2% in the validation set), as well as for early-stage NPC (0.944 (0.894–0.994), 87.9%, and 94.0% in the training set; 0.922 (0.808–1.000), 80.0%, and 92.6% in the validation set]. These results reveal autoantibody signatures in an optimized panel that could improve the identification of VCA-IgA–negative NPC patients, may aid screening and diagnosis of NPC, especially when combined with VCA-IgA. Cancer Prev Res; 8(8); 729–36. ©2015 AACR.

Background Nasopharyngeal carcinoma (NPC) is a major head and neck cancer with high occurrence in Southeast Asia and southern China. We aimed to identify autoantibodies that may contribute to early detection of NPC. Methods We used serological proteome analysis to identify candidate autoantibodies against tumor-associated antigens. Levels of autoantibodies and Epstein–Barr virus capsid antigen-IgA (VCA-IgA) were measured by ELISA in 129 patients with NPC and 100 normal controls. We employed receiver operating characteristics to calculate diagnostic accuracy. Results Sera from patients with NPC yielded multiple spots, two of which were identified as PRDX2 and PRDX3. Levels of serum autoantibodies against PRDX2 and PRDX3 were significantly higher for patients with NPC than for normal controls (P

Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P<0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P<0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

Esophageal squamous cell carcinoma (ESCC) can be treated effectively if diagnosed at an early stage. We evaluated whether measurement of Dickkopf-1 (DKK1) in combination of DKK1 autoantibodies in serum may benefit early diagnosis of ESCC. Serum DKK1 and DKK1 autoantibodies were measured by enzyme-linked immunosorbent assay in a training cohort (185 ESCC samples vs. 97 normal controls) and validated in a validation cohort (104 ESCC samples vs. 53 normal controls). Receiver operating characteristics (ROC) was applied to calculate diagnostic accuracy. The serum levels of DKK1 and DKK1 autoantibody were significantly higher in ESCC patients than in controls, respectively (P Citation Format: Yu-Hui Peng, Yi-Wei Xu, En-Min Li, Li-Yan Xu. Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3980.