Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Serum IGFBP-1 as a promising diagnostic and prognostic biomarker for colorectal cancer.

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.

Secreted proteins encoded by super enhancer-driven genes could be promising biomarkers for early detection of esophageal squamous cell carcinoma.

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.

A novel nomogram based on clinical blood indicators for prognosis prediction in curatively resected esophagogastric junction adenocarcinoma patients.

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.

Nutritional and immune-related indicators-based Nomogram for predicting overall survival of surgical oral tongue squamous cell carcinoma.

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.

A Nomogram Based on Nutrition-Related Indicators and Computed Tomography Imaging Features for Predicting Preoperative Lymph Node Metastasis in Curatively Resected Esophagogastric Junction Adenocarcinoma.

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.

Serum insulin-like growth factor binding protein 3 as a promising diagnostic and prognostic biomarker in esophagogastric junction adenocarcinoma.

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.

Serum insulin-like growth factor binding protein-3 as a potential biomarker for diagnosis and prognosis of oesophageal squamous cell carcinoma.

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP3) has been reported to be related to the risk of some cancers. Here we focussed on serum IGFBP3 as a possible biomarker of diagnosis and prognosis for oesophageal squamous carcinoma (ESCC). METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum IGFBP3 level in the training cohort including 136 ESCC patients and 119 normal controls and the validation cohort with 55 ESCC patients and 42 normal controls. The receiver operating characteristics curve (ROC) was used to assess the diagnosis value. Cox proportional hazards model was applied to select factors for survival nomogram construction. RESULTS: Serum IGFBP3 levels were significantly lower in early-stage ESCC or ESCC patients than those in normal controls (p < .05). The specificity and sensitivity of serum IGFBP3 for the diagnosis of ESCC were 95.80% and 50.00%, respectively, with the area under the ROC curve (AUC) of 0.788 in the training cohort. Similar results were observed in the validation cohort (88.10%, 38.18%, and 0.710). Importantly, serum IGFBP3 could also differentiate early-stage ESCC from controls (95.80%, 52.54%, 0.777 and 88.10%, 36.36%, 0.695 in training and validation cohorts, respectively). Furthermore, Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic risk factor (HR = 2.599, p = .002). Lower serum IGFBP3 level was correlated with reduced overall survival (p < .05). Nomogram based on serum IGFBP3, TNM stage, and tumour size improved the prognostic prediction of ESCC with a concordance index of 0.715. CONCLUSION: We demonstrated that serum IGFBP3 was a potential biomarker of diagnosis and prognosis for ESCC. Meanwhile, the nomogram might help predict the prognosis of ESCC. Key MessageSerum IGFBP3 showed early diagnostic value in oesophageal squamous cell carcinoma with independent cohort validation. Moreover, serum IGFBP3 was identified as an independent prognostic risk factor, which was used to construct a nomogram with improved prognosis ability in oesophageal squamous cell carcinoma.

Nomogram constructed by immunological and inflammatory indicators for predicting prognosis of patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy plus surgery.

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.

EFNA1 in gastrointestinal cancer: Expression, regulation and clinical significance.

Ephrin-A1 is a protein that in humans is encoded by the EFNA1 gene. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases which play an indispensable role in normal growth and development or in the pathophysiology of various tumors. The role of EFNA1 in tumorigenesis and development is complex and depends on the cell type and microenvironment which in turn affect the expression of EFNA1. This article reviews the expression, prognostic value, regulation and clinical significance of EFNA1 in gastrointestinal tumors.

Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma.

BACKGROUND: Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA). METHODS: Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05). CONCLUSION: Serum DSG2 may be a diagnostic biomarker for ESCC and EJA.

Nomogram based on clinical characteristics and serological inflammation markers to predict overall survival of oral tongue squamous cell carcinoma patient after surgery.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignant disease that is characterized by high rates of metastasis and postoperative recurrence. The aim of this study was to establish a nomogram to predict the outcome of OTSCC patients after surgery. METHODS: We retrospectively analyzed 169 OTSCC patients who underwent treatments in the Cancer Hospital of Shantou University Medical College from 2008 to 2019. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient's overall survival (OS). A nomogram based on these prognostic factors was established and internally validated using a bootstrap resampling method. RESULTS: Multivariate Cox regression analysis revealed the independent prognostic factors for OS were TNM stage, age, lymphocyte-to-monocyte ratio and immunoglobulin G, all of which were identified to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of TNM stage (292.222 vs. 305.480; 298.444 vs. 307.036, respectively), indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected of concordance index (C-index) of nomogram was 0.784 (95% CI 0.708-0.860), which was higher than that of TNM stage (0.685, 95% CI 0.603-0.767, P = 0.017). The results of time-dependent C-index for OS also showed that the nomogram had a better discriminative ability than that of TNM stage. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (P < 0.0001). CONCLUSIONS: The nomogram based on clinical characteristics and serological inflammation markers might be useful for outcome prediction of OTSCC patient.

A Prognostic Model Based on Clinicopathological Features and Inflammation- and Nutrition-Related Indicators Predicts Overall Survival in Surgical Patients With Tongue Squamous Cell Carcinoma.

Objectives: It is reported that inflammation- and nutrition-related indicators have a prognostic impact on multiple cancers. Here we aimed to identify a prognostic nomogram model for prediction of overall survival (OS) in surgical patients with tongue squamous cell carcinoma (TSCC). Methods: The retrospective data of 172 TSCC patients were charted from the Cancer Hospital of Shantou University Medical College between 2008 and 2019. A Cox regression analysis was performed to determine prognostic factors to establish a nomogram and predict OS. The predictive accuracy of the model was analyzed by the calibration curves and the concordance index (C-index). The difference of OS was analyzed by Kaplan-Meier survival analysis. Results: Multivariate analysis showed age, tumor node metastasis (TNM) stage, red blood cell, platelets, and platelet-to-lymphocyte ratio were independent prognostic factors for OS, which were used to build the prognostic nomogram model. The C-index of the model for OS was 0.794 (95% CI = 0.729-0.860), which was higher than that of TNM stage 0.685 (95% CI = 0.605-0.765). In addition, decision curve analysis also showed the nomogram model had improved predictive accuracy and discriminatory performance for OS, compared to the TNM stage. According to the prognostic model risk score, patients in the high-risk subgroup had a lower 5-year OS rate than that in a low-risk subgroup (23% vs 49%, P < .0001). Conclusions: The nomogram model based on clinicopathological features inflammation- and nutrition-related indicators represents a promising tool that might complement the TNM stage in the prognosis of TSCC.

Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor.

BACKGROUND: Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. RESULTS: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). CONCLUSION: The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

A Panel of Tumor-associated Autoantibodies for the Detection of Early-stage Breast Cancer.

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.

Nomogram based on nutritional and inflammatory indicators for survival prediction of small cell carcinoma of the esophagus.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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 P < 0.05). 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). CONCLUSIONS: A nomogram based on nutrition- and inflammation-related indicators was developed to predict the survival of patients with SCCE.

Diagnostic Value of Serum Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) in Colorectal Cancer.

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.

Circulating Levels of L1-cell Adhesion Molecule as a Serum Biomarker for Early Detection of Gastric Cancer and Esophagogastric Junction Adenocarcinoma.

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<0.001). Detection of L1CAM provided a sensitivity of 83.1%, a specificity of 62.2%, and an area under the curve (AUC) of 0.769 (95% CI: 0.715-0.823) in diagnosing GC, and a sensitivity of 66.1%, a specificity of 62.2%, and an AUC of 0.672 (95% CI: 0.590-0.755) in diagnosing EJA. Similar results were observed in the diagnosis of early-stage GC (0.681 (95%CI: 0.596-0.766)) and early-stage EJA (0.674 (95%CI: 0.528-0.820)). Analysis of clinical data showed that the levels of L1CAM were significantly associated with lymph node metastasis in GC (P<0.05). Conclusions: Our study showed that serum L1CAM might be a diagnostic biomarker for GC and EJA.

ApoB/ApoA-1 Ratio as a Novel Prognostic Predictor in Patients With Primary Small Cell Carcinoma of the Esophagus.

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.

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.