Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer.

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.

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.

Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis.

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.

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.

The diagnostic value of serum insulin-like growth factor binding protein 7 in gastric cancer.

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.

Association between IGFBP1 expression and cancer risk: A systematic review and meta-analysis.

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.

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.

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.

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.

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.

Prognostic value of IGFBP2 in various cancers: a systematic review and meta-analysis.

BACKGROUND: The prognostic significance of insulin-like growth factor binding protein 2 (IGFBP2) expression has been explored in plenty of studies in human cancers. Because of the controversial results, the meta-analysis was carried out to evaluate the relevance of IGFBP2 expression with the prognosis in various tumors. METHODS: The data searched from four databases (Pubmed, Embase, Cochrane library, and Web of science) was used to calculate pooled hazard ratios (HRs) in this meta-analysis. Subgroup analyses were stratified by ethnicity, cancer type, publication year, Newcastle-Ottawa Scale score, treatments, and populations. RESULTS: Twenty-one studies containing 5560 patients finally met inclusion criteria. IGFBP2 expression was associated with lower overall survival (HR = 1.57, 95% CI = 1.31-1.88) and progression-free survival (HR = 1.18, 95% CI = 1.04-1.34) in cancer patients, but not with disease-free survival (HR = 1.50, 95% CI = 0.91-2.46) or recurrence-free survival (HR = 1.50, 95% CI = 0.93-2.40). The subgroup analyses indicated IGFBP2 overexpression was significantly correlated with overall survival in Asian patients (HR = 1.42, 95% CI = 1.18-1.72), Caucasian patients (HR = 2.20, 95% CI = 1.31-3.70), glioma (HR = 1.36, 95% CI = 1.03-1.79), and colorectal cancer (HR = 2.52, 95% CI = 1.43-4.44) and surgery subgroups (HR = 1.97, 95% CI = 1.50-2.58). CONCLUSION: The meta-analysis showed that IGFBP2 expression was associated with worse prognosis in several tumors, and may serve as a potential prognostic biomarker in cancer patients.

Rosmarinic Acid Attenuates the Lipopolysaccharide-Provoked Inflammatory Response of Vascular Smooth Muscle Cell via Inhibition of MAPK/NF-κB Cascade.

Rosmarinic acid (RA) is a phenolic compound that has several bioactivities, such as anti-inflammatory and antioxidant activities. Here, we further investigate the anti-inflammatory effect of RA on rat A7r5 aortic smooth muscle cells with exposure to lipopolysaccharide (LPS). Our findings showed that low-dose RA (10-25 µM) did not influence the cell viability and morphology of A7r5 cells and significantly inhibited LPS-induced mRNA expression of the pro-inflammatory mediators TNFα, IL-8, and inducible NO synthase (iNOS). Consistently, RA reduced the production of TNFα, IL-8, and NO by A7r5 cells with exposure to LPS. Signaling cascade analysis showed that LPS induced activation of Erk, JNK, p38 mitogen-activated protein kinase (MAPK), and NF-κB, and RA treatments attenuated the activation of the three MAPKs and NF-κB. Moreover, cotreatment with RA and Erk, JNK, p38 MAPK, or NF-κB inhibitors further downregulated the mRNA expression of TNFα, IL-8, and iNOS, and decreased the production of TNFα, IL-8, and NO by A7r5 cells. Taken together, these findings indicate that RA may ameliorate the LPS-provoked inflammatory response of vascular smooth muscle cells by inhibition of MAPK/NF-κB signaling.

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.

Autoantibodies against p53, MMP-7, and Hsp70 as Potential Biomarkers for Detection of Nonmelanoma Skin Cancers.

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.

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.

IGFBP-1 in cancer: expression, molecular mechanisms, and potential clinical implications.

Insulin-like growth factor binding protein-1 (IGFBP-1) belongs to the insulin-like growth factor (IGF) system, which plays an indispensable role in normal growth and development, and in the pathophysiology of various tumors. IGFBP-1 has been shown to be associated with the risk of various tumors, and has a vital function in regulating tumor behaviors such as proliferation, migration, invasion and adhesion through different molecular mechanisms. The biological actions of IGFBP-1 in cancer are found to be related to its phosphorylation state, and the IGF-dependent and -independent mechanisms. In this review, we provided an overview of IGFBP-1 in normal physiology, and its aberrantly expression and the underlying molecular mechanisms in a range of common tumors, as well as discussed the potential clinical implications of IGFBP-1 as diagnostic or prognostic biomarkers in cancer.

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.