Benign Gastric Disease Research Articles

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients.

The albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown. We retrospectively reviewed 227 resectable GC patients in our center. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS prediction. The AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ2 for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system. The AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.

Application of serum pepsinogen and carbohydrate antigen 72-4 (CA72-4) combined with gastrin-17 (G-17) detection in the screening, diagnosis, and evaluation of early gastric cancer

Gastric cancer is a common malignant tumor. The aim of the present study was to analyze the application value of serum pepsinogen (PG), carbohydrate antigen 72-4 (CA72-4), and gastrin-17 (G-17) detection in the screening, diagnosis, and evaluation of early gastric cancer. In total, 122 patients with gastric cancer treated in our hospital from January 2018 to January 2021 were selected as the gastric cancer group and subdivided into the early gastric cancer (group A) and advanced gastric cancer (group B) groups. Sixty-five patients with benign gastric disease treated in the same hospital during the same period were selected as the control group, and 122 healthy people who underwent physical examination during the same period were allocated to the control group. The differences in the levels of G-17, PGI, PGII, PGI/PGII, and CA72-4 were compared; receiver-operating characteristic curves were drawn; and the efficacy of different factors in the diagnosis of early gastric cancer was calculated. G-17, PGI, and PGI/PGII levels in the gastric cancer group were significantly lower than those in the healthy group, and CA72-4 was significantly higher than that in the healthy group (P<0.05), but there was no significant difference in PGII between the 2 groups (P>0.05). G-17, PGI, and PGI/PGII levels in groups A and B were significantly lower than those in the control group. CA72-4 in groups A and B was significantly higher than that of the control group, and was highest in group B (P<0.05). The areas under the curve (AUC) of G-17, PGI, PGI/PGII, and CA72-4 were 0.671, 0.726, 0.769, and 0.602, respectively, and the AUC of combined detection was 0.883, which was significantly higher than that of single detection. Serum PG, CA72-4 combined with G-17 detection has high sensitivity and specificity in the screening and diagnosis of early gastric cancer, and has high clinical application value.

Development of a New Combination Platform for the Early Screening of Gastric Cancer Using Serum Biomarkers

Objective: The combination of pepsinogens (PG I/II) and gastrin-17 (G17) has been used to screen GC in many countries, without satisfactory levels of sensitivity or specificity. The aim of this study was to find a better marker and a new modality in screening early GC. Methods: We measured the serum levels of PG I/II, G17, and prealbumin (PA) from the serum of 481 healthy individuals, 407 benign gastric diseases (BGD), and 416 GC patients using a latex particle-enhanced turbidimetric immunoassay and Sandwich ELISA. Logistic regression analysis was used to obtain the sensitivity and specificity of the combined detection model. Results: When PA was combined with the other biomarkers, the sensitivity and specificity were significantly improved in the ROC curve. The combination of PA+G17+PGI+PGR was the best diagnostic combination for both early and late GC. The AUC, sensitivity, and specificity of the combination for discriminating between early GC and healthy individuals were 0.796, 72.1% and 74.2% respectively. For distinguishing patients with early GC from BGD, the AUC, sensitivity and specificity of the combination were 0.696, 66.7% and 65.4%, respectively. The combination of PA+G17+PGI+PGR improved both the sensitivity and the specificity of GC diagnosis compared with those of the traditional combination of G17+PGI+ PGII +PGR. Conclusion: PA is a valuable indicator for GC and interacts synergistically with PG and G17 in screening for early GC. The new combination platform PA+G17+PGI+PGR may be a potential way for the early screening of GC.

Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer.

Autoantibodies against tumor-associated antigens (TAAbs) can be used as potential biomarkers in the detection of cancer. Our study aims to identify novel TAAbs for gastric cancer (GC) based on human proteomic chips and construct a diagnostic model to distinguish GC from healthy controls (HCs) based on serum TAAbs. The human proteomic chips were used to screen the candidate TAAbs. Enzyme-linked immunosorbent assay (ELISA) was used to verify and validate the titer of the candidate TAAbs in the verification cohort (80 GC cases and 80 HCs) and validation cohort (192 GC cases, 128 benign gastric disease cases, and 192 HCs), respectively. Then, the diagnostic model was established by Logistic regression analysis based on OD values of candidate autoantibodies with diagnostic value. Eleven candidate TAAbs were identified, including autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, RRAS2, RGS4, RHOG, SRARP, RAC1, and TMEM243 by proteomic chips. The titer of autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, and RRAS2 were significantly higher in GC cases while the titer of autoantibodies against RGS4, RHOG, SRARP, RAC1, and TMEM243 showed no difference in the verification group. Next, six potential TAAbs were validated in the validation cohort. The titer of autoantibodies against F8, NRAS, MFGE8, RRAS2, and PTP4A1 was significantly higher in GC cases. Finally, an optimal prediction model with four TAAbs (anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2) showed an optimal diagnostic performance of GC with AUC of 0.87 in the training group and 0.83 in the testing group. The proteomic chip approach is a feasible method to identify TAAbs for the detection of cancer. Moreover, the panel consisting of anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2 may be useful to distinguish GC cases from HCs.

The Role of Cholinesterase in Differential Diagnosis between Gastric Cancer and Benign Gastric Diseases.

Gastric cancer is the fifth most common malignancy worldwide. In early stages, no obvious symptoms are usually observed in gastric cancer patients, and it is especially hard to distinguish gastric cancer from benign gastric diseases, resulting in delayed diagnosis and poor prognosis. Common biomarkers of gastric cancer, such as CEA and CA19-9, are also elevated in benign diseases. There is an urgent need to develop a convenient and reliable biomarker for differentiating between gastric cancer and benign gastric diseases. This study retrospectively analyzed the data of 126 patients, including 73 gastric cancer patients and 53 benign gastric disease patients. Patient characteristics collected for analysis included age, gender, laboratory data, and clinical staging. Unpaired t-test was used to check the difference of cholinesterase level between the gastric cancer group and the benign gastric disease group. Kruskal Wallis H test and Mann-Whitney U test were used to check the difference of cholinesterase level among different stage groups. Receiver operating characteristic (ROC) curve was used to assess whether cholinesterase level can be used as a biomarker for differentiating between gastric cancer and benign gastric diseases. Serum cholinesterase level was decreased significantly in the gastric cancer group in comparison to that of the benign gastric disease group (p < 0.001). In addition, cholinesterase level of stage IV patients was significantly lower than stage I patients. ROC curve analysis revealed that with a cutoff of 5,969.00 U/L, cholinesterase level showed an area under the curve of 0.819 (95% CI 0.732 - 0.905, p < 0.001) in differentiating between gastric cancer and benign gastric diseases. No significant difference in the levels of CEA and CA19-9 was observed between gastric cancer patients and benign gastric disease patients. This study indicated that serum cholinesterase level could be considered as a potential biomarker for differentiating between gastric cancer and benign gastric diseases.

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

OBJECTIVES:Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC.METHODS:Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS:Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC.CONCLUSIONS:Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Application of machine learning in the diagnosis of gastric cancer based on noninvasive characteristics.

BackgroundThe diagnosis of gastric cancer mainly relies on endoscopy, which is invasive and costly. The aim of this study is to develop a predictive model for the diagnosis of gastric cancer based on noninvasive characteristics.AimsTo construct a predictive model for the diagnosis of gastric cancer with high accuracy based on noninvasive characteristics.MethodsA retrospective study of 709 patients at Zhejiang Provincial People's Hospital was conducted. Variables of age, gender, blood cell count, liver function, kidney function, blood lipids, tumor markers and pathological results were analyzed. We used gradient boosting decision tree (GBDT), a type of machine learning method, to construct a predictive model for the diagnosis of gastric cancer and evaluate the accuracy of the model.ResultsOf the 709 patients, 398 were diagnosed with gastric cancer; 311 were health people or diagnosed with benign gastric disease. Multivariate analysis showed that gender, age, neutrophil lymphocyte ratio, hemoglobin, albumin, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were independent characteristics associated with gastric cancer. We constructed a predictive model using GBDT, and the area under the receiver operating characteristic curve (AUC) of the model was 91%. For the test dataset, sensitivity was 87.0% and specificity 84.1% at the optimal threshold value of 0.56. The overall accuracy was 83.0%. Positive and negative predictive values were 83.0% and 87.8%, respectively.ConclusionWe construct a predictive model to diagnose gastric cancer with high sensitivity and specificity. The model is noninvasive and may reduce the medical cost.

Circulating methylated Septin 9 and ring finger protein 180 for noninvasive diagnosis of early gastric cancer.

BackgroundGastric cancer (GC) has a poor prognosis due to patients often being diagnosed at an advanced stage, when metastasis has already occurred. To improve the 5-year survival rate and reduce the number of cancer-related deaths in patients with GC, noninvasive methods for early detection need to be developed. This study aimed to evaluate the value of circulating methylated Septin 9 (SEPT9) and ring finger protein 180 (RNF180) for the early diagnosis of GC.MethodsSeventy-four patients with early GC, 99 patients with benign gastric diseases (BGD) (inflammation, polyps, intestinal metaplasia, ulcers, and erosion), and 57 cases with no evidence of disease (NED) were enrolled. Methylated SEPT9 and RNF180 in circulating cell-free DNA in blood samples from each group were detected, and the positivity rates were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), confidence interval (CI), and area under the curve (AUC) were determined for methylated SEPT9 and RNF180 in relation to early GC.ResultsAs a diagnostic target, methylated SEPT9 had a sensitivity of 28.3% (95% CI: 18.5–40.0%), specificity of 94.2% (95% CI: 89.3–97.3%), and AUC value of 0.616 (95% CI: 52.0–71.1%). Methylated RNF180 had a sensitivity of 32.4% (95% CI: 22.0–44.3%), specificity of 89.7% (95% CI: 83.9–94.0%), and AUC value of 0.636 (95% CI: 54.2–73.0%). A combination of the two yielded a sensitivity of 40.5% (95% CI: 29.3–52.6%), specificity of 85.3% (95% CI: 78.7–90.4%), and AUC value of 0.65 (95% CI: 55.7–74.4%).ConclusionsMethylated SEPT9 and RNF180 could be used as diagnostic biomarkers for early gastric cancer (EGC).

Level of N6-Methyladenosine in Peripheral Blood RNA: A Novel Predictive Biomarker for Gastric Cancer.

Dysregulation of N6-methyladenosine (m6A) is associated with various human diseases including cancer. This study aimed to evaluate the level of m6A as a biomarker for gastric cancer (GC) diagnosis. Peripheral blood samples were collected from 100 GC patients, 30 benign gastric disease (BGD) patients, and 75 healthy controls (HCs). Levels of m6A in total RNA and expression of m6A-related proteins were analyzed. The m6A levels in peripheral blood RNA were significantly increased in the GC group compared with those in the BGD or HC groups; moreover, levels increased with the progression and metastasis of GC and decreased in GC patients after surgery. The area under the curve (AUC) for m6A in the GC group was 0.929 (95% CI, 0.88-0.96), which is markedly greater than the AUCs for carcinoembryonic antigen (CEA; 0.694) and carbohydrate antigen 199 (CA199; 0.603). The combination of CEA and CA199 with m6A improved the AUC to 0.955 (95% CI, 0.91-0.98). The expressions of m6A demethylases ALKBH5 and FTO were significantly downregulated in the GC group compared with the HC group. Coculture with GC cells increased the m6A of RNA in promyelocytic (HL-60) and monocytic (THP-1) leukemia cells and nontumorigenic human peripheral blood B lymphocyte cells (PENG-EBV). Furthermore, a xenograft model enhanced the m6A in peripheral blood RNA of mice. Accordingly, expressions of ALKBH5 and FTO were decreased both in vitro and in vivo. Level of m6A in peripheral blood RNA is a promising noninvasive diagnostic biomarker for GC patients.

Increased Progastrin-Releasing Peptide Expression is Associated with Progression in Gastric Cancer Patients.

PurposeThe purpose of this study was to assess the diagnostic and prognostic value of serum progastrin-releasing peptide (ProGRP) in patients with gastric cancer (GC).Materials and MethodsA total of 150 patients with GC (89 males and 61 females) were recruited, including those with stage I (n=28), stage II (n=33), stage III (n=50), and stage IV (n=39) disease; 50 healthy controls and 66 patients with benign gastric diseases were also enrolled. Levels of serum ProGRP, carcinoembryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) were measured in all subjects.ResultsSerum ProGRP levels were significantly higher in GC patients than in controls (p<0.001), and ProGRP was significantly correlated with tumor size, tumor node metastasis stage, differentiation, invasion depth, and lymph node metastasis (p< 0.005). ProGRP levels were significantly decreased after chemotherapy (p<0.001). Receiver operating characteristic curves revealed a sensitivity and specificity for serum ProGRP in GC of 85.9% and 81.2%, respectively. ProGRP levels were positively correlated with CA72-4 and CEA (r=0.792 and 0.688, p<0.05, respectively). Combined detection of ProGRP, CEA, and CA72-4 showed the best diagnostic power for GC.ConclusionProGRP may be useful as a potential biomarker for GC diagnosis and therapy.

The Role of Diffusion-weighted Imaging in Patients with Gastric Wall Thickening

Gastric cancer is the second leading cause of cancer death worldwide. In the benign and malign gastric pathologies, we measured the Apparent Diffusion Coefficient (ADC) value from the thickened section of the stomach wall. We assessed the diagnostic value of ADC and we wanted to see whether this value could be used to diagnose gastric pathologies. This study has a prospective study design. A total of 90 patients, 27 with malign gastric pathologies 63 with benign gastric pathologies with Gastric Wall (GW) thickening in multidector CT, were evaluated by T2 weighted axial MR imaging and Diffusion-Weighted Imaging (DWI). Measurements were made both from the thickened wall and from the normal GW. Also, a new method called GW/spine ADC ratio was performed in image analysis. The value found after ADC measurement from the GW was proportioned to the spinal cord ADC value in the same section. The ADC values measured from the pathological wall in patients with gastric malignancy (1.115 ± 0.156 x10-3 mm2/s) were significantly lower than the healthy wall measurements (1.621 ± 0.292 × 10-3 mm2/s) and benign gastric diseases (1.790± 0.359 x10-3 mm2/s). GW/spine ADC ratio was also lower in gastric malignancy group. ADC measurement in DWI can be used to distinguish between benign and malign gastric pathologies.

Quantitative analysis of COX-2 promoter methylation in gastric carcinoma.

PurposeTo determine the occurrence of COX-2 methylation in gastric carcinoma (GC), the status and level of CpG methylation in the promoter region of cyclooxygenase-2 (COX-2) were analyzed in early and advanced GCs, as well as in normal gastric tissues.MethodsThe extent of promoter methylation of the COX-2 gene was assessed quantitatively using pyrosequencing in 60 early and 60 advanced GCs samples harvested upon gastrectomy, and 40 normal gastric mucosa samples from patients with benign gastric diseases as controls.ResultsThe methylation frequency for the COX-2 gene was significantly higher in early than in advanced GCs (40.0% vs. 20.0%, P < 0.05). A significant difference was found in COX-2 methylation between GCs and normal gastric tissues (30.0% vs. 10.0%, by PS; P < 0.05). COX-2 gene methylation was significantly associated with the depth of invasion (P = 0.003), lymph node metastasis (P = 0.009), distant metastasis (P = 0.036), and TNM staging (P = 0.007). The overall survival of patients with COX-2 methylation was significantly lower than that of patients without COX-2 methylation (P = 0.005).ConclusionThese results demonstrated that COX-2 promoter methylation was significantly higher in tumor tissues, and was an early event for GC, thus, COX-2 gene methylation may be important in the initial development of gastric carcinogenesis. Thus, GCs with methylation in COX-2 may not be good candidates for treatment with COX-2 inhibitors. Furthermore, COX-2 methylation could be a significant prognostic factor predicting a favorable effect on GC patient outcome when downregulated.

Prognostic value of the cancer oncogene Kelch-like 6 in gastric cancer.

Kelch-like 6 (KLHL6) is a cancer oncogene previously associated with specific human cancers, such as chronic lymphocytic leukaemia. Here, the mechanisms of KLHL6 function were explored in gastric cancer (GC) cells, in an in vivo experimental tumour model, and the prognostic value of KLHL6 analysis in GC tissue evaluated in a cohort of patients with GC. Associations between clinicopathological and survival data and KLHL6 expression in GC tissues were analysed. The effects of downregulation of KLHL6 in GC cells was investigated using proliferation, invasion, apoptosis and lymphangiogenesis assays, and analysis of tumour growth in an in vivo experimental model. KLHL6 was upregulated in 43 per cent of GC tissues compared with 5 per cent of paired non-tumour tissues from 84 patients. KLHL6 protein expression in GC tissues was much higher than that in atrophic gastritis, intestinal metaplasia and dysplasia tissues from benign gastric disease samples. KLHL6 expression was positively related to the intestinal Laurén classification in GC tissues. Downregulated expression of KLHL6 in MGC-803 GC cells reduced colony formation, proliferation, viability, migration and invasion, enhanced apoptosis and inhibited the cell cycle in the G1 phase. Downregulated expression of KLHL6 also suppressed tumour growth in mice. Furthermore, downregulated expression of KLHL6 mRNA reduced the expression of nuclear-associated antigen Ki-67, vascular endothelial growth factor C, hepatocyte growth factor and matrix metalloproteinase 2 in vitro, and KLHL6 protein in tumour tissue of mice. Abnormal expression of the KLHL6 oncogene promoted GC progression in vitro and in vivo, and its expression level in tumour tissue was found to be of prognostic value.

Preoperative serum macrophage activated biomarkers soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163), as novel markers for the diagnosis and prognosis of gastric cancer.

Soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163) are macrophage activation markers which have previously been demonstrated to be increased in patients with inflammation, auto-immunity and malignancies. To investigate the clinical diagnostic and prognostic significance of preoperative serum sMR and sCD163, the present study investigated 143 gastric cancer (GC) patients, 66 subjects with benign gastric disease and 59 healthy controls, using an ELISA assay. Preoperative serum levels of sMR and sCD163 ranged from 0.165 to 0.885 µg/ml (median=0.374 µg/ml) and from 0.291 to 1.760 µg/ml (median=0.628 µg/ml) in GC patients, respectively. The expression levels of sMR and sCD163 were elevated compared with all controls (P<0.0001). Receiver operating characteristic analyses suggested that the optimum diagnostic cut-offs for sMR and sCD163 were 0.3405 µg/ml [area under curve (AUC) 0.7284, sensitivity 61.54%, and specificity 73.60%] and 0.6645 µg/ml (AUC 0.7766, sensitivity 53.85%, and specificity 86.40%), respectively. Notably, the measurement of serum sMR and sCD163 levels in conjugation, markedly enhanced the diagnostic accuracy (AUC 0.8490, sensitivity 70.63% and specificity 84.00%). Preoperative serum sMR and sCD163 levels correlated significantly with serum carcinoembryonic antigen, CA199, CA724 and CA125 concentrations in GC patients (P<0.05), however this association was not observed with sMR and CA724. High preoperative serum sMR and sCD163 levels correlated significantly with shorter overall survival (P=0.0041; P<0.0001, respectively) and were demonstrated to act as adverse prognostic factors (P=0.006; P<0.001, respectively). Furthermore, preoperative serum sMR and sCD163 levels correlated positively with the degree of lymphatic and distant metastasis of GC. In conclusion, preoperative serum sMR and sCD163 may be novel diagnostic and prognostic markers for GC and further studies are required in order to elucidate the underlying molecular mechanisms of sMR and CD163 in the development and progression of GC.

Alu-based cell-free DNA: a novel biomarker for screening of gastric cancer.

Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay. The concentration of CFD was quantitated by bDNA-based Alu assay. CEA, CA19-9, C72-4 and CA50 concentrations were determined by ABBOTT ARCHITECT I2000 SR. We found the CFD concentrations have significant differences between GC patients, benign gastric disease (BGD) patients and healthy controls (P < 0.05). CFD were weakly correlated with CEA (r = −0.197, P < 0.05) or CA50 (r = 0.206, P < 0.05), and no correlation with CA19-9 (r = −0.061, P > 0.05) or CA72-4 (r = 0.011, P > 0.05). In addition, CFD concentrations were significantly higher in stage I GC patients than BGD patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05). Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC. Compared with CEA, CA19-9, CA72-4 and CA50, CFD may prove to be a better biomarker for the screening of GC, thus providing a sensitive biomarker for screening and monitoring progression of GC.

Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer.

AimsTo evaluate the clinical significance of multiple serum tumor markers (TMs) in the diagnosis of gastric cancer (GC) and establish an accurate discriminant equation to identify the presence of GC.ResultsThe serum levels of CEA, CA19-9 and CA72-4 were higher in the GC group than in the control group (P < 0.005). The sensitivity of CEA, CA19-9 and CA72-4 in the diagnosis of GC was 20.1–27.6% individually and increased to 48.2% when they were considered in combination. By using the optimal cut-off value, the sensitivity of CEA, CA19-9 and CA72-4 for the diagnosis of GC was improved but remained unsatisfactory. In addition, we developed the equation Y = −2.185 − 0.015 X1 + 0.180 X2 + 1.226 X3 + 1.505 X4 + 2.749 X5 (X1 = Age, X2 = Sex, X3 =CEA, X4 = CA19-9 and X5 = CA72-4) to predict the presence of GC. This has better accuracy and diagnostic efficiency compared to the combination of TMs.MethodsSerum carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9)and cancer antigen 72-4 (CA72-4) levels were measured in a total of 2288 patients with GC and 1869 healthy volunteers or patients with benign gastric diseases. We established a diagnostic equation using a portion of the data (training set), and validate its accuracy using the other portion of the data (testing set).ConclusionsThe diagnostic equation increases the accuracy rate for the diagnosis of GC and will be helpful in the clinic.

Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases

Interest in the pathophysiological role of IgG fragment crystallizable (Fc) N-linked glycosylation arose from changes in humoral immune responses. In this study, circulating disease-specific IgG (DSIgG) derived from serum immunoinflammation-related protein complexes was isolated from 846 serum samples of 443 patients with benign gastric diseases (BGDs) and 403 patients with gastric cancer (GC), and DSIgG glycopeptides attached to IgG Fc region at the site of Asn297 were analyzed using matrix-assisted laser desorption/ionization- Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). A total of 22 glycopeptides were detected. Statistical analysis indicated that DSIgG1 G1S, DSIgG2 G0F, G1, G2F, and G2FS as well as DSIgG2 galactosylation and sialylation are significantly associated with sex in BGD patients and that the age-specific glycoforms and glycosylation features from DSIgG between BGD patients and GC patients have similar change trends. In addition, significant changes in galactosylation, sialylation, and bisecting N-acetylglucosamine (GlcNAc) from DSIgG were also observed between two pathophysiological states. Receiver operating characteristic (ROC) analysis indicated that the G2FN/G1FN (from DSIgG2) ratio has an excellent capability to distinguish female BGD patients from female GC patients over the age range of 20–79 years, with the sensitivity of 82.6%, the specificity of 82.6%, and the area under curve (AUC) of 0.872.

Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer.

To evaluate whether serum Cathepsin S (Cat S) could serve as a biomarker for the diagnosis and prognosis of gastric cancer (GC), Enzyme-linked immuno sorbent assay (ELISA) was used to detect serum Cat S in 496 participants including healthy controls and patients with benign gastric diseases, gastric cancer, esophageal cancer, liver cancer, colorectal cancer, nasopharyngeal cancer and lung cancer. The levels of serum Cat S were significantly increased in cancer patients, especially in GC patients. The qRT-PCR, Western blotting, and immunohistochemical staining revealed the overexpression of Cat S in GC cell lines and tissues. The diagnostic value of serum Cat S for GC patients from controls resulted in an AUC of 0.803 with a sensitivity of 60.7% and a specificity of 90.0%. Moreover, the levels of serum Cat S were associated with GC tumor volume, lymphoid nodal status, metastasis status, and stages. Moreover, the patients with high levels of serum Cat S had a poorer overall survival. Univariate analysis revealed Cat S expression was a prognostic factor. The knockdown of Cat S significantly suppressed the migration and invasion of GC cells. This study suggested serum Cat S may be a potential biomarker for the diagnosis and prognosis of GC.

Diagnostic significance of soluble human leukocyte antigen-G for gastric cancer

Human leukocyte antigen-G (HLA-G) is a novel tumor marker. Increased level of soluble HLA-G (sHLA-G) in various tumor types has been reported. However, the potential diagnostic value of sHLA-G with other tumor markers in gastric cancer (GC) diagnosis is yet to be explored. In this study, plasma level of sHLA-G was measured in 81 GC patients, 53 benign gastric disease patients and 77 normal controls by ELISA. The serum levels of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 19-9 (CA19-9) and cancer antigen 72-4 (CA72-4) were also determined. Data showed that plasma level of sHLA-G in GC was dramatically increased compared with normal controls and benign gastric disease patients (both p<0.001). The AUC for sHLA-G was 0.730 (p<0.001), superior to serum AFP, CEA, CA125, CA19-9 and CA72-4. After evaluating three cut-offs of sHLA-G, we concluded sHLA-G (cut-off at 128U/ml) plus CA125 in two-biomarker panel test and CA125 plus CA199 plus sHLA-G or CA125 plus CA724 plus sHLA-G in three-biomarker panel test were better choices for GC discrimination. Our findings indicated that sHLA-G was a potential biomarker for GC diagnosis and the combination of sHLA-G with CA125, CA19-9 and CA72-4 can improve the clinical screening and diagnosis for GC.

Heterogeneous expression of cholecystokinin and gastrin receptor in stomach and pancreatic cancer: An immunohistochemical study.

Cholecystokinin (CCK) and gastrin (Gs) are a well known trophic factor for the gastrointestinal tract and their trophic effects are shown mainly toward pancreas and stomach, respectively. Though, the exact characterization of CCK and Gs receptors subtype (cholecystokinin type A receptor [CCKAR] and cholecystokinin type B receptor/gastrin receptor [CCKBR/GR]) in stomach cancer (SC) and pancreatic cancer (PC) is still controversial and necessities further validation. CCKAR and CCKBR/GR expression was analyzed by immunohistochemistry in 55 SC, 25 benign gastric diseases (BGDs), 38 PC (including periampullary carcinoma), and 10 normal pancreatic tissue. The results were statistically correlated with the patient's clinical history to observe the prognostic significance if any. CCKAR expression was detected in 18.2% of SC, 20% of BGD, 65.8% of PC, and 30.0% of normal pancreas tissue samples. The CCKBR/GR expression was detected in 58.2% of SC, 48.0% of BGD, 18.4% of PC, and 60.0% of normal pancreas tissue samples. CCKBR/GR expression was significantly high in well and moderately differentiated SC samples as compared to poorly differentiated samples. Our study showed significantly higher expression of CCKAR and down regulation of CCKBR in PC as compared to control while CCKBR/GR was detected in majority of SC samples. Thus, our study suggests that CCK and Gs receptors may have diagnostic and therapeutic implications. However, study need to be validated in significantly bigger sample size and need to be replicated in different cohorts.