TNM Staging Of Gastric Cancer Research Articles

Biomarkers of lipid metabolism in gastric cancer: a case control study

BackgroundThe aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer.Methods1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected.ResultsSerum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage.ConclusionsThe serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

Expression of CD151 in Gastric Cancer Tissues and Its Clinical Significance

Objective: To explore the expression of CD151 in gastric cancer tissues and its clinical significance. Methods: Immunohistochemistry was employed to detect the expression of CD151 in gastric cancer tissues and adjacent normal tissues.The relationship between CD151 expression and the clinicopathological characteristics of gastric cancer was analyzed. Results: The expression of CD151 in gastric cancer tissues was significantly higher than in adjacent normal tissues (P &lt;0.05). It was associated with the degree of differentiation, depth of invasion, lymph node metastasis, and TNM staging ofgastric cancer. The survival time of patients with high CD151 expression was significantly shorter than that of those withlow expression (P &lt; 0.05). Conclusion: High expression of CD151 in gastric cancer tissues is correlated with the malignantbiological behavior of gastric cancer and can serve as an indicator for evaluating the prognosis of gastric cancer.

Normalization weighted combination scores re-evaluate TNM staging of gastric cancer: a retrospective cohort study based on a multicenter database.

The pathological depth of tumor invasion (pT) and lymph node metastasis (pN) are critical independent prognostic factors for patients with gastric cancer (GC), representing effective methods for evaluating prognosis. In this study, the authors employed a normalization weight combination score to calculate the weight ratio of the pT stage and pN stage. Subsequently, the authors established a novel weighted TN (wTN) staging model based on these T and N weights, evaluating its prognostic capacity. This study utilized a training cohort from A Medical University Cancer Hospital and a validation cohort from the SEER database. Least absolute shrinkage and selection operator (LASSO) and Cox regression were employed to screen clinical characteristics. Multivariate linear regression and cluster analysis calculated the weight ratio of T stage and N stage in the training and validation cohorts, respectively, followed by re-staging. Prognostic value was evaluated using C-index, likelihood ratio, Wald, and Score tests for wTN stage and tumor-node-metastasis (TNM) stage. A nomogram model was developed, and accuracy was assessed using receiver operating characteristic curve (ROC), decision curve analysis (DCA), and restricted cubic spline (RCS) analyses. LASSO was used for initial screening, selecting eight potential features for Cox analysis. Age, tumor size, metastasis lymph nodes (MLNs), and tumor location were confirmed as independent prognostic factors. wTN was calculated in the training and validation cohorts, and nomograms were established with the independent factors. N stage had a higher weight proportion than T stage in both cohorts (0.625/0.375 in training cohort, 0.556/0.444 in validation cohort). wTN outperformed the 8th TNM stage in C-index, likelihood ratio, Wald, and Score tests in the training cohort, with successful validation in the validation cohort. Stratified analysis of distinct pathological types further demonstrates that wTN staging exhibits superior prognostic performance. The wTN staging model based on T stage and N stage weights has a good prognostic value for GC patients. The same conclusion was obtained in different pathological stratification.

Effect of sevoflurane on CD4+CD25+FOXP3+ regulatory T cells in patients with gastric cancer undergoing radical surgery.

In this study, the proportion of CD4+CD25+FOXP3+ regulatory T (Treg) cells in CD4+ T cells in the peripheral blood of gastric cancer patients before anesthesia induction (T1), after surgery (T2) and the first day after surgery (T3) was studied to explore the effect of sevoflurane and propofol anesthesia on the prognosis of gastric cancer patients. Forty patients with advanced gastric cancer were recruited and randomly divided into the sevoflurane group (S group) and the propofol group (T group). Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ Treg cells in CD4+ T cells in the peripheral blood of patients with T1, T2 and T3, respectively. Compared with stage ⅡB, the proportion of CD4+CD25+FOXP3+ Treg cells in T1, T2 and T3 of stage ⅢA and stage ⅢB patients was increased. Compared with the T group, the expression of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of T2 and T3 in the S group was decreased. The results showed that the expression of CD4+CD25+FOXP3+ Treg cells might be related to the TNM stage of gastric cancer and sevoflurane could alleviate the inhibition of postoperative immune function more than propofol. Sevoflurane effectively reduced the expression level of CD4+CD25+FOXP3+ Treg cells in peripheral blood of T2 and T3 of patients with gastric cancer, providing the theoretical basis for the selection of surgical anesthetics for patients with gastric cancer.

Application of deep learning-based CT texture analysis in TNM staging of gastric cancer

ObjectiveTo analyze the application of deep learning computed tomography (CT) texture analysis in TNM staging of gastric cancer. MethodsUse deep learning software networks to select GoogLeNet and AlexNet models that perform well in image classification work to diagnose gastric cancer pathological images. Based on the characteristics of pathological medical images, the GoogLeNet model was optimized to reduce computational costs while ensuring diagnostic accuracy. On this basis, model fusion is proposed, which integrates network models with different structures and depths to learn more image features and obtain more useful pathological information about gastric cancer. ResultsA deep convolutional neural network was used to automatically classify gastric cancer pathological images using AlexNet and GogLeNet models with significant structural differences. It can be seen that the model achieved high diagnostic accuracy, with a sensitivity of 97.60% and a specificity of 99.49%. However, the experimental method relied more on manually selected pathological features of gastric cancer. The AUC values of maximum frequency, skewness, and kurtosis during the venous phase were 0.735, 0.711, and 0.720, respectively (all P < 0.05). ConclusionThe improved model has the characteristics of both network structures and is more targeted at gastric cancer pathological sections, improving the sensitivity of gastric cancer pathological section recognition. Therefore, deep learning for CT texture analysis can effectively evaluate gastric cancer TNM staging and guide clinical treatment for diagnosing gastric cancer, which has a positive significance.

The relationship between rs968697 genetic polymorphism and gastric cancer susceptibility, TNM stage and survival prognosis

Background HMGA2 can promote the development of multiple malignancies. This study aimed to determine whether a putative functional genetic polymorphism (rs968697 T&gt;C) in the HMGA2 gene promoter region was associated with malignancy susceptibility in the Chinese population. Methods The rs968697 genetic polymorphism was genotyped using the SNaPshot method in the case-control study. The odds ratios and 95% confidence intervals were calculated using a logistic regression model. STATA software was used to conduct the meta-analysis. Results The rs968697 genetic polymorphism was associated not only with susceptibility to malignant tumors [CC versus TT: OR = 0.45, 95%CI = 0.28–0.73, p = .001; CC versus (CT + TT): OR = 0.47, 95%CI = 0.29–0.75, p = .003] including gastric cancer (GC), but also with TNM stage and survival prognosis of GC patients. Genotype-tissue expression analysis, luciferase assay and bioinformatics analysis revealed that the rs968697 genetic polymorphism might affect the binding of transcription factors, especially POLR2A, which in turn regulate the expression of HMGA2. Conclusions The current research suggests that the rs968697 genetic polymorphism may be used as a biomarker for malignancy susceptibility and GC prognosis in the Chinese population.

Progress of Imaging Histology in the Diagnosis and TNM Staging of Gastric Cancer

Progress of Imaging Histology in the Diagnosis and TNM Staging of Gastric Cancer

Comparison of Diagnostic Efficacy of [68Ga]Ga-FAPI-04 and [18F]FDG PET/CT for Staging and Restaging of Gastric Cancer.

PurposeThis study aimed to compare the potential diagnostic efficacy of gallium68-fibroblast-activation protein inhibitor ([68Ga]Ga-FAPI-04) and fluorine18-fluorodeoxyglucose ([18F]-FDG) positron emission tomography-computed tomography (PET/CT) for primary tumors, lymph nodes, and distant metastatic lesions of gastric cancer (GC), and to explore the effects of [68Ga]Ga-FAPI-04 and [18F]-FDG on tumor staging and restaging in GC.MethodsThis single-center retrospective study (NCT2100044131) was conducted at the Affiliated Hospital of the Southwest Medical University between June 2020 and December 2021. Images of patients with GC who were pathologically confirmed and underwent contemporaneous [18F]-FDG and [68Ga]Ga-FAPI-04 PET/CT within 1 week were analyzed. The diagnostic efficacy of [68Ga]Ga-FAPI-04 PET/CT and [18F]-FDG PET/CT for TNM staging of GC was compared using McNemar test. The maximum standard uptake value (SUVmax) of each lesion in the two imaging types was compared using the Mann-Whitney U test.ResultsIn total, 25 patients with GC (mean age, 56 ± 12 years) were evaluated. [68Ga]Ga-FAPI-04 PET/CT exhibited higher sensitivity compared to [18F]-FDG PET/CT for detecting primary tumors (18/19 [94.74%] vs. 13/19 [68.42%], χ2 = 6.866, P < 0.01), lymph node metastasis (75/77 [97.40%] vs. 32/77 [41.56%], χ2 = 2.888, P =0.089), and distant metastases (275/283 [97.17%] vs. 122/283 [43.11%], χ2 = 11.858, P < 0.01). [68Ga]Ga-FAPI-04 accumulation was significantly higher than that of [18F]FDG in tumors (median SUVmax, 10.28 vs 3.20; U=59.00, P < 0.01), lymph node metastasis metastases (median SUVmax, 9.20 vs 3.15; U=53.50, P < 0.01), and distant metastases (median SUVmax, 8.00 vs 4.20; U=200.00, P < 0.01). Compared to [18F]-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT resulted in new oncological findings in 14/25 patients and corrected tumor staging or restaging in 7/25 patients.ConclusionOur preliminary results regarding the impact of [68Ga]Ga-FAPI-04 PET/CT on tumor staging highlight the potential of this approach for increasing the accuracy of GC diagnosis, which may facilitate treatment decision-making.

LncRNA LINC02253 activates KRT18/MAPK/ERK pathway by mediating N6-methyladenosine modification of KRT18 mRNA in gastric cancer.

Long non-coding RNAs (lncRNAs) play a crucial role in gastric cancer (GC) progression. And understanding the role of N6-methyladenosine (m6A) in tumorigenesis is an emerging field in cancer research. Here, we identified a novel oncogene, lncRNA LINC02253, in GC. LINC02253 expression was found to be significantly increased in GC. And LINC02253 expression was closely correlated with tumor size, lymph node metastasis and TNM stage of GC. Besides, GC patients with higher LINC02253 expression had worse 5-year overall survival. Additionally, LINC02253 promoted GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, we determined that LINC02253 increased KRT18 expression through enhancing the stability of KRT18 mRNA. Furthermore, LINC02253 increased m6A modification of KRT18 mRNA to stabilize KRT18 mRNA by recruiting m6A writer METTL3. And, rescue experiments revealed that KRT18 mediated the effects of LINC02253 on growth, migration and invasion of GC cells through activating MAPK/ERK signaling pathway. In conclusion, we demonstrates that oncogenic lncRNA LINC02253 positively regulates GC growth and metastasis via increasing METTL3-mediated mRNA stability of KRT18, extending the understanding of GC pathogenesis regulated by lncRNAs.

Clinical study of CT enhanced scan in preoperative TNM staging of advanced gastric cancer and the effect of misdiagnosis rate.

Clinical study of CT enhanced scan in preoperative TNM staging of advanced gastric cancer and the effect of misdiagnosis rate.

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Correlation between the overexpression of epidermal growth factor receptor and pathological features of gastric cancer: a meta-analysis.

BackgroundTo evaluate the overexpression of epidermal growth factor receptor (EGFR) and its correlation with pathological features of gastric cancer, so as to provide a theoretical basis for anti-EGFR targeted therapy.MethodsPubMed, Embase, Web of Science, CNKI, Wanfang were used to retrieve literature on EGFR expression and gastric cancer tissues between January 2009 and March 2020 and Stata 15.0 software was used to analyze. Age, gender, degree of differentiation, depth of invasion, lymph node metastasis, distant metastasis and TNM staging were analyzed with odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 17 articles were included, with 4,424 patients with gastric cancer, of which 1,268 patients with EGFR overexpression. EGFR was related to the infiltration depth (OR =3.26, 95% CI: 1.95–5.44); related to lymph node metastasis (OR =2.10, 95% CI: 1.45–3.04); related to distant metastasis (OR =1.96, 95% CI: 1.41–2.72); related to TNM staging (OR =3.98, 95% CI: 2.09–7.59). However, EGFR overexpression is not concerned with age, gender and differentiation.ConclusionsEGFR overexpression has the predictive value for depth of invasion, lymph node metastasis, TNM staging and distant metastasis of gastric cancer, and may be a predictor of adverse prognosis of gastric cancer. Targeted therapy for EGFR may be considered as one of the means of comprehensive treatment for gastric cancer.

Analysis of clinicopathologic characteristics of gastric cancer patients undergoing gastrectomy based on a single-center gastric cancer database with above 10 000 cases

Objective: The storage of medical data has been digitized in China, but a unified and structured model has not yet been established. The standardized collection, analysis and sorting of tumor clinical data is the foundation of improving the standard of tumor diagnosis and treatment. Therefore, establishing a database platform of gastric cancer (GC) is an urgent need to integrate data resources and improve the level of diagnosis and treatment. The population economics indexes of GC patients in the last 20 years are analyzed in a single-center GC database. The medical records were structured by natural language processing technology. Authors aim to investigate the clinical pathological characteristics, staging and survival of the GC patients with gastrectomy. Method: A retrospective cohort study was carried out. Clinicopatological data of patients receiving surgical treatment from 2000 to 2019 were retrospectively collected. According to the gastric cancer TNM staging guidelines from the Union for International Cancer Control and the American Joint Committee on Cancer (UICC/AJCC) 8th edition, the structured gastric cancer clinicopathological data were re-evaluated and interpreted. The Kaplan-Meier method and the log-rank test were used to compare survival rate among different groups of patients with complete follow-up data of 2010-2016. Results: Clinicopathological data of 13 492 GC patients were enrolled. The ratio of men to women in the whole group was 3.25:1.00, including 10 320 men with average onset age of 59.68 years, which was basically stable in recent 20 years, and 3172 women with average onset age of 55.93 years, which presented a trend of average increasement of 0.17 year per year. The average hospitalization duration for GC patients showed a decreasing trend year by year, which was 13.87 days in 2019. Average hospitalization cost for GC patients was increasing year by year, with a peak of 83 600 CNY in 2017 and 75 400 CNY in 2019. By natural language identification and exclusion criteria screening, a total of 7218 GC patients obtained structured clinicopathological information. Analysis on clinicopathological characteristics of 3626 GC patients in the last 5 years showed that the average diameter of tumor was (4.44±2.61) cm; the average number of harvested lymph node was 24.30±13.29; the proportion of surgical methods were as following: open surgery in 1398 cases (38.55%), laparoscopic surgery in 1856 cases (51.19%) and robotic surgery in 372 cases (10.26%). The postoperative pathological stage was as following: IA in 658 cases (18.15%), IB in 318 cases (8.77%), IIA in 559 cases (15.42%), IIB in 543 (14.98%), III A in 632 (17.43%), III B in 612 cases (16.88%), III C in 276 cases (7.61%), and IV in 28 cases (0.77%). Complete follow-up data of 3431 patients from 2010 to 2016 were presented. The 1-, 3- and 5-year survival rates were 82%, 69% and 60%, respectively for the whole group. The 1-, 3- and 5-year survival rates for patients undergoing laparoscopic surgery were 83%, 70% and 64%, respectively, and for those undergoing open surgery were 81%, 67% and 56%, respectively, and the difference between the two groups was not statistically significant (P=0.109). The 5-year survival rate of GC patients with different AJCC stages was as following: 88% in IA, 77% in IB, 70% in II A, 62% in II B, 44% in III A, 32% in III B, 22% in III C, and 17% in IV. Conclusion: This study provides basic data for the establishment of comprehensive diagnosis and treatment model of multicenter, shedding light on the improvement of comprehensive treatment of GC in China.

JHDM1D-AS1 aggravates the development of gastric cancer through miR-450a-2-3p-PRAF2 axis

AimsTo investigate the molecular function and mechanisms of JHDM1D antisense 1 (JHDM1D-AS1) during gastric cancer (GC) progression. Materials and methodsThe qPCR assay was used to detect the JHDM1D-AS1 and miR-450a-2-3p expression levels in GC tissues and cell lines. Bioinformatics analysis was used for exploring the lncRNA-microRNA-mRNA interaction network. We performed dual-luciferase reporter assay and qPCR assay in order to validate the direct interactions. We explored the JHDM1D-AS1 and miR-450a-2-3p on GC progression by using JHDM1D-AS1 siRNA and miR-450a-2-3p inhibitor; in vitro CCK-8 assay, colony formation assay, and invasion assay were conducted. Further, in vivo animal experiments were performed, and the expression levels of miR-450a-2-3p and PRAF2 in the tumor tissues were detected using qPCR and western blot analysis. Key findingsThe expression levels of JHDM1D-AS1 and miR-450a-2-3p in GC tissues and cell lines were higher and lower as compared to those in the corresponding normal controls, respectively. Moreover, high levels of JHDM1D-AS1 were closely related with metastasis and the GC TNM stage. Functionally, JHDM1D-AS1 depletion caused an obvious reduction in cell proliferation and invasion both in vitro and in vivo, while the addition of miR-450a-2-3p inhibitor could nullify these effects. Mechanically, JHDM1D-AS1 promoted GC progression via the sponging of miR-450a-2-3p in order to increase PRAF2 expression. SignificanceThe present results showed that the increased expression of JHDM1D-AS1 was closely associated with tumor progression of GC. JHDM1D-AS1/miR-450a-2-3p/PRAF2 axis may be a promising target for GC treatment.

The Ratio of ssDNA to dsDNA in Circulating Cell-Free DNA Extract is a Stable Indicator for Diagnosis of Gastric Cancer.

Due to the different mechanisms of cell-free DNA production, the single-stranded DNA to double-stranded DNA ratio in blood maybe different between healthy individuals and gastric cancer (GC) patients. We aimed to explore the potential application of this ratio in GC diagnosis. The plasma cell-free DNA extracts from 118 healthy individuals and 106 GC patients were prepared. The levels of single-stranded DNA or double-stranded DNA in plasma, and the single-stranded DNA to double-stranded DNA ratio on the diagnostic efficiency for GC were assessed with ROC curve. The relationships between this ratio and the clinical characteristics of GC patients were analyzed. The ratios in 63 GC patients before and after surgery were compared. In healthy individuals, the single-stranded DNA to double-stranded DNA ratio was not affected by factors including age, gender and BMI, and subjected to normal distribution (P = 0.1090). GC patients had a lower value of this ratio than healthy individuals (P < 0.0001). Considering this ratio as a GC diagnostic indicator, the area under ROC curve (AUC) was 0.923[95% confidence interval (CI):0.880-0.955]. This ratio in unresectable GC was obviously lower than that in resectable GC (P = 0.0045). There was a rank correlation between this ratio and GC TNM staging (rho = -0.266, P = 0.0058), but it had no correlation with tumor size (r = 0.14, P = 0.145). Additionally, this ratio was not affected by hemolysis and repeated freeze-thaw of blood samples, and was significantly elevated after surgery(P < 0.0001). The single-stranded DNA to double-stranded DNA ratio in plasma is a stable non-invasive indicator for GC diagnosis.

AKNA Is a Potential Prognostic Biomarker in Gastric Cancer and Function as a Tumor Suppressor by Modulating EMT-Related Pathways.

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases' data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.

Optimization of TNM staging and control of pathological quality in gastric cancer

Comprehensive treatment of gastric cancer is mainly based on the pathological staging. The T stage mainly depends on the accurate determination of the depth of the tumor invasion. The accurate T stage should be standardized pathological examination and continuous sectioning. N stage may be influenced by the number of lymph node examined. Insufficient lymph node examined may lead to stage migration. Therefore, standardizing lymph node dissection and lymph node harvest after surgery is important. M stage is mainly to improve the detection rate of peritoneal lavage cytology (CY), identify high risk factors for peritoneal metastasis, and optimize the prediction of peritoneal metastasis molecular markers, as a complementary methods of clinical examination. Currently, the quality of standardized pathological diagnosis of gastric cancer in China still needs to be improved. This article mainly elucidates the related studies and clinical experience of our center on how to do better in the optimization of gastric cancer TNM staging and pathological quality control.

Role of Sp1 expression in gastric cancer: A meta-analysis and bioinformatics analysis.

Sp1 (specificity protein 1) is an important transcription factor that regulates multiple cancer-related genes. A number of published studies have explored the relationship between Sp1 expression and prognosis in gastric cancer. Therefore, a deeper level of understanding is required into the molecular biological mechanism of gastric cancer. Finding new tumor biomarkers for the accurate prediction of occurrence, recurrence and metastasis of gastric cancer are of great significance. The present study uses a systematic meta-analysis and bioinformatics analysis to acquire evidence for a prognosis marker based on Sp1 expression in gastric cancer. A literature search was performed using PubMed and China National Knowledge Infrastructure on 8th June, 2018. A total of 13 studies were included in the meta-analysis. The meta-analysis showed that the expression of Sp1 was significantly higher in gastric cancer tissue, compared with that of normal mucosa [odds ratio (OR), −0.53; 95% CI, −0.62–0.44; P<0.0001] and dysplasia (OR, 0.24; 95% CI, 0.13–0.44; P<0.0001). A positive association was found Sp1 expression and depth of invasion (OR, 0.31; 95% CI, 0.11–0.86), lymph node metastasis (OR, 0.36; 95% CI, 0.22–0.59), TNM staging of gastric cancer (OR, 0.43; 95% CI, 0.24–0.79) and Lauren's classification (OR, 0.83; 95% CI, 0.51–1.36), but not with sex or tumor differentiation (OR, 1.34; 95% CI, 0.95–1.88). According to the Oncomine database, Sp1 mRNA expression is significantly higher in gastric cancer tissues compared with that in normal tissues (P<0.05), including that of intestinal, diffuse and mixed-type gastric carcinomas (P<0.05). Kaplan-Meier plots show that the expression of Sp1 mRNA is negatively associated with overall and progression-free survival rates of patients with gastric cancer, even when stratified according to expression level (P<0.05). The selected prediction parameter is overall survival or progressive-free survival rate. The expression level of Sp1 was divided into high expression group and low expression group according to the best cut off value provided on the Kaplan-Meier plotter. However, Sp1 protein expression is upregulated in gastric cancer tissues compared with normal tissues and is positively associated with depth of invasion and TNM stage of gastric cancer. The high protein expression of Sp1 might make it a good potential marker for the prognosis of patients with gastric cancer.

MiR-126 inhibits the proliferation and invasion of gastric cancer by downregulation of IGF-1R

Objective: To investigate the expression levels and the mechanism of miR-126 and insulin like growth factor 1 receptor (IGF1R) in gastric cancer tissues and cells. Methods: The expression levels of miR-126 and IGF1R in 60 gastric cancer tissues and matched normal gastric tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, respectively. The association of miR-126 expression with clinicopathology and prognosis of gastric cancer patients was further analyzed. CCK-8, soft agar assay, transwell assay were used to analyze the proliferation and invasion capacity of gastric cancer cells, respectively, while the dual luciferase reporter assay was used to determine the direct target of miR-126. Results: The expression of miR-126 was obviously correlated with lymphatic metastasis, distant metastasis and TNM stage of gastric cancer (all P<0.05). Cox multivariate analysis revealed that lymphatic metastasis, TNM stage, miR-126 and IGF-1R expression were independent risk factors for prognosis of gastric cancer patients (all P<0.05). The expression level of miR-126 in gastric cancer tissues was 2.01±0.23 significantly lower than 10.12±2.15 of normal gastric tissues (P<0.05). CCK-8 result showed that the absorbance values of MKN28 and BGC823 cells at 72 hours after transfected with miR-126 mimics were 1.06±0.05 and 1.01±0.09, respectively, significantly lower than 1.55±0.12 and 1.36±0.12 of the control group (all P<0.05). The clone numbers of MKN28 and BGC823 cells transfected with miR-126 mimics formed in the soft agar were 33±9 and 29±8, respectively, significantly lower than 76±13 and 71±11 of the control group (all P<0.05). Transwell assay showed that the invasived number of MKN28 and BGC823 cells transfected by miR-126 mimics was 98±12 and 89±8, respectively, significantly lower than 154±18 and 161±17 of the control group (all P<0.05). Double luciferase assay further clarified that miR-126 the 3'-untranslated region (3'-UTR) of IGF-1R, and inhibited its protein expression. CCK-8 results showed that overexpression of IGF-1R partially reversed the miR-126 induced proliferation inhibition in MKN28 (1.65±0.14 v. s. 0.98±0.11, P=0.003) and BGC823 cells (1.44 ±0.15 v. s. 0.89±0.10; P=0.006). Likewise, overexpression of IGF-1R partially reversed the miR-126-inhibited invasion of MKN28 (176±19 v. s. 101±14, P=0.005) and BGC823 cells (186±21 v. s. 92±9, P=0.002). Moreover, the inhibitory effects of miR-126 on proliferation were aggravated by silencing of IGF-1R in MKN28 (0.67±0.09 v. s. 0.99±0.12, P=0.021) and BGC823 cells (0.57±0.07 v. s. 0.92±0.12, P=0.012). Conclusion: miR-126 suppresses the proliferation and invasion of gastric cancer cells through targeting the 3'-UTR of IGF-1R and inhibiting its expression.