Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer

BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis

BACKGROUND For the prognosis of patients with early gastric cancer(EGC),lymph node metastasis(LNM)plays a crucial role.A thorough and precise evaluation of the patient for LNM is now required.AIM To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients.METHODS Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance,Epidemiology,and End Results database were collected and analyzed.Based on a 7:3 ratio,1550 people were categorized into training sets and 667 people were assigned to testing sets,randomly.Based on the factors influencing LNM determined by the training sets,the nomogram was drawn and verified.RESULTS Based on multivariate analysis,age at diagnosis,histology type,grade,T-stage,and size were risk factors of LNM for EGC.Besides,nomogram was drawn to predict the risk of LNM for EGC patients.Among the categorical variables,the effect of grade(well,moderate,and poor)was the most significant prognosis factor.For training sets and testing sets,respectively,area under the receiver-operating characteristic curve of nomograms were 0.751[95%confidence interval(CI):0.721-0.782]and 0.786(95%CI:0.742-0.830).In addition,the calibration curves showed that the prediction model of LNM had good consistency.CONCLUSION Age at diagnosis,histology type,grade,T-stage,and tumor size were independent variables for LNM in EGC.Based on the above risk factors,prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model

BACKGROUND Hepatocellular carcinoma(HCC)is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis.AIM To investigate the independent predictive markers for disease-free survival(DFS)in patients with HCC and establish a trustworthy nomogram.METHODS In this study,445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined.The survival curve was plotted using the Kaplan–Meier method and survival was determined using the log-rank test.To identify the prognostic variables,multivariate Cox regression analyses were carried out.To predict the DFS in patients with HCC,a nomogram was created.C-indices and receiver operator characteristic curves were used to evaluate the nomogram’s performance.Decision curve analysis(DCA)was used to evaluate the clinical application value of the nomogram.RESULTS Longer DFS was observed in patients with the following characteristics:elderly,I–II stage,and no history of hepatitis B.The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis(TNM)stage.Moreover,the DCA curve revealed that the nomogram had good clinical applicability in predicting 3-and 5-year DFS in HCC patients after surgery.CONCLUSION Age,TNM stage,and history of hepatitis B infection were independent factors for DFS in HCC patients,and a novel nomogram for DFS of HCC patients was created and validated.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors.After resection,one of the major problems is its peritoneal dissemination and recurrence.Some free cancer cells may still exist after resection.In addition,the surgery itself may lead to the dissemination of tumor cells.Therefore,it is necessary to remove residual tumor cells.Recently,some researchers found that extensive intraoperative peritoneal lavage(EIPL)plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients.However,few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.AIM To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.METHODS According to the inclusion and exclusion criteria,a total of 150 patients with advanced GC were enrolled in this study.The patients were randomly allocated to two groups.All patients received laparotomy.For the non-EIPL group,peritoneal lavage was washed using no more than 3 L of warm saline.In the EIPL group,patients received 10 L or more of saline(1 L at a time)before the closure of the abdomen.The surviving rate analysis was compared by the Kaplan-Meier method.The prognostic factors were carried out using the Cox appropriate hazard pattern.RESULTS The basic information in the EIPL group and the non-EIPL group had no significant difference.The median follow-up time was 30 mo(range:0-45 mo).The 1-and 3-year overall survival(OS)rates were 71.0%and 26.5%,respectively.The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group(P<0.05).For the OS of patients,the EIPL,Borrmann classification,tumor size,N stage,T stage and vascular invasion were significant indicators.Then multivariate analysis revealed that EIPL,tumor size,vascular invasion,N stage and T stage were independent prognostic factors.The prognosis of the EIPL group was better than the non-EIPL group(P<0.001).The 3-year survival rate of the EIPL group(38.4%)was higher than the non-EIPL group(21.7%).For the recurrence-free survival(RFS)of patients,the risk factor of RFS included EIPL,N stage,vascular invasion,type of surgery,tumor location,Borrmann classification,and tumor size.EIPL and tumor size were independent risk factors.The RFS curve of the EIPL group was better than the non-EIPL group(P=0.004),and the recurrence rate of the EIPL group(24.7%)was lower than the non-EIPL group(46.4%).The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group(P<0.05).CONCLUSION EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess.In addition,the overall survival curve and RFS curve were better in the EIPL group.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers

BACKGROUND Nearly 66%of occurrences of gastric cancer(GC),which has the second-highest death rate of all cancers,arise in developing countries.In several cancers,the predictive significance of inflammatory markers has been established.AIM To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients.METHODS Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited.Prognostic risk variables were screened for Cox analysis.The C index,receiver operator characteristic(ROC)curve,and decision curve analysis were used to evaluate the nomogram.RESULTS Tumor node metastasis stage,carcinoembryonic antigen,systemic immuneinflammation index,and age were identified as independent predictive variables by multivariate analysis.Systemic immune-inflammation index value was superior to that of other inflammatory indicators.The ROC indicated the nomogram had a higher area under the curve than other factors,and its C-index for assessing the validation and training groups of GC patients was extremely reliable.CONCLUSIONWe created a novel nomogram to forecast the prognosis of GC patients following curativegastrectomy based on blood markers and other characteristics. Both surgeons and patients canbenefit significantly from this new scoring system.

Model established based on blood markers predicts overall survival in patients after radical resection of types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction

BACKGROUND In recent years, the incidence of types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction(AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established.AIM To establish a prognostic model for AEG(types II and III) based on routine markers.METHODS A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic(ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis(TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients.RESULTS Multivariate analysis showed that TNM stage(hazard ratio [HR] = 2.286, P = 0.008), neutrophil-tolymphocyte ratio(HR = 2.979, P = 0.001), and body mass index(HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index(0.697),and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model(3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777;5-year: 0.758, 95%CI:0.708-0.807) was larger than that of TNM staging(3-year: 0.630, 95%CI: 0.585-0.684;5-year: 0.665,95%CI: 0.616-0.715).CONCLUSION Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG(types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.