Survival Rate Of Gastric Cancer Research Articles

Efficacy of Traditional Chinese Medicine Combined with Chemotherapy in the Treatment of Gastric Cancer: A Meta-analysis.

Objective Meta-analysis was conducted to explore the effects of CM combined with chemotherapy on the effective rate and survival rate of gastric cancer patients. Methods Literature retrieval was performed in PubMed, MEDLINE, Embase, CENTRAL, and CNKI databases. The subject of the literature was to compare the efficacy of CM combined with chemotherapy and chemotherapy alone in patients with gastric cancer. According to the Cochrane manual, the risk of bias was assessed for inclusion in randomized controlled trials. The chi-square test was used for the heterogeneity test. Subgroup analysis and sensitivity analysis were used to explore the causes of heterogeneity. Funnel chart and Egger's test were used to assess publication bias. Results This study included 761 patients with gastric cancer from 10 literatures. The effective rate of chemotherapy in the CM combined group was higher than that in the chemotherapy alone group (odds ratio (OR) = 1.96, 95% confidence interval (CI) (1.39, 2.78), Z = 3.81, P = 0.0001), and there was no heterogeneity among studies (chi2 = 5.68, P = 0.68, I2 = 0%). There was no significant publication bias among all studies (P > 0.05). The one-year survival rate in the CM combined group was higher than that in the chemotherapy alone group (OR = 3.25, 95% CI (1.90, 5.54), Z = 4.32, P < 0.0001). There was no heterogeneity among studies (chi2 = 1.04, P = 0.79, I2 = 0%) and no significant publication bias among studies (P > 0.05). The 3-year survival rate of gastric cancer patients in the traditional Chinese medicine combination group was higher than that in the chemotherapy alone group (OR = 1.71, 95% CI (1.06, 2.78), Z = 2.18, P = 0.03). There was no heterogeneity among studies (chi2 = 2.18, P = 0.54, I2 = 0%), and there was no significant publication bias (P > 0.05). The incidence of nausea and vomiting after chemotherapy in gastric cancer patients in the Chinese medicine combination group was lower than that in the chemotherapy alone group (OR = 0.47, 95% CI (0.34, 0.64), Z = 4.80, P < 0.00001). There was no heterogeneity among studies (chi2 = 8.57, P = 0.48, I2 = 0%), and there was no significant publication bias (P > 0.05). Conclusion CM combined with chemotherapy can improve the effective rate and survival rate of gastric cancer and reduce the incidence of nausea and vomiting after chemotherapy. We recommend a large sample size, multicenter combined randomized controlled trial for validation.

Bioinformatic analysis of cancer-associated fibroblast related gene signature as a predictive model in clinical outcomes and immune characteristics of gastric cancer.

BackgroundGastric cancer (GC) has a high incidence and high mortality rate among Asian countries, and distinguishing predictive prognosis biomarkers for GC are essential. Cancer-associated fibroblasts (CAFs) play a significant role in the progression, immune evasion, and therapeutic resistance of GC. Therefore, CAF-associated genes might have huge potential as prognostic biomarkers for predicting tumor progression and survival rate in GC pateints.MethodsA sum of 1,134 GC patients from the The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE62254, and GSE84437 datasets as well as GC cohorts from Xijing hospital were included. Firstly, we performed univariate Cox regression analysis to identify CAF-associated prognostic genes. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to develop a CAF gene signature (CAFGS) in the TCGA-STAD training cohort. CAFGS’s predictive performance was examined in both the training and validation cohorts, and the relationship between CAFGS and the tumor microenvironment (TME) was investigated by ssGSEA, CIBERSORT, TIMER, and ESTIMATE. Finally, a nomogram of CAFGS was established.ResultsTen CAF-associated genes (ANGPTL4, CPNE8, CST2, HTR1F, IL1RAP, NR1D1, NTAN1, OLFML2B, TMEM259, and VTN) were identified to develop CAFGS. A high CAFGS score represented a worse outcome for GC patients in four cohorts, and a strong correlation was found between CAFGS and the infiltration of immune cells. We showed that CAFs contribute to immune evasion and unfavorable prognoses of GC patients by promoting the formation of an immunosuppressive microenvironment, and a high level of CAF infiltration may attenuate the efficacy of immunotherapy. The nomogram based on CAFGS showed reasonable predictive ability and may deliver great clinical net benefits.ConclusionsWe established a CAFGS model with 10 CAF-associated genes that had a great predictive value for GC prognosis and survival rate evaluation. This study could provide a novel insight for investigating the role of CAFs in GC.

NEAT1 can be a diagnostic biomarker in the breast cancer and gastric cancer patients by targeting XIST, hsa-miR-612, and MTRNR2L8: integrated RNA targetome interaction and experimental expression analysis

BackgroundThe most frequent malignancy in women is breast cancer (BC). Gastric cancer (GC) is also the leading cause of cancer-related mortality. Long non-coding RNAs (lncRNAs) are thought to be important neurotic regulators in malignant tumors. In this study, we aimed to evaluate the expression level of NEAT1 and the interaction of this non-coding RNA with correlated microRNAs, lncRNAs, and mRNAs or protein coding genes, experimentally and bioinformatically.MethodsFor the bioinformatics analyses, we performed RNA-RNA and protein–protein interaction analyses, using ENCORI and STRING. The expression analyses were performed by five tools: Microarray data analysis, TCGA data analysis (RNA-seq, R Studio), GEPIA2, ENCORI, and real-time PCR experiment. qRT-PCR experiment was performed on 50 GC samples and 50 BC samples, compared to adjacent control tissue.ResultsBased on bioinformatics and experimental analyses, lncRNA NEAT1 have a significant down-regulation in the breast cancer samples with tumor size lower than 2 cm. Also, it has a significant high expression in the gastric cancer patients. Furthermore, NEAT1 have a significant interaction with XIST, hsa-miR-612 and MTRNR2L8. High expression of NEAT1 have a correlation with the lower survival rate of breast cancer samples and higher survival rate of gastric cancer patients.ConclusionThis integrated computational and experimental investigation revealed some new aspects of the lncRNA NEAT1 as a potential prognostic biomarker for the breast cancer and gastric cancer samples. Further investigations about NEA1 and correlated mRNAs, lncRNAs, and microRNAs – specially the mentioned RNAs in this study – can lead the researchers to more clear information about the role of NEAT1 in the breast cancer and gastric cancer.

Prognostic biomarker HAMP and associates with immune infiltration in gastric cancer

BackgroundGastric cancer remains one of the most common malignant tumors and has high morbidity and mortality rates. Hepcidin, as a peptide hormone, plays a vital role in regulating systemic iron homeostasis. Nevertheless, the clinical predictive value of HAMP, especially its correlation with immune cell infiltration in gastric cancer, has not yet been elucidated. MethodsHAMP expression in gastric cancer cells and tissues was assessed using experiments and bioinformatics platforms. Clinical and pathologic information was collected to stratify patients with gastric cancer for comparison. We used Kaplan-Meier and Cox regression methods to explore the association between HAMP expression levels and overall survival. Based on “The Cancer Genome Atlas” datasets, we analyzed whether HAMP expression is associated with immune cell infiltration levels and evaluated the prognostic impact of HAMP on survival of patients with gastric cancer partially through immune cell infiltration. ResultsHAMP mRNA was more highly expressed in gastric cancer cells and tumor tissues than in normal tissues. Moreover, elevated HAMP expression was correlated with poor overall survival. In addition, HAMP expression was related to sex, tumor stage, node stage, metastasis stage, Lauren classification, and differentiation in stratified patients. Notably, HAMP gene expression was found to be significantly related to the infiltration levels of immune cells, and that HAMP affects the survival rate in gastric cancer through the immune pathway. ConclusionHigh HAMP expression may serve as an independent prognostic biomarker through the immune pathway in patients with gastric cancer.

Prophylactic hyperthermic intraperitoneal chemotherapy may benefit the long-term survival of patients after radical gastric cancer surgery

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.

Gastric cancer: lessons learned from high-incidence geographic regions.

Gastric cancer is a global health concern. There is a marked geographical variability in the incidence of gastric cancer, with higher incidence in East and Central Asia followed by Latin America and Eastern Europe. Survival rates in gastric cancer are low and strongly stage dependent. Due to the limited survival benefit achieved from currently available therapeutic options, prevention and early diagnosis are essential to minimize morbidity and mortality from this disease. Countries with high incidence of gastric cancer have pioneered the development and implementation of prevention and screening programs. Helicobacter pylori (H. pylori) eradication and dietary modifications are the main preventive strategies. Upper gastrointestinal (UGI) endoscopy is the mainstay screening strategy for early diagnosis. In this article, we review the lessons learned for gastric cancer diagnosis and treatment from high-incidence areas and discuss their applicability for treatment in the Western world to reduce morbidity and mortality from this disease.

Increased Expression of PDK4 Was Displayed in Gastric Cancer and Exhibited an Association With Glucose Metabolism.

Previous studies reported that pyruvate dehydrogenase kinase 4 (PDK4) is closely related to diabetes, heart disease, and carcinomas. Nevertheless, the role of PDK4 in gastric cancer (GC) occurrence and development is yet poorly understood. Our experiments were taken to evaluate PDK4’s function in GC. The Cancer Genome Atlas tumor genome map database was employed to validate the levels of PDK family in different grades and stages of GC. The survival ratio of PDK families in GC was detected by the Kaplan–Meier plotter database. The links existing in the expression of PDK family and the level of tumor-infiltrating immune cells were investigated by tumor immunity assessment resource (TIMER). PDK4-associated signal pathways in GC were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway analysis. PDK4 mRNA level in the GC cells was measured by qRT-PCR. Cell counting kit-8 and Transwell assays were separately carried out to evaluate PDK4-induced influence on GC cell proliferation, migration, and invasion. Our data suggested that GC cells highly expressed PDK4, and PDK4 expression presented a significant relation with the staging, grade, and survival rate of GC. PDK4 expression presented a positive correlation with the types of different infiltrating immune cells, comprising B cells, CD4+ T cells, and dendritic cells. Meanwhile, PDK4 expression exhibited a strong association with macrophages. Survival analysis revealed that the expression of PDK4 displayed a relationship with the prognosis of patients. Therefore, PDK4 was liable to be a biomarker for prognosis. Our results further displayed that PDK4 might modulate the glycolysis level in GC cells, and its expression was associated with GC cell proliferation, migration, and invasion. These data may provide insights into designing a new treatment strategy for GC.

Identification and Validation of SNP-Containing Genes With Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis.

BackgroundGastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer.MethodsSNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells.ResultsFrom the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients.ConclusionOur results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.

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

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center.

BackgroundNatural killer (NK) cells are important for the prognosis of multiple cancers, but their prognostic value remains to be evaluated in patients with gastric cancer. Thus, this retrospective study was conducted at a single center to investigate the association between percentage of NK cells in the peripheral blood and prognosis in patients with gastric cancer.Material/MethodsThe data of 180 gastric cancer patients were collected. Univariate and multivariate Cox regression models were applied to screen candidate prognostic factors. A time-dependent receiver operating characteristic curve was employed to evaluate the ability of NK cells as a prognostic marker. Furthermore, we determined the correlation between the NK cells percentage and other parameters and their clinical significance.ResultsPatients with a higher percentage of NK cells survived longer than those with a lower percentage of NK cells. Cox analysis revealed that NK cells could be used as an independent indicator for patients with gastric cancer. The percentage of NK cells was positively correlated with lymphocyte count and albumin, but was negatively correlated with CA125 and neutrophil-lymphocyte ratio. The area under the curve for NK cells in predicting the 5-year survival rate for gastric cancer was 0.792. This increased to 0.830 upon combining NK cells with neutrophil-lymphocyte ratio. Patients at early T, N, and clinical stages possessed a significantly higher percentage of NK cells compared to those at advanced T, N, and clinical stages of gastric cancer.ConclusionsOur results suggest that a higher percentage of NK cells predicts is associated with longer survival of gastric cancer patients and could serve as an independent prognostic biomarker.

Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway.

Background: The long-term survival rate of gastric cancer (GC) patients at advanced stages remains low worldwide. Circular RNAs (circRNAs) a newly studied type of non-coding RNA that play an important role in the pathogenesis and diagnosis of various diseases. In this research, we aimed to explore the functions of hsa_circRNA_101996 in GC cells and an animal model of GC.Methods: The expression of hsa_circRNA_101996, microRNA (miR)-143, and ten-eleven translocation (TET)-2 in GC tissues, the adjacent tissues, and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Transwell assays were used to analyze the knockdown effects of hsa_circRNA_101996, miR-143, and overexpression of TET2 on cell proliferation, migration, and invasion abilities. Western blotting was used to analyze the expression of matrix metalloproteinases (MMP)2/MMP9. Binding interactions between, hsa_circRNA_101996 and miR-143 and between, miR-143 and TET2 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in Bl6/Rag2/GammaC double knockout mice.Results: The result showed that hsa_circRNA_101996 expression was significantly upregulated in GC tissues compared to that in the adjacent tissues, and its level in cancer tissue was correlated with tumor size, lymphatic metastasis, and distant metastasis. Compared with the low hsa_circRNA_101996 expression group, the three-year survival rate of patients in the high hsa_circRNA_101996 expression group was significantly lower. The knockdown of hsa_circRNA_101996 dramatically suppressed the cell migration, invasion, and proliferation of GC cells by sponging to absorb miR-143 and elevated the expression of TET2. In vivo studies showed that the knockdown of hsa_circRNA_101996 delayed tumor growth. Furthermore, we revealed that TET2 regulates MMP2/MMP9 expression through the DNA demethylation pathway.Conclusion: Our findings indicate that hsa_circRNA_101996 promotes GC development by upregulating MMP2/MMP9 through miR-143/TET2 pathway, which may provide a novel target for GC.

Is Prophylactic Hyperthermic Intraperitoneal Chemotherapy Beneficial to the Long-Term Survival of Patients After Radical Gastric Cancer Surgery: A Systematic Review and Meta-Analysis

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylacticHIPEC after radical gastric cancer surgery in this study. Methods: Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinicalkey databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The primary outcome of this review is the overall survival at 3 years follow-up. The secondary outcomes are the overall survival at 1- and 5-years follow-up, recurrence rate, complications and deaths due to recurrence after surgery. The PROSERO registration number is CRD42021262016. Findings: This meta-analysis included 19 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-,3- and 5-year overall survival rate was significantly favorable to HIPEC (OR=5.10,2.47,1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIEPC group were significantly lower (OR=0.43,0.26 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR=2.44,6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR=0.81,1.19,0.37 respectively). Interpretation: 1-,3-and 5-year overall survival follow-up can be incremented by the prophylactic HIPEC, and which can significantly reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC can cause significant pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery. Funding: None to declare. Declaration of Interest: None to declare.

Infiltrating Immune Cells in Gastric Cancer: A Novel Predicting Model for Prognosis.

Objective: Immune cells infiltrating has been proved to be associated with prognosis in gastric cancer (GC) by studies. This study aims to explore the prognosis value of infiltrating immune cells in gastric cancer.Methods: In our study, the CIBERSORT algorithm was used to calculate the fraction of 22 tumor-infiltrating immune cells (TIIC) in 100 normal and 300 tumor samples from the GEO cohort and 30 normal and 344 tumor samples from the TCGA cohort. Univariate and multivariate Cox regression were used to construct an immune risk score model. Multivariate cox regression was also used to validate whether our risk score model could predict prognosis in GC independently. Furthermore, the model was validated in different patient subgroups to test its independence. P<0.05 was considered statistically significant.Results: The results showed that the fraction of 3 immune cells increased in tumor tissues compared with normal tissues in both the GEO and TCGA cohort. Univariate cox regression analysis showed four cells significantly correlated with survival rate in GC (P<0.05). The immune risk score model was constructed based on the four cells through multivariate cox regression and further validated. The KM survival curve suggested that patients with high risk had poor prognosis than patients with low risk (P<0.05). ROC curve indicated the model was reliable (AUC= 0.67 in the GEO cohort, AUC = 0.65 in the TCGA cohort). Furthermore, multivariate Cox regression showed the model was an independent factor for overall survival predicting in GC (hazard ratio (HR) = 2.35, 95% confidence interval (CI) = 1.63~3.40 in the GEO cohort, HR = 2.87, 95% CI = 1.94~4.25 in the TCGA cohort). Finally, we validated the model in patient subgroups by the KM survival curve.Conclusion: In summary, tumor-infiltrating immune cells play an essential role in GC progression and affect the outcome of GC patients. The immune risk score can predict overall survival for GC independently, and high immune risk score is associated with poor prognosis.

Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes.

With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

High expression of bone morphogenetic protein 1 (BMP1) is associated with a poor survival rate in human gastric cancer, a dataset approaches

Bone morphogenetic protein 1 (BMP1) is a secreted metalloprotease of the astacin M12A family of bone morphogenetic proteins (BMPs). BMP1 activates transforming growth factor-β (TGF-β) and BMP signaling pathways by proteolytic cleavage, which has dual roles in gastrointestinal tumor development and progression.TGF-β promotes invasion and metastasis of gastric cancer (GC) by the help of BMP1, so upregulation of the BMP1 may increase cancer invasiveness in GC. In this study,the transcriptional expression, mutations, survival rate, TFs, miRNAs, gene ontology, and signaling pathways of BMP1 were analyzed by using different web servers. We found higher transcriptional and clinicopathological characteristics expression compared to normal tissues, worsening survival rate in GC. We detected 25 missenses, 15 truncating mutations, 23 TFs, and 8 miRNAs. Finally, we identified and analyzed the co-expressed genes and found that the leukemia inhibitory factor is the most positively correlated gene. The gene ontological features and signaling pathways involved in GC development were evaluated as well. We believe that this study will provide a basis for BMP1 to be a significant biomarker for human GC prognosis.

Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan.

Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population. From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model. Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%). This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.

Expression and clinical significance of paired- related homeobox 1 and Smad2 in gastric cancer.

China has a high incidence rate and low survival rate of gastric cancer. Therefore, there is a great need to further identify novel oncogenes and clinically applicable molecular targets for the diagnosis and treatment of this disease. Expressions of PRRX1, Smad2, epithelial phenotype marker E-cadherin, and interstitial phenotype vimentin protein in a sample of 64 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationship and correlations with clinicopathological features were analyzed. The positive rates of PRRX1, Smad2, E-cadherin, and vimentin protein in primary tumors were 60.94% (39/64), 59.38% (38/64), 34.38%(22/64), and 64.06% (41/64), respectively. A significant correlation was found among the expression of PRRX1, Smad2, E-cadherin, and vimentin (P < 0.05). Expression of the PRRX1, Smad2, and vimentin protein in gastric cancer tissue was correlated with Borrmann classification, lymph node-positive number, the degree of differentiation, depth of tumor invasion, and serum pepsinogen I (PGI) level (P < 0.05), but not with age, sex, serum carcinoembryonic antigen, serum CA199, or PGI/PGII (P > 0.05). The positive rate of PRRX1 protein expression was positively correlated with the protein expression of Smad2 and vimentin, but negatively correlated with E-cadherin protein. PRRX1, Smad2, and vimentin proteins are associated with Borrmann type, lymph node positives, histologic grade, depth of tumor invasion, and serum PGI levels, all of which contribute to a poor prognosis for patients with gastric cancer.

ARPP-19 Mediates Herceptin Resistance via Regulation of CD44 in Gastric Cancer.

PurposeAs the first-line drug for treatment of HER2-positive metastatic gastric cancer (GC), Herceptin exhibits significant therapeutic efficacy. However, acquired resistance of Herceptin limits the therapeutic benefit of gastric cancer patients, in which the molecular mechanisms remain to be further determined.MethodsQuantitative real-time polymerase chain reaction was performed to detect the mRNA levels of ARPP-19 and CD44 in GC cells. Protein levels were determined using Western blot and IHC staining. MTT and soft agar colony formation assays were used to measure cell proliferation. Xenograft model was established to verify the functional role of ARPP-19 in Herceptin resistance in vivo. Sphere formation assay was conducted to determine cell stemness.ResultsWe observed ARPP-19 was up-regulated in Herceptin resistance gastric cancer cells NCI-N87-HR and MKN45-HR. The forced expression of ARPP-19 promoted, whereas the silencing of ARPP-19 impaired Herceptin resistance of HER2-positive gastric cancer cells both in vitro and in vivo. Moreover, ARPP-19 significantly enhanced the sphere formation capacity and CD44 expression, CD44 was also a positive factor of Herceptin resistance in HER2-positive gastric cancer cells. In addition, high level of ARPP-19 was positively associated with Herceptin resistance and poor survival rate of gastric cancer patients.ConclusionWe have demonstrated that ARPP-19 promoted Herceptin resistance of gastric cancer via up-regulation of CD44, our study suggested that ARPP-19 could be a potential diagnostic and therapeutic candidate for HER2-positive gastric cancer.

Abstract C054: Gastric cancer survival among Puerto Rican Hispanics: A ten-year population-based analysis

Abstract Background: Gastric cancer (GC) is one of the top five diagnosed malignancies among U.S. Hispanics. In Puerto Rico during 2011-2015, GC was the 10th and 11th most diagnosed cancer among Puerto Rican Hispanic men and women, respectively. During the same period, GC was the 6th leading cause of cancer death in men and the 8th in women. Although the incidence of GC has decreased during the last two decades in all US racial/ethnic groups, the mortality associated with GC continues to be high and disproportionately affects Hispanics. The aim of this study was to determine and compare the overall five-year relative survival of Puerto Rican Hispanics (PRH) with GC during a ten-year period (2001-2005 and 2006-2010) to that of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Hispanics living in the US. Methods: Data were obtained from the Puerto Rico Central Cancer Registry. Primary cases with diagnostic confirmation of GC, malignancies arising primarily from the gastroesophageal junction to the pylorus, ICD-O-3 codes C16.0 to C16.9 with histologic confirmation (using ICD-O-3 codes) reported during the period of January 1, 2001 to December 31, 2010 were included in the survival analysis. Five-year relative survival rates were calculated using the incidence case files. Analyses were performed using Stata 13.0 and SEER*Stat Software version 8.3.5. Results: For the periods of 2001-2005,2006-2010, and 2011-2015, the age-adjusted incidence rate for GC was 10.5 per 100,000 (n =1,893), 8.8 per 100,000 (n = 1,775), and 8.2 per 100,000 (n = 1,819), respectively. The overall five-year relative survival for 2001-2005 was 27.5% and 32.7% for 2006-2010. For the same study periods, when comparing overall adjusted 5-year relative survival among PRH to that of U.S. racial/ethnic groups, PRH had the lowest survival rates in localized and regional GC followed by U.S. non-Hispanic Blacks. Conclusion: GC continues to be a common cancer among Hispanics despite the decrease in disease burden among other U.S. racial/ethnic groups. GC survival rates among PRH continue to be very low, and marked differences between racial/ethnic groups are observed in localized and regional gastric tumors, suggesting disparities in access to treatment. Studies evaluating the social, genetic, and/or environmental risk factors for GC are of utmost importance to establish health policy and to modify GC screening algorithms among Hispanic populations. Citation Format: Maria Gonzalez-Pons, Carlos Torres-Cintrón, Marievelisse Soto-Salgado, Douglas Morgan, Marcia Cruz-Correa. Gastric cancer survival among Puerto Rican Hispanics: A ten-year population-based analysis [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C054.