Gastric Cancer Death Research Articles

Short-term and long-term effect of nutrition intervention in the Linxian Dysplasia Nutrition Intervention Trial and the reason for disappearance of the intervention effect: A cohort study.

The objective of this study was to determine the short-term and long-term effects of a nutrition intervention in using 37years of follow-up data. The Linxian Dysplasia Population Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial with 7years of intervention and 30years of follow-up. The Cox proportional hazard model was used for analyses. Subgroup analyses were conducted in age and sex subgroups, and the 30years of follow-up were divided into two 15-year early and late periods. The results at 37years did not indicate any effects on mortality from cancers or other diseases. In the first 15years, the intervention decreased the overall risk of gastric cancer deaths in all participants (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.58-1.00) and in the subgroup participants younger than 55 years (HR, 0.64; 95% CI, 0.43-0.96). In addition, in the group younger than 55 years (HR, 0.58; 95% CI, 0.35-0.96), the intervention decreased the risk of death from other diseases; and, in the group aged 55 years and older (HR, 0.75; 95% CI, 0.58-0.98), the intervention reduced the risk of death from heart disease. There were no significant results in the later 15years, which indicated the disappearance of the intervention effect. Comparing demographic characteristics between those who died during the two periods, the participants who died later included more women, had a higher education level, had a lower smoking rate, were younger, and also more had a mild degree of esophageal dysplasia, representing a better lifestyle and health condition. Long-term follow-up indicated no effect of nutrition on deaths in a population with esophageal squamous dysplasia, further supporting the significance of continuous nutritional intervention for cancer protection. The pattern of protective effect of a nutrition intervention on gastric cancer in patients with esophageal squamous dysplasia was similar to that in the general population. Participants who died in the later period had more protective factors than those who died in the earlier period, contributing to the obvious effect of the intervention in early stage disease.

Biomimetic single-atom nanozyme system for efficient inhibition of gastric cancer ascites via SO2 gas-enhanced nanocatalytic cancer therapy

Peritoneal metastasis is a frequent cause of death in gastric cancer, and it is newer mainly treated by hyperthermic intraperitoneal chemotherapy (HIPEC),whereas the patients experience serious side effects.Thus it is urgent to develop new alternatives, one example being Cu single-atom nanozymes (SAZ) with peroxidase (POD)-like activity and which have good nanocatalytic tumor therapy (NCT) capabilities. A previously described approach was used to produce platelet membrane vesicles (PV) and Cu SAZ. However, insufficient hydrogen peroxide (H2O2) limit NCT effects. Therefore, to overcome these limitations, through physical extrusion, an SO2 prodrug (benzothiazole sulfinate, BTS) and Cu SAZ were combined with PV to create PSB. BTS were able to release SO2 before inducing SO3− that can cause cell apoptosis. In addition, it can also down-regulate glutathione (GSH) while up-regulating H2O2 to significantly improve the catalytic ability of Cu SAZ. This study proved that PSB could suppress over 90% of the tumor while displaying good tumor-targeting abilities alongside great biocompability. Thus, by innovatively combining gas therapy with NCT, the system developed in this study not only provide a new strategy for addressing peritoneal metastasis of gastric cancer, but also offers useful insights into designing a new generation of cancer therapy for potential clinical applications.

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives.

Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.

Accurate and Rapid Detection of Peritoneal Metastasis from Gastric Cancer by AI-Assisted Stimulated Raman Molecular Cytology.

Peritoneal metastasis (PM) is the mostcommon form of distant metastasis and one of the leading causes of death in gastriccancer (GC). For locally advanced GC, clinical guidelines recommend peritoneal lavage cytology for intraoperative PM detection. Unfortunately, current peritoneal lavage cytology is limited by low sensitivity (<60%). Here the authors established the stimulated Raman molecular cytology (SRMC), a chemical microscopy-based intelligent cytology. The authors firstly imaged 53 951 exfoliated cells in ascites obtained from 80 GC patients (27 PM positive, 53 PM negative). Then, the authors revealed 12 single cell features of morphology and composition that are significantly different between PM positive and negative specimens, including cellular area, lipid protein ratio, etc. Importantly, the authors developed a single cell phenotyping algorithm to further transform the above raw features to feature matrix. Such matrix is crucial to identify the significant marker cell cluster, the divergence of which is finally used to differentiate the PM positive and negative. Compared with histopathology, the gold standard of PM detection, their SRMC method could reach 81.5% sensitivity, 84.9% specificity, and the AUC of 0.85, within 20 minutes for each patient. Together, their SRMC method shows great potential for accurate and rapid detection of PM from GC.

Predicting postoperative gastric cancer prognosis based on inflammatory factors and machine learning technology

ObjectiveThere is a strong association between gastric cancer and inflammatory factors. Many studies have shown that machine learning can predict cancer patients’ prognosis. However, there has been no study on predicting gastric cancer death based on machine learning using related inflammatory factor variables.MethodsSix machine learning algorithms are applied to predict total gastric cancer death after surgery.ResultsThe Gradient Boosting Machine (GBM) algorithm factors accounting for the prognosis weight outcome show that the three most important factors are neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and age. The total postoperative death model showed that among patients with gastric cancer from the predictive test group: The highest accuracy was LR (0.759), followed by the GBM algorithm (0.733). For the six algorithms, the AUC values, from high to low, were LR, GBM, GBDT, forest, Tr and Xgbc. Among the six algorithms, Logistic had the highest precision (precision = 0.736), followed by the GBM algorithm (precision = 0.660). Among the six algorithms, GBM had the highest recall rate (recall = 0.667).ConclusionPostoperative mortality from gastric cancer can be predicted based on machine learning.

LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer

Metastasis constitutes one of the major causes of tumor-related death in gastric cancer (GC), and understanding key events in the initiation of this phenotypic switch may provide therapeutic opportunities. Long noncoding RNAs (lncRNAs) are emerging as molecules that play vital roles in tumorigenesis and metastasis. In this study, we aimed to identify metastasis-related lncRNAs in the context of GC. The lncRNAs overexpressed in tumor tissues and positively associated with overall survival were screened out using the TCGA database. qPCR assays in clinical samples showed that LINC00858 was significantly upregulated in GC tissues compared with normal counterparts. Functional analysis suggested that LINC00858 depletion attenuated the migration, and invasion of cancer cells in vitro and suppressed the metastasis of xenografted tumors in vivo. Mechanistically, LINC00858 could interact with the metastasis-associated RAN and stabilize its protein expression by decreasing posttranslational ubiquitination. The transcription factor YY1 could bind to the promoter of LINC00858 to upregulate its expression in GC cells. Moreover, overexpression of YY1 and RAN was positively associated with upregulation of LINC00858 in GC tissues. Our results suggest that LINC00858 might play a role in GC metastasis, and be a diagnostic biomarker and potential therapeutic target.

A novel 450-nm laser-mediated sinoporphyrin sodium-based photodynamic therapy induces autophagic cell death in gastric cancer through regulation of the ROS/PI3K/Akt/mTOR signaling pathway.

Photodynamic therapy (PDT) has become an ideal and promising therapeutic method for fighting cancer, but its common application in clinical practice is prevented by the limitations of expensive devices in light sources and phototoxicity in photosensitizers. The aim of this study was to explore the antitumor efficiency of the novel 450-nm blue laser (BL) combined with sinoporphyrin sodium (DVDMS)-mediated PDT against human gastric cancer (GC) in vitro and in vivo, focusing on autophagy pathway. Cell viability was detected by Cell Counting Kit-8 and colony formation assays in HGC27, MGC803, AGS, and GES-1 cells. Cell apoptosis was measured by flow cytometry and western blotting. The production of reactive oxygen species (ROS) was measured by fluorescence microscopy and flow cytometry. Autophagy was determined by transmission electron microscopy and western blotting. The antitumor effect of BL-PDT in vivo was detected by a subcutaneous tumor model in nude mice. The novel 450-nm laser-mediated DVDMS-based PDT caused remarkable growth inhibition and apoptosis induction in GC cells in vitro by the production of excessive ROS. Autophagy flux was induced by BL-PDT in GC cells, as determined by LC3 conversion assay, LC3 turnover assay, and mRFP-GFP-LC3 puncta assay. Furthermore, autophagy induction was demonstrated to positively contribute to BL-PDT-induced apoptotic effects on GC cells. Mechanically, ROS/PI3K/Akt/mTOR pathway was identified to involve in the regulation of BL-PDT-induced autophagy as determined by transcriptomic analysis and functional studies. Consistently, xenograft studies confirmed the significant antitumor effect of BL-PDT and its favorable safety in vivo. The novel 450-nm laser-mediated DVDMS-based PDT may be a safe and effective approach against GC. Our results thus provide compelling evidence for the therapeutic application of BL-PDT in human GC.

Isoquercitrin Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Gastric Cancer Cells.

Isoquercitrin is a natural flavonoid quercetin with anti-inflammatory, anti-anaphylactic, antiviral, and anticancer activities. Here, we investigated the effect of isoquercitrin on immunogenic cell death (ICD) of gastric cancer (GC). The effect of isoquercitrin on GC cell lines (AGS and HGC-27) was evaluated using cell counting kit-8 assays, colony formation assays, Annexin V/PI apoptosis detection kit, western blot analysis, JC-1 staining, immunofluorescence assays, and enzyme-linked immunosorbent assay. Isoquercitrin at doses greater than 20μM had significant inhibitory effects on the survival of GC cell lines, including HGC-27, AGS, MKN-45, and SNU-1. Isoquercitrin treatment decreased GC cell colony formation in a dose-dependent manner and induced apoptosis accompanied by downregulation of BCL-2 and upregulation of BAX, cleaved caspase-3, and caspase-12. In addition, isoquercitrin promoted the disruption of mitochondrial membrane potential in GC cells. The GC cell surface levels of calreticulin (CRT) and extracellular levels of CRT, ATP, and HMGB1 were enhanced by treatment with isoquercitrin. The protein levels of HMGB1, HSP70, and HSP90 were upregulated by isoquercitrin in a dose-dependent manner. Moreover, the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyrate reversed isoquercitrin-induced ICD in GC cells. Overall, our data suggested that isoquercitrin induces ER stress and ICD in GC cells. Isoquercitrin may be a candidate anticancer drug for the treatment of GC.

The management of Helicobacter pylori infection and prevention and control of gastric cancer in China.

Helicobacter pylori (H. pylori) infection, a type-1 carcinogen, was closely associated with gastric cancer (GC). Successfully eradicating H. pylori infection could reduce the incidence of GC. China was a country with high incidence of GC and high prevalence of H. pylori infection. Nearly half of worldwide GC new cases and deaths attributed to H. pylori infection occurred in China. H. pylori prevalence varied over time with the improvement of socioeconomic status and sanitary conditions. The knowledge of antibiotic resistance rate in time was important to guide the clinical choice of antibiotics use in the regimens. With the publication of five Chinese consensus reports on the management of H. pylori infection and the effort of public preach of H. pylori-related knowledge, the standardization of H. pylori diagnosis and treatment by clinicians was improved. Bismuth-containing quadruple therapy was widely applied in clinical practice of H. pylori eradication because of high efficacy and safety. High-dose Proton Pump Inhibitor-amoxicillin dual therapy or vonoprazan-amoxicillin dual therapy showed comparable efficacy and lower side effects than bismuth-containing quadruple therapy, which were the alternative choice. The diagnosis rate of early GC was low and distinguishing Chinese GC risk population for the further endoscopy screening was important. Efforts have been done to establish prediction models to stratify GC risk in the Chinese GC risk population. We reviewed the current situation of the management of H. pylori infection and prevention and control of GC in China here.

Trend of gastric cancer incidence and death rate in adolescents and young adults: A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database.

Less attentions are paid into the adolescents and young adults (AYAs) diagnosed with gastric cancer (GC). Our study aims to explore incidence rate trend, death rate trend, and prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in AYAs with GC. A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database was performed. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) with 95% confidence interval (CI) for incidence and death rate trends. Prognostic factors for OS and CSS were investigated using Cox proportional hazard model and gray test, respectively, with results shown as hazard ratio (HR) with 95% CI. Although no statistical significance, incidence rate trend showed a tendency to an increase in AYAs (AAPC=0.2, 95% CI: -0.2-0.6). All-cause death rate trends were declined both in AYAs and middle-aged and elderly people (MAEP), with AAPC value of -0.6 (95% CI: -0.8 to -0.5) and -0.5 (95% CI: -0.6 to -0.4), respectively. AYAs had a lower risk of all-cause death (HR: 0.87, 95% CI: 0.84-0.90) but a higher risk of GC-specific death (HR: 1.11, 95% CI: 1.07-1.15) than MAEP. Chemotherapy (HR: 1.27, 95% CI: 1.16-1.40) and intraoperative radiation (HR: 2.89, 95% CI: 1.13-7.37) were, respectively, identified as risk factors for worse OS and CSS in AYAs. AYAs had a higher risk of GC-specific death, indicating more attention should be paid into AYAs with GC.

Predicting Gastric Intestinal Metaplasia in a High-Risk Population.

Gastric intestinal metaplasia (GIM) is a precancerous lesion. It has a low prevalence rate in the United States. However, GIM is more common among non-White and immigrant populations. Harlem Hospital serves a community that includes predominantly African Americans,Hispanics, and immigrants from West Africa and Spanish-speaking Caribbean countries. This study aims to define the factors predicting GIM in this high-risk group as well ashelp define screening strategies for vulnerable populations. A total of 1351 patients who underwent endoscopic gastroduodenoscopy (EGD) and biopsy in 2018 and 2019 for any indication at Harlem Hospital were included in this study. Gastric biopsy specimens taken during the procedure were assessed for GIM by histopathology. Baseline demographics were collected, including age, sex, and ethnicity. Other information collected included risk factors for GIM such as Helicobacter pylori infection, smoking status, and the use of alcohol. Descriptive analysis was done and the Wilcoxon rank sum test and chi-squared test were used to test for associations. Multiple logistic regressions were used to assess the odds of independent factors associated with increased risk of GIM. Of the 1351 patients reviewed, 106 had GIM for a prevalence of 8.0% (CI: 6.7%-9.6%, p < 0.001). Univariate analysis revealed older patients, males, history of smoking, alcohol, and H. pylori infection were significantly associated with GIM. Using multiple logistic regressions and adjusting for underlying risk factors, smoking (OR: 1.61, 95% CI: 1.00-2.570) and H. pylori infection (OR: 3.35, 95% CI: 2.18-5.15)continued to be significantly associated with increased risk of GIM; however, alcohol use was not significant after adjusting for other risk factors (OR: 1.10, 95% CI: 0.68-1.78). Hispanic risk for GIM was slightly higher than African Americans (OR: 1.17, 95% CI: 0.74-1.83). The predicted marginal effect of age on the odds of GIM was significant from age 40 and increased exponentially at age 50. By age 70, the odds of GIM were as high as 11% (95% CI: 8.3-13.6). The prevalence of GIM in our population is significantly higher compared to reported cases in the United States. Age, male gender, H. pylori infection, and smoking significantly increasethe risk of GIM. Given the high prevalence of GIM in our population, early endoscopic screening would play an important role in evaluating dyspepsia to diagnose GIM with or without H. pylori infection. We propose screening all at-risk ethnicities from age 40 years with EGD according to the Sydney System biopsy protocol. We believe this will ultimately decrease the incidence of gastric cancer death in these vulnerable populations of color.

Dietary zinc intake and mortality in patients with intestinal-type gastric cancer: A prospective cohort study in Korea

Current evidence regarding the association between zinc intake and gastric cancer (GC)-specific survival in patients with intestinal-type GC is lacking. Therefore, this cohort study investigated the association between zinc intake and GC mortality through follow-up on GC death among patients with intestinal-type GC and whether these effects differ according to the source of zinc intake. A total of 185 patients with intestinal-type GC were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys. A total of 178 patients were included and analyzed. The median follow-up period was 7.3 years. In the fully adjusted models, the highest tertile of total zinc intake showed a significantly lower GC mortality than the lowest tertile (hazard ratio, 0.22; 95% confidence interval: 0.08-0.64). In addition, the tertile of total zinc intake showed a dose-response association with GC mortality (p=0.015). Analysis of the source of zinc intake revealed that when zinc intake from staples (rice and noodles), animal, and plant food sources were combined, the results were similar to those of total zinc intake and GC mortality. Zinc intake through various foods may be effective in reducing GC mortality by achieving balance with other nutrients. Our results suggest that zinc improves the survival of patients with intestinal-type GC in Korea.

Sex and age differences in mortality trends of gastric cancer among Hispanic/Latino populations in the United States, Latin America, and the Caribbean

An up-to-date analysis of gastric cancer mortality among Hispanic/Latino populations is required for estimating disease burden and assessing the effectiveness of clinical and preventive strategies. We retrieved gastric cancer deaths between 1997 and 2017 (as available) from the Surveillance, Epidemiology, and End Results Program (United States Hispanics) and the World Health Organization databases (Puerto Rico, 16 Latin American and Caribbean countries). Joinpoint regression analysis was used to examine trends in age-standardized mortality rates (ASMR; per 100 000 person-years) and calculate average annual percent changes (AAPCs) by country (or territory), age group (25-49 and ≥50 years), and sex. Trends were compared to assess slope parallelism. In 2017, Chile (31·8), Colombia (24·3) and Costa Rica (24·3) had the highest ASMR of gastric cancer for men, while Guatemala (17·2), Peru (13·5), and Costa Rica (13·3) had the highest ASMR for women. Small-to-moderate mortality declines (AAPCs ranged -4 to -0.5%) were observed between 1997 and 2017. In almost all countries, trends decreased among individuals aged ≥50 years. However, age-specific trends were not parallel (p-values <0.05) in Brazil, Colombia, Mexico, the United States, and Venezuela for both men and women, and in five additional countries for only women; with a few countries showing stable or slightly increasing trends for individuals aged 25-49 years. Overall gastric cancer mortality rates in Hispanics/Latinos declined in the last two decades. However, there was a notable variation in trends by country, sex, and age group. Continued and targeted prevention efforts are needed to reduce the disease burden in these vulnerable populations. Universidad Cientifica del Sur, Peru, and National Cancer Institute, United States.

COL1A1 and PTGS2 as potential core genes in gastric cancer

Background: Gastric Cancer (GC) is highly prevalent in China, where its mortality rate accounts for 50% of global GC deaths. Currently, GC pathogenesis is not fully understood

Regional disparities in trends of global gastric cancer incidence and mortality from 1990 to 2019

Objective: To depict gastric cancer burden trends globally and analyze geographical and socioeconomic disparities among different countries and territories. Methods: We extracted the data from Global Burden of Disease 2019 Database. We conducted the Joinpoint regression and calculated the average annual percent change (AAPC) and corresponding 95% confidence interval (CI) for age-standardized gastric cancer incidence and mortality from 1990 to 2019. Linear regression was performed to measure the association of sociodemographic index (SDI) with each country's gastric cancer incidence and mortality AAPC. We applied the age-period-cohort analysis to assess the cohort effect on gastric cancer incidence and mortality. Results: The AAPCs for gastric cancer age-standardized incidence and mortality rates from 1990 to 2019 were -1.27% (95% CI: -1.43%, -1.11%) and -1.87% (95% CI: -2.01%, -1.72%), respectively. SDI levels were negatively associated with AAPCs, which means that countries with higher SDI had higher AAPC (P<0.001). The decrease of gastric cancer burden in countries with low or medium SDI levels was slower than that globally. The age-period-cohort analysis indicated that countries with higher SDI levels had more apparent decline in birth cohort effects from 1900 to 1999. Conclusions: Countries with different socioeconomic levels have various decreasing rates for gastric cancer incidence and deaths. Countries with higher SDI levels have higher declining rates for gastric cancer burden.

Recommendations for Gastric Cancer Screening in Korean Americans

In the United States, Korean Americans have the highest incidence rate of gastric cancer and have a five times higher risk than non-Hispanic Whites. Early detection is important for cancer treatment and survival. In countries where there is a high prevalence of gastric cancer, such as Korea and Japan, national screening programs have been implemented. In the United States, immigrants of countries like Korea and Japan continue to have many of the same risk factors as in their home country. However, recommendations for gastric cancer screening in the United States are lacking, even for these high-risk populations. We conducted a literature search of relevant information to identify appropriate screening measures and criteria for gastric cancer screening for Korean Americans. Based on the data from the Korean national screening program, the proportion of gastric cancers diagnosed at an earlier stage increased significantly. Furthermore, endoscopic screening was associated with a decrease of about 50% in gastric cancer death risk for those between 40 and 74 years old. Therefore, there is a similar need for screening for Korean Americans who have a similar diet and lifestyle as native Koreans. By increasing early detection, routine screening via endoscopy in high-risk Korean Americans may have a significant impact on decreasing the morbidity and mortality associated with gastric cancer, as seen in the Korean studies.

HMMR promotes peritoneal implantation of gastric cancer by increasing cell–cell interactions

BackgroundDistant metastasis is the prominent factor for cancer-induced death of gastric cancer in which peritoneum is one of the dominating targets of gastric cancer metastasis. However, there is still a lack of effective predictive indicators and treatment methods for gastric cancer patients with peritoneal metastasis.MethodsA clustering assay was used to investigate the cell aggregates formation ability. While the soft agar assay and anoikis assay were performed to detect the anchorage-independent growth and anoikis-resistant ability respectively. Luciferase activity assay, western blotting and immunofluorescence were used to explore the effect of HMMR on AKT signaling activity. The peritoneal implantation model was examined to explore the role of HMMR in vivo.ResultsSilencing of HMMR expression markedly reduced the peritoneal metastasis of gastric cancer cells through reducing cell–cell interactions. Mechanistically, HA-HMMR could activate Akt signaling, thus succeeding in distant colonization and metastatic outgrowth. Importantly, inducible depletion of HMMR significantly abrogates peritoneal implantation of gastric cancer in vitro and in vivo.ConclusionOur study highlights that HMMR promotes peritoneal implantation of gastric cancer. A better understanding of HMMR’s functions and mechanism might provide a novel therapeutic target and prognostic marker for metastatic gastric cancer.

A predictive model for early death in elderly patients with gastric cancer: A population-based study

BackgroundThe mean age of gastric cancer (GC) patients has increased due to the aging society. Elderly GC patients with poor physical status tend to develop complications during the treatment courses, which cause early death. This study aimed to identify risk factors and establish nomograms for predicting total early death and cancer-specific early death in elderly GC patients.MethodsData for elderly GC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly assigned to a training cohort and a validation cohort. The univariate logistic regression model and backward stepwise logistic regression model were used to identify independent risk factors for early death. Nomograms were constructed to predict the overall risk of early death and their performance was validated by receiver operating characteristic (ROC) curve, calibration curve, decision curve analyses (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) in both training and validation cohorts.ResultsAmong the 3102 enrolled patients, 1114 patients died within three months from the first diagnosis and 956 of them died due to cancer-specific causes. Non-Asian or Pacific Islander (API) race, non-cardia/fundus or lesser/greater curvature, higher AJCC stage, no surgery and no chemotherapy were all related to a high risk of both all-cause early death and cancer-specific early death. Higher T stage and N0 stage were only positively related to total early mortality, while liver metastasis was only positively related to cancer-specific early mortality. Based on these identified factors, two nomograms were developed for predicting the risk of all-cause and cancer-specific early death, which showed good performance with the AUC of the nomograms were 0.775 and 0.766, respectively. The calibration curves, DCAs, NRI, and IDI also confirmed the value of these nomograms.ConclusionsThese nomogram models were considered a practical tool to identify the early death of elderly GC patients and help provide a more individualized treatment strategy.

Profiling of gene fusion involving targetable genes in Chinese gastric cancer.

BACKGROUNDApproximately half of all new cases of gastric cancer (GC) and related deaths occur in China. More than 80% of patients with GC are diagnosed at an advanced stage, which results in poor prognosis. Although HER2-directed therapy and immune checkpoint inhibitors have been somewhat successful, new drugs are still needed for the treatment of GC. Notably, several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors, including GC, such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers. However, gene fusions involving targetable genes have not been well characterized in Chinese patients with GC.AIMTo identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC.METHODSWe retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC. Clinicopathological characteristics were obtained from their medical records. Genetic alterations, such as single nucleotide variants, indels, amplifications, and gene fusions, were identified using a targeted sequencing panel containing 825 genes. Fusions were validated by fluorescence in situ hybridization (FISH) using break-apart probes. The microsatellite instability (MSI) status was evaluated using MSIsensor from the targeted sequencing panel data. Tumor mutational burden (TMB) was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region. Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC.RESULTSWe found that 1.68% (16/954) of patients harbored 20 fusion events involving targetable genes. RARA fusions (n = 5) were the most common, followed by FGFR2, BRAF, MET, FGFR3, RET, ALK, EGFR, NTRK2, and NRG1 fusions. Two of the RARA fusions, EML4-ALK (E6:E20) and EGFR-SEPTIN14 (E7:E10), have been identified in other tumors but not in GC. Surprisingly, 18 gene fusion events were previously not reported in any cancer types. Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes, such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA- and ligand-binding domains of RARA. Consistent with the results of detection using the targeted sequencing fusion panel, the results of FISH (fluorescence in situ hybridization) confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09, respectively. Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification (P = 0.02); however, there were no significant differences between fusion-positive and fusion-negative patients in age, sex, MSI status, and TMB.CONCLUSIONWe characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.

Benefit-to-harm ratio and cost-effectiveness of government-recommended gastric cancer screening in China: A modeling study.

ObjectiveCurrent guidelines recommend the gastric cancer risk score scale (GCRSS) for screening in gastric cancer (GC) high-risk populations in China. This study aimed to estimate the clinical benefits, harms, cost, and cost-effectiveness of the GCRSS screening strategy from a Chinese healthcare system perspective.Materials and methodsUsing a microsimulation model, we evaluated 7 screening scenarios of the GCRSS with varying starting ages. We simulated 100,000 individuals from the age of 20 for each screening scenario. The main outcomes included GC incidence reduction, number of cause-specific deaths, costs, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER), and benefit-to-harm ratio. Deterministic and probabilistic sensitivity analyses were done to explore the robustness of model findings.ResultsScreening with the GCRSS strategy at the age of 40 years (40-GCRSS) provided the greatest reduction of GC incidence by 70.6%, with 7,374 GC deaths averted per 100,000 individuals and the lowest benefit-to-harm ratio of 0.392. Compared with no screening or previous less costly strategy, at a willingness-to-pay (WTP) threshold of $37,655 per QALY, the 40-GCRSS strategy was cost-effective, with ICERs of $12,586 and $29,115 per QALY, respectively. Results were robust across univariate and probabilistic sensitivity analyses. The 40-GCRSS strategy showed a 0.856 probability of being cost-effective at a $37,655 per QALY WTP threshold.ConclusionsThe findings suggest that the GCRSS strategy is effective and cost-effective in reducing the GC disease burden in China from a Chinese healthcare system perspective. Screening from the age of 40 would be the optimal strategy.