Gastric Cancer Research Articles

Downregulation of short-stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β-catenin signaling.

Gastric cancer (GC) a prevalent form of cancer globally. Previous research suggests that SHOX2 may have a role in promoting cancer progression. However, the role of SHOX2 in GC is not well understood. Based on data from TCGA_GC data set, SHXO2 levels were examined in normal and GC tissues. Patients in the TCGA_GC cohort were divided into high- and low-SHOX2 level groups for analysis of overall survival (OS), functional enrichment, and immune infiltration. Furthermore, experiments were conducted to investigate the impact of SHOX2 on GC cell function through gain- and loss-of-function experiments. Utilizing data from public databases, SHOX2 mRNA levels were found to be elevated in GC tissues compared to normal control, this finding was confirmed by RT-qPCR, western blot analysis, and immune-histochemical analyses. Elevated SHOX2 levels could serve as an independent indicator of poor prognosis in GC patients. Furthermore, SHOX2 levels had a negative correlation with CD8 T cells and CD4 memory activated T cells, and a positive correlation with of M0 macrophages in GC patients. Functional analyses revealed that SHOX2 deficiency notably suppressed GC cell proliferation, migration, and invasion. Additionally, SHOX2 deficiency was shown to suppress stemness in GC cells in vitro and in vivo via inactivating wnt/β-catenin signaling. Collectively, SHOX2 may serve as a prognostic marker for GC patients, and downregulation of SHOX2 could effectively impede GC cell growth and stemness by inactivating the wnt/β-catenin signaling pathway. These findings underscore the potential of SHOX2 as a promising therapeutic target for GC.

Circ_0006089 facilitates gastric cancer progression and oxaliplatin resistance via miR-217/NRP1

BackgroundOxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown. MethodsCirc_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells. ResultsThe findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217. ConclusionCirc_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.

Prohibitin 2 confers NADPH oxidase 1 -mediated cytosolic oxidative signaling to promote gastric cancer progression by ERK activation

Oxidative signaling plays a dual role in tumor initiation and progression to malignancy; however, the regulatory mechanisms of Oxidative stress in gastric cancer remain to be explored. In this study, we discovered that Prohibitin 2 (PHB2) specifically regulates cytosolic reactive oxygen species production in gastric cancer and facilitates its malignant progression. Previously, we found that PHB2 is upregulated in gastric cancer, correlating with increased tumorigenicity of gastric cancer cells and poor patient prognosis. Here, we discovered that PHB2 expression correlates with the activation of the ERK/MAPK cascade, positively regulating the top gene NADPH oxidase 1 (NOX1) within this pathway. Further mechanistic investigation reveals that PHB2 enhances NOX1 transcription by interacting with the transcription factor C/EBP-beta and promoting its translocation into the nucleus, resulting in elevated intracellular oxidative signaling driven by NOX1, which subsequently activates ERK. Therefore, we propose that targeting PHB2-C/EBP-beta-NOX1-mediated cytosolic oxidative stress could offer a promising therapeutic avenue for combating gastric cancer malignant progression.

MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway

Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren’s intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer.

The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can engage in the malignant biological behaviors of tumors through various mechanisms. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelial- mesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.

Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy.

A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes. Epirubicin delivery to gastric cancer cells using mesenchymal stem cells. In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS. Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05). We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM via miR-29 in GC.

Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism. An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA. Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed. In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial.

This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.

Comparison Between Billroth II and Billroth II + Braun Anastomosis in Gastrectomy for Gastric Cancer

IntroductionDistal gastrectomy remains the predominant therapeutic approach for gastric cancer, with digestive tract reconstruction as an integral procedure. The implementation of Braun anastomosis following Billroth II anastomosis is common in distal gastrectomy. This retrospective cohort study evaluated the clinical utility of Braun anastomosis by comparing the outcomes and quality of life between Billroth II (B-II) and Billroth II with Braun (B-IIB) anastomosis in the treatment of gastric cancer. MethodsA retrospective cohort study examined clinical and pathological data from 377 patients who underwent distal gastrectomy for gastric cancer treatment at The Affiliated Lihuili Hospital, Ningbo University, from October 2016 to October 2021.185 patients received B-II anastomosis, while the other 192 received B-IIB anastomosis, forming the B-II and B-IIB groups, respectively. Baseline characteristics, perioperative variables, short-term and long-term complications, and nutritional indicators at 1 mo and 1 y postsurgery were compared across both groups. Additionally, gastric endoscopy results at 6 mo and 1 y postsurgery were evaluated. Quality of life at 1 y postsurgery was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. ResultsBaseline characteristics between the two groups revealed no statistically significant differences (all P > 0.05), confirming their equivalence. All 377 patients successfully underwent curative distal gastrectomy for gastric cancer without intraoperative procedural modifications. No intraoperative complications or perioperative mortality occurred. Notable differences included extended operative time (222.1 ± 41.0 vs. 199.4 ± 24.9 min, P < 0.001), reduced postoperative nasogastric tube removal time (1.8 ± 0.9 vs. 2.2 ± 1.1 d, P < 0.001), decreased average gastric drainage volume (100.7 ± 35.2 vs. 112.2 ± 32.0 mL, P = 0.001), and increased incidence of internal hernia and ileus (4.7% vs. 1.1% and 8.3% vs. 3.2%, P = 0.038 and P = 0.035) in the B-IIB group compared to the B-II group. No significant differences were observed in estimated blood loss, lymph node dissection, postoperative flatus time, transition to a semiliquid diet, length of hospital stay, or short-term and long-term complications (all P > 0.05). Nutritional assessments conducted 1 mo and 1 y postsurgery indicated no statistically significant differences in body mass index, total protein, and serum albumin levels between the two groups (all P > 0.05). Gastric endoscopy evaluations at 6 mo and 1 y postsurgery, including food residue grade, gastritis severity, extent of gastritis, and bile reflux, demonstrated no significant discrepancies between the groups (all P > 0.05). At the 1-y follow-up, neither group exhibited tumor recurrences, deaths from tumor-related diseases, postoperative complications, or other diseases. Additionally, quality of life assessments using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core revealed no significant differences across various domains or items between the groups (all P > 0.05). ConclusionsA comparative analysis between B-II and B-IIB anastomosis demonstrated no notable variations in intraoperative parameters, postoperative nutritional outcomes, gastric endoscopic results, or postoperative quality of life. Nevertheless, incorporating Braun anastomosis can extend the duration of surgery and may elevate the likelihood of postoperative internal hernia.

Assessing the Value of 68Ga-FAPI PET/CT in Gastric Mucinous Adenocarcinoma or Signet Ring Cell Carcinoma.

Purpose To investigate the clinical impact and prognostic value of gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in gastric mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRCC). Materials and Methods Eighty-six participants with newly diagnosed or recurrent gastric MAC or SRCC were prospectively enrolled from April 2021 to October 2021 and underwent both fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT and 68Ga-FAPI PET/CT. The sensitivity, specificity, and accuracy of the two scans in primary and metastatic tumors were evaluated using the McNemar test. Changes of treatment strategies were recorded to compare the treatment management value of the two PET/CT scans. The maximum standardized uptake value (SUVmax) and peritoneal cancer index (PCI) were recorded for survival analysis. Progression-free survival (PFS) was defined as the time interval from the date of PET/CT scans to the date of disease progression. Results Eighty-six participants (median age, 62 years [IQR, 45-78 years]; 49 female) were evaluated. 68Ga-FAPI PET/CT showed higher diagnostic accuracy in detecting involved lymph nodes (87% [212 of 244] vs 71% [173 of 244], P < .001) and peritoneal metastases (96% [70 of 73] vs 55% [40 of 73], P < .001) than 18F-FDG PET/CT. Twenty-six participants (30% [26 of 86]) had treatment changes due to more accurate diagnosis with 68Ga-FAPI PET/CT. Additionally, the 68Ga-FAPI PCI was an independent predictor for PFS (hazard ratio, 6.9; 95% CI: 2.1, 23.1; P = .002). Conclusion 68Ga-FAPI PET/CT had higher accuracy in diagnosis of gastric MAC/SRCC compared with 18F-FDG PET/CT and demonstrated the potential to improve treatment strategies and predict prognosis. Keywords: PET/CT, Mucinous Adenocarcinoma, Signet Ring Cell Carcinoma, Oncology, Abdomen/GI, Molecular Imaging Supplemental material is available for this article. © RSNA, 2024.

ASO Author Reflections: Neoadjuvant Chemotherapy Combined with Immunotherapy is a Promising Strategy for Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma.

ASO Author Reflections: Neoadjuvant Chemotherapy Combined with Immunotherapy is a Promising Strategy for Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma.

Comprehensive Clinicopathologic Features in Autoimmune Atrophic Gastritis: Insights from a European Cohort of 57 Patients

ContextAutoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis. ObjectiveTo thoroughly describe the histological features of a European cohort of AAG patients. DesignClinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed. ResultsThirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76%). Vitamin B12 levels were low (< 200pg/ml) in 37/54 patients (69%). Serum gastrin levels was elevated (> 115pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35%). Histologically, deep chronic inflammation was present in 46/57 (81%) patients. Complete destruction of oxyntic glands was observed in 45/57 (79%) patients. Pyloric metaplasia was present in 54/57 (95%) patients, intestinal metaplasia in 51/57 (89%) patients, and pancreatic metaplasia in 20/57 (35%) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients. ConclusionsThe diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

Ras-related Protein in Brain 4A (Rab4A) is Downregulated by miR-496 to inhibit the Progression of Gastric Cancer.

Ras-related protein in brain 4A (Rab4A), as a member of the Rab family, is involved in the intracellular circulation of membrane receptors or endocytic substances and regulates the progression of multiple tumors. From our results, the knockdown of Rab4A inhibited the proliferation, migration and invasion in AGS cells. Importantly, the surface expression of epidermal growth factor receptor (EGFR) declined significantly in Rab4A knockdown cells. The downstream pathway of EGFR was also inhibited after the transfection of Rab4A-specific siRNA, including AKT and β-catenin pathways. In addition, miR-496 down-regulated the expression of Rab4A in AGS cells. The result of the luciferase reporter assay showed that miR-496 could bind to the 3'UTR of Rab4A. In conclusion, the expression of Rab4A is inhibited by miR-496, and the knockdown of Rab4A inhibits the proliferation, migration and invasion through down-regulating the surface expression of EGFR. Rab4A is a potential target in the treatment of gastric cancer.

Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

The Long-Term Results of Proximal Gastrectomy for Proximal Gastric Cancer: A Propensity Score Matching Analysis Based on SEER Database.

Proximal gastrectomy (PG) is one of function-preserving gastrectomy (FPG). In this study, we compared the long-term results of proximal gastric cancer (PGC) patients undergoing proximal gastrectomy and total gastrectomy (TG). Patients diagnosed with PGC and receiving PG or TG between 2004 and 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was applied to minimize confounding factors. Kaplan-Meier analysis and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between the PG and TG groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS. A total of 3916 patients were recruited according to the inclusion and exclusion criteria, with 2614 undergoing PG and 1302 undergoing TG. After 1:1 PSM matching, 912 pairs of data were included for analysis. Before PSM matching, PG group tended to have better OS and CSS outcomes. However, after PSM matching, both surgical approaches showed similar long-term results. PG for PGC yields comparable long-term outcomes to TG and demonstrates safety in terms of oncologic outcomes.

Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.

Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer

Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%). H. pylori infection causes GC in &gt;98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.

RE: A real-world survey on expensive drugs used as first-line chemotherapy in patients with HER2-negative unresectable advanced/recurrent gastric cancer in the stomach cancer study group of the Japan clinical oncology group.

RE: A real-world survey on expensive drugs used as first-line chemotherapy in patients with HER2-negative unresectable advanced/recurrent gastric cancer in the stomach cancer study group of the Japan clinical oncology group.

Gastric neoplasm detection of computer-aided detection-assisted esophagogastroduodenoscopy changes with implement scenarios: a real-world study.

The implementation of computer-aided detection (CAD) devices in esophagogastroduodenoscopy (EGD) could autonomously identify gastric precancerous lesions and neoplasms and reduce the miss rate of gastric neoplasms in prospective trials. However, there is still insufficient evidence of their use in real-life clinical practice. A real-world, two-center study was conducted at Wenzhou Central Hospital (WCH) and Renmin Hospital of Wuhan University (RHWU). High biopsy rate and low biopsy rate strategies were adopted, and CAD devices were applied in 2019 and 2021 at WCH and RHWU, respectively. We compared differences in gastric precancerous and neoplasm detection of EGD before and after the use of CAD devices in the first half of the year. A total of 33 885 patients were included and 32 886 patients were ultimately analyzed. In WCH of which biopsy rate >95%, with the implementation of CAD, more the number of early gastric cancer divided by all gastric neoplasm (EGC/GN) (0.35% vs 0.59%, P=0.028, OR [95% CI]=1.65 [1.0-2.60]) was found, while gastric neoplasm detection rate (1.39% vs 1.36%, P=0.897, OR [95% CI]=0.98 [0.76-1.26]) remained stable. In RHWU of which biopsy rate <20%, the gastric neoplasm detection rate (1.78% vs 3.23%, P<0.001, OR [95% CI]=1.84 [1.33-2.54]) nearly doubled after the implementation of CAD, while there was no significant change in the EGC/GN. The application of CAD devices devoted to distinct increases in gastric neoplasm detection according to different biopsy strategies, which implied that CAD devices demonstrated assistance on gastric neoplasm detection while varied effectiveness according to different implementation scenarios.

Machine learning algorithms able to predict the prognosis of gastric cancer patients treated with immune checkpoint inhibitors

BACKGROUND Although immune checkpoint inhibitors (ICIs) have demonstrated significant survival benefits in some patients diagnosed with gastric cancer (GC), existing prognostic markers are not universally applicable to all patients with advanced GC. AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models. METHODS Data from 273 patients diagnosed with GC and distant metastasis, who un-derwent ≥ 1 cycle(s) of ICIs therapy were included in this study. Patients were randomly divided into training and test sets at a ratio of 7:3. Training set data were used to develop the machine learning models, and the test set was used to validate their predictive ability. Shapley additive explanations were used to provide insights into the best model. RESULTS Among the 273 patients with GC treated with ICIs in this study, 112 died within 1 year, and 129 progressed within the same timeframe. Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting (XGBoost), logistic regression, and decision tree. After comprehensive evaluation, XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival. CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy. Patient nutritional status may, to some extent, reflect prognosis.