Gastric Cancer Patients Research Articles

Preoperative malnutrition in elderly gastric cancer patients and adverse postoperative outcomes of radical gastrectomy

Malnutrition is not only a prevalent condition among the elderly but also a common comorbidity in elderly people with gastric cancer (GC). Malnutrition is closely linked to high rates of postoperative complications and poor wound healing in elderly GC patients, which may lead to a higher incidence and mortality rate of GC. Malnutrition decreases the physical function of elderly GC patients after surgery, severely affecting their postoperative life quality and hindering subsequent treatments. This retrospective study was conducted by Zhao et al , focusing on the clinical baseline data, postoperative complications, and hospitalization times of elderly GC patients who underwent curative gastrectomy. Additionally, the underlying causes of poor outcomes for patients were discussed. This study may provide a solid basis for the clinical treatment of elderly GC patients in the future. Therefore, malnutrition can serve as a negative prognostic factor for curative surgery in GC patients. Addressing malnutrition and its adverse effects can benefit elderly GC patients from surgical treatment.

Immunotherapy for metastatic gastric cancer

This editorial discusses the article written by Chen et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery . The current study found that programmed cell death 1 ligand 1 (PD-L1) expression is considered as one of the pan-cancer biomarkers of immune checkpoint inhibitors (ICIs) treatment response. Four molecular subtypes are widely used to guide and evaluate the prognosis and diagnosis and treatment of gastric cancer (GC) patients. Clinical trials of ICI treatment including Nivolumab, Pembrolizumab, Avelumab have been conducted for metastatic GC (mGC). The effects of various single agent ICIs on mGC therapy varied. ICIs combined with chemotherapy can indeed bring survival benefits to patients with mGC. Combining ICIs with chemotherapy can give more patients the chance of surgery in the treatment of GC transformation. However, not all PD-L1 positive patients can benefit from it. It is urgent to find better biomarkers to predict the response of ICIs for more precise clinical treatment.

Predicting prolonged postoperative ileus in gastric cancer patients based on bowel sounds using intelligent auscultation and machine learning

BACKGROUND Prolonged postoperative ileus (PPOI) delays the postoperative recovery of gastrointestinal function in patients with gastric cancer (GC), leading to longer hospitalization and higher healthcare expenditure. However, effective monitoring of gastrointestinal recovery in patients with GC remains challenging because of the lack of noninvasive methods. AIM To explore the risk factors for delayed postoperative bowel function recovery and evaluate bowel sound indicators collected via an intelligent auscultation system to guide clinical practice. METHODS This study included data from 120 patients diagnosed with GC who had undergone surgical treatment and postoperative bowel sound monitoring in the Department of General Surgery II at Shaanxi Provincial People's Hospital between January 2019 and January 2021. Among them, PPOI was reported in 33 cases. The patients were randomly divided into the training and validation cohorts. Significant variables from the training cohort were identified using univariate and multivariable analyses and were included in the model. RESULTS The analysis identified six potential variables associated with PPOI among the included participants. The incidence rate of PPOI was 27.5%. Age ≥ 70 years, cTNM stage (I and IV), preoperative hypoproteinemia, recovery time of bowel sounds (RTBS), number of bowel sounds (NBS), and frequency of bowel sounds (FBS) were independent risk factors for PPOI. The Bayesian model demonstrated good performance with internal validation: Training cohort [area under the curve (AUC) = 0.880, accuracy = 0.823, Brier score = 0.139] and validation cohort (AUC = 0.747, accuracy = 0.690, Brier score = 0.215). The model showed a good fit and calibration in the decision curve analysis, indicating a significant net benefit. CONCLUSION PPOI is a common complication following gastrectomy in patients with GC and is associated with age, cTNM stage, preoperative hypoproteinemia, and specific bowel sound-related indices (RTBS, NBS, and FBS). To facilitate early intervention and improve patient outcomes, clinicians should consider these factors, optimize preoperative nutritional status, and implement routine postoperative bowel sound monitoring. This study introduces an accessible machine learning model for predicting PPOI in patients with GC.

Advances in artificial intelligence for predicting complication risks post-laparoscopic radical gastrectomy for gastric cancer: A significant leap forward

In a recent paper, Hong et al developed an artificial intelligence (AI)-driven predictive scoring system for potential complications following laparoscopic radical gastrectomy for gastric cancer patients. They demonstrated that integrating AI with random forest models significantly improved the preoperative prediction and patient outcome management accuracy. By incorporating data from multiple centers, their model ensures standardization, reliability, and broad applicability, distinguishing it from the prior models. The present study highlights AI's potential in clinical decision support, aiding in the preoperative and postoperative management of gastric cancer patients. Our findings may pave the way for future prospective studies to further enhance AI-supported diagnoses in clinical practice.

A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery

Background: Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery. Methods: In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared. Results: Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p<0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K/Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival. Conclusion: Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.

Effect of Intensive Nursing Management on Quality of Life and Mental Health in Elderly Gastric Cancer Patients Undergoing Chemotherapy: A Retrospective Study

Aims/Background Implementing effective nursing management is particularly critical in the case of elderly gastric cancer (GC) patients receiving chemotherapy, who are more vulnerable to risk events. Therefore, this study explored the effect of intensive nursing management on quality of life (QoL) and mental health in elderly GC patients receiving chemotherapy. Methods A total of 155 elderly patients with GC undergoing chemotherapy in Central Hospital Affiliated to Shandong First Medical University from July 2021 to July 2023 were selected as the study subjects. The sample was divided into two groups according to different nursing methods: 74 patients who received intensive nursing management were classified in the observation group, while 81 patients treated with routine nursing management were classified under the reference group. The QoL, mental health and adverse reactions to chemotherapy were compared between the two groups. Results Before nursing management was implemented, there was no significant difference in the scores of the quality of life questionnaire-core 30 (QLQ-C30), patient health questionnaire-9 items (PHQ-9), and the Chinese version of the M.D. Anderson Symptom Inventory (MDASI-C) (p > 0.05). After management, in comparison with the reference group, the observation group showed significantly higher scores in each dimension of QLQ-C30, as well as significantly lower scores in PHQ-9 and MDASI-C (p < 0.001). The incidences of gastrointestinal reaction, myelosuppression, neurotoxicity, and hepatorenal damage were lower in the observation group than in the reference group (45.95% vs 70.37%, 40.54% vs 65.43%, 35.14% vs 53.09%, and 33.78% vs 51.25%, respectively; p < 0.05). Conclusion The application of intensive nursing management in treating elderly GC patients during chemotherapy effectively improves their physical and mental states, ameliorates clinical symptoms and enhances the QoL, showing certain clinical application value.

Application of Intelligent Management Model Based on Electronic Patient-Reported Outcome During Immunotherapy in Patients with Gastric Cancer: A Single-Center Retrospective Study

Aims/Background Gastric cancer is the third leading cause of cancer-related death worldwide, which seriously affects the health of patients. Immunotherapy is a commonly used clinical treatment for gastric cancer, but the adverse events caused by it seriously affect the prognosis of patients. Therefore, it is necessary to control and manage the disease risk of patients during immunotherapy. To explore the effect of applying an intelligent management model based on electronic patient-reported outcome (ePRO) in patients with gastric cancer during immunotherapy. Methods The clinical data of 184 gastric cancer patients receiving immunotherapy in The Fourth Hospital of Hebei Medical University from September 2021 to September 2023 were retrospectively analyzed. Ninety patients receiving ePRO-based intelligent management were selected, and 85 patients were included in the observation group after excluding 5 patients. For the reference group, 94 patients receiving common case management were selected, with 90 patients being included after excluding 4 patients. After 6 months of follow-up, the nutritional status score, quality of life, treatment compliance and adverse events were compared between the two groups. Results No significant difference was detected in nutritional status and World Health Organization Quality of Life-BREF (WHOQOL-BREF) scores of the patients before discharge (p > 0.05). After 2 months of follow-up, compared with the reference group, the observation group had a higher proportion of patients in grade A and grade B, which was not statistically significant (p > 0.05), and significantly higher physiological and psychological scores (p < 0.001), but showed no meaningful differences in other fields (p > 0.05). After 4 months of follow-up, the nutritional status in the observation group was significantly improved (p < 0.05), and the subjects displayed higher WHOQOL-BREF scores (p < 0.05) than those in the reference group. No significant difference in the incidence of adverse events was detected (p > 0.05). After 6 months of follow-up, the treatment compliance of the observation group was 83.53%, which was significantly higher than that of the reference group (70.00%; p < 0.05). Conclusion The intelligent management model based on ePRO is conducive to improving the nutritional status of patients with gastric cancer during immunotherapy, as well as enhancing their quality of life and treatment compliance, making it worthy of clinical application.

Overestimation of clinical N-staging in microsatellite instable gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics

Abstract Background Microsatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation. Materials and methods We conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors. Results Multivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts. Conclusion Frequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options.

Linking CDH1 SNPs to gastric cancer risk: a comprehensive analysis of rs16260, rs13689, and rs9929218.

Single nucleotide polymorphisms (SNPs) are linked to carcinogenesis. Pathogenic variants in the CDH1 gene are associated with gastric cancer. This study examines the genotype and allele frequencies of three SNPs (rs16260, rs13689, and rs9929218) in the CDH1 gene and their relationship with gastric cancer risk. The study involved 105 gastric cancer patients with pathology results and 105 healthy controls. Clinical, histopathological, and demographic data were collected and compared between the two groups. No significant differences were found for rs16260 (-160 C > A) and rs9929218 (G > A) between patients and controls (p > 0.05). For rs13689 (T > C), the T allele frequency was 90% in patients versus 69% in controls, while the C allele frequency was 10% in patients versus 31% in controls. A significant difference was observed for this SNP, with a higher T allele frequency in patients (OR = 4.03 CI95% 2.4-6.7, p < 0.0001) compared with controls, suggesting a fourfold increased risk of gastric cancer. Genotype frequencies were 80% wild-type (TT) and 20% heterozygous-type (TC) in patients, and 58% TT, 22% TC, and 20% mutant-type (CC) in controls (p < 0.0001). The frequencies of non-C allele carriers (TT) were present in 80% of patients versus 58.1% of controls (OR = 2.88 CI95% 1.56-5.34, p = 0.0006). This study is the first to link the rs13689 SNP's T allele and TT genotype with increased gastric cancer risk. Our results suggest that thers13689 T allele may contribute significantly to disease susceptibility, while thers16260 CC genotype and rs9929218 GG genotype may influence risk in smokers.

SLITRK2 as a prognostic and immunological biomarker in gastric cancer.

SLIT and NTRK-like protein 2 (SLITRK2) encodes a transmembrane protein that regulates neurite outgrowth. Some studies have demonstrated that SLITRK2 overexpressed in glioma. But the expression pattern, prognostic value and immunologic function of SLITRK2 in tumors remains unknown. The expression pattern of SLITRK2 among pan-cancers was examined through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). We analyzed the association between SLITRK2 expression level and tumor stage among pan-cancers. Kaplan-Meier survival analysis was utilized to investigate the prognostic relevance of SLITRK2 across 33 different types of cancers. Moreover, the correlations among SLITRK2 expression, immune cell infiltration, immunomodulatory related genes, tumor mutation burden (TMB), microsatellite instability (MSI) were evaluated. The relationship between SLITRK2 expression and crucial genes mutations was also illustrated. By using tissue microarray (TMA), the expression of SLITRK2 in 89 paired gastric cancer (GC) tissues was investigated. Our study indicated that SLITRK2 expression varied across cancers. Elevated SLITRK2 expression was positively related to advanced tumor stage, poor overall survival (OS) and reduced disease-free survival (DFS). Bioinformatic analyses underscore SLITRK2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Based on TMA data, SLITRK2 expression level was positively associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients. Our findings provided that SLITRK2 may function as a biomarker by regulating immune cell infiltration. In addition, we verified that high SLITRK2 expression was correlated with poor prognosis in GC.

Fra-1 affects chemotherapy sensitivity by inhibiting ferroptosis in gastric cancer cells

Aim: Gastric cancer (GC) is one of the common malignant tumors, and most patients with advanced GC often develop chemotherapy resistance, resulting in poor chemotherapy efficacy. Therefore, it is crucial to clarify the specific mechanisms of their chemotherapy resistance. Methods: In this study, we analyzed the correlation between fos-related antigen-1 (Fra-1) and chemotherapy resistance in GC using bioinformatics, cell counting kit-8 (CCK8), and 5-ethynyl-2’-deoxyuridine (EDU) combined with flow cytometry; furthermore, we used energy metabolomics sequencing, combined with ChIP-qPCR technology, to elucidate the specific role of Fra-1 in chemotherapy resistance of GC cells and its related mechanisms. Results: We found that high Fra-1 expression was closely related to chemotherapeutic drugs in GC cells, as demonstrated by bioinformatics analysis combined with EDU and CCK8 experiments. Energy metabolomics combined with in vitro cellular experimental analysis revealed that the pentose phosphate pathway (PPP) was activated in GC cells with high Fra-1 expression, along with an increase in the synthesis of metabolites such as nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), a decrease in the level of reactive oxygen species (ROS), and the inhibition of their ferroptosis. In addition, ChIP-qPCR experiments confirmed that Fra-1 binds to the promoter of glucose-6-phosphate dehydrogenase (G6PD), a key rate-limiting enzyme of the PPP, and transcriptionally regulates its expression, which in turn activates the PPP and promotes chemotherapy resistance in GC cells. Conclusion: Our research findings suggest that Fra-1 activates the PPP by upregulating G6PD transcriptional activity and inhibiting its ubiquitination level, inhibiting ferroptosis in GC cells and inducing chemoresistance. This provides an experimental basis for screening potential molecular targets for chemotherapy resistance in GC patients.

Single-cell data revealed the regulatory mechanism of TNK cell heterogeneity in liver metastasis from gastric cancer.

The present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations. GC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment. Based on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand-receptor pairs. The GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat. Single-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k-Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand-receptor pairs existed between the GC and GC liver metastasis groups. This study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy: A systematic review and meta-analysis

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy: A systematic review and meta-analysis

Expression of HECTD2 predicts peritoneal metastasis of gastric cancer and reconstructs immune microenvironment.

Peritoneal metastasis (PM) is a common metastasis site and death cause of gastric cancer, which is a complex biological process, but there is currently a lack of effective prediction and treatment targets. In this study, we first analyzed the differential gene expression of gastric cancer patients with or without peritoneal metastasis, and identified the HECT domain E3 ubiquitin protein ligase 2 (HECTD2) as the core gene of PM in gastric cancer. The current study shows that the role of HECTD2 in tumor is contradictory. In this study, our results show that the low expression of HECTD2 indicates that the survival rate of overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), and disease-free survival (DFS) are better, and can be used as an important component of prognostic indicators. In addition, through pathway enrichment analysis, we found that HECTD2 was mainly involved in metastasis related pathways such as extracellular matrix remodeling and cell adhesion in gastric cancer, and high expression of HECTD2 could activate epithelial-mesenchymal transition (EMT) metastasis related pathways in gastric cancer. In regulating the metastasis of gastric cancer cells, HECTD2 can also change the surrounding microenvironment, induce the enrichment of interstitial components and build an immune microenvironment conducive to tumor progression, while patients with low expression of HECTD2 may be more likely to benefit from immunotherapy. In conclusion, HECTD2 may be a novel biomarker for the diagnosis and prognosis of peritoneal metastasis of gastric cancer, providing basis for the mechanism of peritoneal metastasis of cancer and clinical medication.

Textbook oncological outcome of locally advanced gastric cancer patients with preoperative sarcopenia: a multicenter clinical study.

The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI < 36.4 cm2/m2 in males and < 28.4 cm2/m2 in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P = 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

ARID1A is a Coactivator of STAT5 that Contributes to CD8+ T Cell Dysfunction and Anti-PD-1 Resistance in Gastric Cancer.

ARID1A deletion mutation contributes to improved treatment of several malignancies with immune checkpoint inhibitors (ICIs). However, its role in modulating of tumor immune microenvironment (TIME) of gastric cancer (GC) remains unclear. Here, we report an increase of CD8+ T cells infiltration in GC patients with ARID1A-mutation (MUT), which enhances sensitivity to ICIs. Kaplan-Meier survival analysis showed that ARID1A-mutation patients with gastrointestinal malignancies benefit from immunotherapy. Transcriptome analysis implicated that ARID1A regulates STAT5 downstream targets to inhibit T-cell mediated toxicity. Integrated dual luciferase assay and ChIP-qPCR analyses indicated that ARID1A coordinated with STAT5 to facilitate the transcription of the immunosuppressive factors TGF-β1 and NOX4. ARID1A recruited canonical BAF complex (cBAF) subunits, including SMARCB1 and SMARCD1, to sustain DNA accessibility. Downregulation of ARID1A reduced chromatin remodeling into configurations which make GC more sensitive to ICIs. In addition, targeting STAT5 effectively improved anti-PD-1 efficiency in ARID1A-wild type (WT) GC patients. Taken together, ARID1A is a coactivator of STAT5, function as a chromatin organizer in GC ICIs resistance, and targeting STAT5 is an effective strategy to improve the efficiency of ICIs in GC.

DNA hypomethylation of INHBA promotes tumor progression and predicts prognosis and immune status of gastric cancer.

Gastric cancer (GC) is characterized by its high malignancy and poor prognosis. However, the role of Inhibin subunit beta A (INHBA) in GC remains insufficiently understood. This study aims to comprehensively evaluate the clinical significance, biological roles, and possible mechanisms of INHBA in GC. Expression levels and survival analyses of the Inhibin beta family were assessed using online databases. A prediction model based on INHBA was developed. In addition, the associations between INHBA expression and immune status, and chemotherapy sensitivity were explored. In vitro experiments were conducted to investigate the biological impact of INHBA on GC cells. Pyrosequencing and the DNA methylation inhibitor, 5-AZA-2'-deoxycytidine (5-AZA-dC) were employed to elucidate the mechanisms underlying INHBA function. Our findings revealed that INHBA exhibited high expression in GC patients, and elevated INHBA expression correlated with worse outcomes. We developed a novel nomogram incorporating INHBA, age, and tumor node metastasis (TNM) stage to predict the prognosis of GC patients. Additionally, INHBA was found to be associated with suppressed infiltration of immune cells and chemosensitivity. Functionally, INHBA promoted the proliferation and invasiveness of GC cells. Mechanistically, pyrosequencing revealed DNA Hypomethylation of INHBA in the first exon region, and the effects of INHBA silencing were rescued by 5-AZA-dC treatment. Our study suggests that DNA hypomethylation of INHBA contributes to the progression of GC. Furthermore, INHBA holds promise as a valuable biomarker for prognostic evaluation and immune status prediction in GC patients.

A screen-and-treat strategy for eradication of Helicobacter pylori among patients with family history of gastric cancer in a diverse U.S. population.

Screening and eradication of Helicobacter pylori (H. pylori) reduce the risk of gastric cancer in patients with family history. We assessed patient perspectives on H. pylori screening and treatment within a diverse regional U.S. Between July and August 2022, we conducted a cross-sectional study among patients with ≥1 first-degree relative with gastric cancer. Eligible patients were between 18-75 years of age without history of H. pylori infection or gastric cancer. A survey assessed interest in testing and willingness to complete treatment for H. pylori. Interested patients were offered H. pylori testing and treatment. We examined interest and effectiveness of treatment by race and ethnicity. We identified 15,255 eligible patients and 1,500 patients were randomly selected for the survey; 280 (19%) patients, including 2 relatives not initially invited but asked to participate, responded following outreach. Respondents were 65% male and averaged 57 years (SD=13) with 36% Hispanic, 36% non-Hispanic White, 15% Asian/Pacific Islander, 9% non-Hispanic Black. Overall, 223 (80%) were interested in H. pylori screening; of these, 89% would take antibiotics as prescribed. Willingness to screen was consistent across racial and ethnic groups. Among 223 respondents interested in screening, 128 (57%) completed testing with 15 screen-detected cases; all 15 completed treatment and 11 had confirmed eradication. Patients with family history of gastric cancer had a high level of interest in H. pylori screening and successful eradication when detected. A screen-and-treat strategy for H. pylori may be considered for patients with family history of gastric cancer.

The LINC01094/miR-545-3p/SLC7A11 Signaling Axis Promotes the Development of Gastric Cancer by Regulating Cell Growth and Ferroptosis.

This study aimed to investigate the role and mechanism of action of LINC01094 in the development of gastric cancer (GC). The expression levels of LINC01094 in GC patients and healthy individuals were analyzed online using the Cancer Genome Atlas database. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to determine the expression of LINC01094/miR-545-3p/SLC7A11 in GC tissues and cells. Functional experiments (MTT assay, colony formation assay, and flow cytometry) were conducted to assess the effect of LINC01094 and miR-545-3p on cell proliferation, viability, apoptosis, cell cycle, and reactive oxygen species. Correlations between LINC01094 and miR-545-3p, as well as SLC7A11, were analyzed and validated using the dual-luciferase reporter assay and RNA immunoprecipitation. The levels of Fe2+, malondialdehyde, and glutathione in the cells were measured biochemically, and the protein expression levels of Bcl-2, cleaved caspase3, Cyclin D1, and p21 were detected by Western blotting. LINC01094 was significantly upregulated in the GC tissues and cells with a targeting relationship with miR-545-3p; the expression levels of LINC01094 and miR-545-3p were negatively correlated. Knockdown of LINC01094 notably inhibited the proliferation and viability of GC cells and promoted cell ferroptosis, which, however, was abrogated by the silencing of miR-545-3p. These findings indicate that miR-545-3p could target and positively correlate with SLC7A11 expression. Additionally, LINC01094 could promote GC cell progression and affect cellular ferroptosis by regulating the miR-545-3p/SLC7A11 signaling axis.

Diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints.

Early detection is warranted to improve prognosis of gastric cancer (GC) but remains challenging. Liquid biopsy combined with machine learning will provide new insights into diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Here, we integrated the lipidomics data of three cohorts (n = 944) to develop the lipid metabolic landscape of GC. We further constructed the serum lipid metabolic signature (SLMS) by machine learning, which showed great performance in distinguishing GC patients from healthy donors. Notably, the SLMS also held high efficacy in the diagnosis of early-stage GC. Besides, by performing unsupervised consensus clustering analysis on the lipid metabolic matrix of patients with GC, we generated the gastric cancer prognostic subtypes (GCPSs) with significantly different overall survival. Furthermore, the lipid metabolic disturbance in GC tissues was demonstrated by multi-omics analysis, which showed partially consistent with that in GC serums. Collectively, this study revealed an innovative strategy of liquid biopsy for the diagnosis of GC on the basis of the serum lipid metabolic fingerprints.