• Helicobacter pylori
• Jinghua Weikang capsule
• bismuth-containing quadruple therapy
• multi-center randomized controlled study
• rescue treatment

• Clinical value
• Gastric cancer
• Noninvasive diagnosis and screening
• Oral contrast-enhanced ultrasound
• Tumor-node-metastasis staging

• Humans
• Stomach Neoplasms/diagnostic imaging
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Neoplasm Staging/methods
• Contrast Media/administration & dosage
• Middle Aged
• Male
• Ultrasonography/methods
• Female
• Predictive Value of Tests
• Aged
• Adult
• Lymphatic Metastasis/diagnostic imaging
• Sensitivity and Specificity
• China/epidemiology
• Gastrectomy/methods
• Preoperative Care/methods
• Neoplasm Invasiveness

• Apoptosis
• Cell cycle
• Schiff bases
• Temperature
• Viability
• Western blot

• Humans
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemical synthesis
• Antineoplastic Agents/chemistry
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Chitosan/chemistry
• Chitosan/pharmacology
• ErbB Receptors/antagonists & inhibitors
• ErbB Receptors/metabolism
• Green Chemistry Technology
• Polyethylene Glycols/chemistry
• Polyethylene Glycols/pharmacology
• Protein Kinase Inhibitors/pharmacology
• Protein Kinase Inhibitors/chemical synthesis
• Protein Kinase Inhibitors/chemistry
• Pyrazoles/pharmacology
• Pyrazoles/chemical synthesis
• Pyrazoles/chemistry
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/pathology

• LH2022H063 Heilongjiang Provincial Natural Science Foundation of China

• HER2
• IHC
• MS-SRM
• gastric cancer
• mixed classification
• types identification

• computational biology and bioinformatics
• biomarkers

Gastric Carcinoma is the fourth leading cause of cancer deaths worldwide, in which stomach adenocarcinoma (STAD) is the most common histological type. A growing amount of evidence has suggested the importance of enhancer RNAs (eRNAs) in the cancer. However, the potential mechanism of eRNAs in STAD remains unclear. The eRNAs-regulated genes (eRRGs) were identified through four different enhancer resources. The differentially expressed eRRGs were obtained by ‘DESeq2’ R package. The prognosis prediction model was constructed by Cox and Lasso regression analysis. The ‘ChAMP’ R package and ‘maftools’ R package were used to investigate the multi-omics characters. In this study, combining the concept of contact domain, a total of 9014 eRRGs including 4926 PCGs and 4088 lncRNAs were identified and these eRRGs showed higher and more stable expression. Besides, the functions of these genes were mainly associated with tumor-related biological processes. Then, a prognostic prediction model was constructed and the AUC values of the 1-, 3- and 5-year survival prediction reached 0.76, 0.84 and 0.84, respectively, indicating that this model has a high accuracy. Finally, the difference between high-risk group and low-risk group were investigated using multi-omics data including gene expression, DNA methylation and somatic mutations. Our study provides significant clues for the elucidation of eRNAs in STAD and may help improve the overall survival for STAD patients.

Studies have confirmed the prognostic value of the expression status of human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer. However, its role in early gastric cancer (EGC) remains largely unknown. This study explored the association between HER2 overexpression and clinical outcomes of patients with EGC.

A total of 211 patients who had undergone endoscopic treatment for pN0 EGC were enrolled. The HER2 expression status was assessed using immunohistochemistry (IHC).

The prevalence of HER2 overexpression was 14.2%. HER2 overexpression showed a significant correlation with tumor location (P = 0.033). Multivariate analysis showed that HER2 overexpression was significantly associated with an increased risk of tumor recurrence in pN0 EGC (hazard ratio [HR] = 3.97; 95% confidence interval [CI] 1.30–12.14; P = 0.016) but not overall survival (OS) or disease-specific survival (DSS). Of the included patients, age was associated with OS (HR = 1.11; 95% CI 1.04–1.18; P = 0.002], whereas lymphovascular invasion was significantly associated with poor DSS (HR = 33.66; 95% CI 3.05–371.25; P = 0.004).

This study shows that HER2 overexpression is significantly associated with tumor recurrence in pN0 EGC. Hence, Her2 testing at diagnosis is important and differential treatment and/or follow up strategies for patients with Her2 overexpression may merit future study.

The online version contains supplementary material available at 10.1186/s12876-022-02309-7.

• Early gastric cancer
• Human epidermal growth factor receptor 2
• Mortality
• Overexpression
• Tumor recurrence

Gastric cancer (GC) shows high metastasis and low survival. RNA modification writers play critical roles in tumor development. This study examined the clinical significance of RNA modification writers in GC prognosis based on four types of adenosine modifications (m¹A, m⁶A, APA and A-to-I).

Writers demonstrated high mutation and expression in GC patients. Different expressions of 26 RNA modification writers were differentially associated with GC prognosis. High-WM score group appeared worse overall survival, higher immune infiltration and activation of EMT pathways than low-WM score group. WM score was correlated with both miRNAs-targeted signaling pathways and patients’ sensitivity to chemotherapeutic drugs and efficacy of immunotherapy.

This study further revealed the close association between adenosine-related RNA modifications and progression of GC. A cross talk between EMT and RNA modification was identified to be one of the mechanisms underlying GC development. Our WM scoring system could serve as a clinical indicator for predicting GC prognosis. Importantly, the WM score could guide personalized treatments such as chemotherapy and immunotherapy for GC patients.

The online version contains supplementary material available at 10.1186/s40246-022-00386-z.

• Bioinformatics analysis
• Epithelial–mesenchymal transition (EMT)
• Gastric cancer
• Prognosis
• RNA modifications
• Tumor microenvironment (TME)
• Writers

Gastric cancer (GC) is a malignancy with a high incidence and mortality. The tumor immune microenvironment plays an important role in promoting cancer development and supports GC progression. Accumulating evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune evasion. In this review, we systematically summarize the intricate crosstalk between GC cells and immune cells, including tumor-associated macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, effector T cells, regulatory T cells, and B cells. We focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune attack. We conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies, both alone and in combination with conventional therapies. Anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC treatment. However, the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC patients. This review provides a comprehensive understanding of the immune evasion mechanisms of GC, and highlights promising immunotherapeutic strategies.

• Gastric cancer
• Immune evasion
• Immune checkpoint
• Immunotherapy
• Microenvironment

Mucinous gastric carcinoma (MGC) is a rare histological type of gastric carcinoma. Calcifications, seen on imaging and histopathological preparations, and which are infrequent in other types of gastric carcinoma, are characteristic of MGC. We present a patient with MGC with calcifications of the gastric wall and describe the computerized tomography (CT) features of the lesion and changes in the calcifications before and after chemotherapy.

A 61-year-old man was admitted to our hospital in May 2020 because of a large, tender abdominal mass. Abdominal CT showed diffuse, irregular thickening of the gastric walls, with miliary and punctate calcifications. There were metastases to the perigastric and retroperitoneal lymph nodes and also peritoneal seeding. Histological examination of a specimen obtained by endoscopic biopsy showed poorly differentiated calcified signet-ring cell gastric cancer. The patient was clinically staged with T4N+M1 disease. He was treated with docetaxel, cisplatin, and fluorouracil as first-line therapy, irinotecan combined with S-1 as second-line chemotherapy, and programmed cell death protein 1 as third-line therapy. The patient underwent a total of nine cycles of chemotherapy. Follow-up CT scans every 3 mo showed continually increasing calcifications. As of this writing, the patient has survived almost 1 year.

In this case report, we describe the histopathological and imaging characteristics of a patient with gastric cancer receiving chemotherapy. Multiple punctate calcifications were seen, which gradually increased during chemotherapy. Several possible mechanisms for the calcifications are described, but further research is needed. Future findings may lead to new approaches for the evaluation and treatment of such tumors.

• Gastric cancer
• Calcification
• Computerized tomography
• Chemotherapy
• Prognosis
• Case report

Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients.

We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model.

Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV⁺ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV⁺ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV (MSI or EBV⁺ cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], P = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], P<0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], P <0.001) but not PD-L1-positive MSS/EBV GCs.

Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.

• Epstein-Barr virus
• Gastric cancer
• Overall survival
• PD-L1
• Postoperative chemotherapy
• Microsatellite instability

Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo.

A subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of β-catenin, GSK-3β, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3β, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining.

PBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3β, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of β-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3β and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues.

The PBMF concocted herein exerts anti-gastric cancer activities via epithelial–mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/β-catenin signaling pathway.

The online version contains supplementary material available at 10.1186/s12906-021-03301-6.

• Epithelial–mesenchymal transition
• Gastric cancer
• Medicinal food
• Wnt/β–catenin signaling pathway

It has been reported that the expression of Krüppel-like factor 17 (KLF17) was associated with the occurrence, development, invasion, metastasis and chemotherapy resistance of various tumors. However, the detailed mechanisms by which KLF17 promotes chemotherapy resistance in gastric cancer (GC) have not been fully investigated. In the present study, we collected the GC tissues and non-tumor tissues (matched adjacent normal tissues with corresponding GC tissues) of 60 GC patients, used qRT-PCR, Western blot and immunohistochemistry assay to analyze the relationship between the expression of KLF17 and the clinical pathological data of the patients. The effect of KLF17 on the sensitivity of GC cell lines to 5-fluorouracil (5-FU), and the potential mechanism were detected by MTS assay, Flow cytometry assay, and Western blot. Compared with non-tumor tissues, the expression level of KLF17 in GC tissue was significantly down-regulated, and the expression level of KLF17 in GES-1 cell line and GC cell lines also had a similar trend. Down-regulated expression of KLF17 is related to tumor size, invasion, regional lymph node metastasis, and TNM staging. Furthermore, through upregulating the expression of KLF17, the sensitivity of BGC-823 and SGC-7901 cell lines to 5-FU was obviously increased. Mechanistically, upregulation the expression of KLF17 can inhibit the expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and B-Cell lymphoma-2 (BCL-2), which have been reported to be associated with drug resistance and cell proliferation. Collectively, these data implied that KLF17 has the biological effect of inhibiting chemotherapy resistance of GC, and it could be a potential strategy for the GC chemotherapy resistance.

• 5-fluorouracil
• KLF17
• chemotherapy resistance
• gastric cancer

• Gastric cancer
• disease burden
• prediction
• risk factor
• temporal trend

To study the effects of z-guggulsterone on gastric cancer cell apoptosis and the mechanism related.

Human gastric tumor SGC-7901 cells and GES-1 normal epithelial cells were treated with z-guggulsterone (0–75 μM) for 24 h. MTT assay was applied to evaluate cell proliferation. Flow cytometry and Hoechst staining were used to assess cell apoptosis. Western blotting was applied to evaluate FXR, small heterodimer partner (SHP), Bcl-2, and Bax protein expression. ELISA was applied to gain the levels of active caspase-3 and the contents of TNF-α, TGF-β1, and VEGF.

The expression levels of FXR and SHP were higher in tumor cells than in normal epithelial cells. Inhibition of FXR signaling with z-guggulsterone dose-dependently inhibited SGC-7901 cell proliferation and promoted SGC-7901 cell apoptosis. Bcl-2 protein expression was significantly decreased, and active caspase-3 and Bax protein expression was increased in SGC-7901 cells incubated with z-guggulsterone. The content of TNF-α was significantly increased, and the contents of VEGF and TGF-β1 were decreased in SGC-7901 cells incubated with z-guggulsterone.

Inhibition of FXR signaling with z-guggulsterone induced anticancer effects in SGC-7901 cells by decreasing cell proliferation and promoting apoptosis. Z-guggulsterone induced cell apoptosis through the mitochondria-dependent pathway.

• LncRNA
• apoptosis
• cell proliferation
• gastric cancer
• invasion
• metastasis

• Animals
• Apoptosis/genetics
• Biomedical Research
• Cell Proliferation/genetics
• Humans
• Protein Biosynthesis/genetics
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Signal Transduction
• Stomach Neoplasms/genetics

The pursuit of health has always been the driving force for the advancement of human society, and social development will be profoundly affected by every breakthrough in the medical industry. With the arrival of the information technology revolution era, artificial intelligence (AI) technology has been rapidly developed. AI has been combined with medicine but it has been less studied with gastric cancer (GC). AI is a new budding star in GC, and its contribution to GC is mainly focused on diagnosis and treatment. For early GC, AI’s impact is not only reflected in its high accuracy but also its ability to quickly train primary doctors, improve the diagnosis rate of early GC, and reduce missed cases. At the same time, it will also reduce the possibility of missed diagnosis of advanced GC in cardia. Furthermore, it is used to assist imaging doctors to determine the location of lymph nodes and, more importantly, it can more effectively judge the lymph node metastasis of GC, which is conducive to the prognosis of patients. In surgical treatment of GC, it also has great potential. Robotic surgery is the latest technology in GC surgery. It is a bright star for minimally invasive treatment of GC, and together with laparoscopic surgery, it has become a common treatment for GC. Through machine learning, robotic systems can reduce operator errors and trauma of patients, and can predict the prognosis of GC patients. Throughout the centuries of development of surgery, the history gradually changes from traumatic to minimally invasive. In the future, AI will help GC patients reduce surgical trauma and further improve the efficiency of minimally invasive treatment of GC.

• Gastric cancer
• Artificial intelligence
• Gastroscopy
• Lymph node
• Robotic surgery
• Minimally invasive

Hyperin is an effective monomer extracted from Malvaceae plant Abelmoschus, which is a flavonol glycoside compound. Hyperin performs a variety of pharmacological activities, such as analgesia, antioxidation, anti-inflammation, avoiding microthrombosis, regulating immune function, inhibiting tumor cell growth. But the role of Hyperin on gastric cancer is unrevealed. Considering the essential role of Hyperin, Hyperin function in gastric cancer is necessary to explore.

To identify the function of Hyperin in gastric cancer.

The role of Hyperin on gastric cell progression was detected in our research. Proliferation, migration, and invasion ability were assessed by the CCK-8, colony formation, cell-cycle assay, wound healing, Transwell migration and invasion assays. TUNEL assay and flow cytometry showed the results of the apoptosis level. Further, caspase-3, -9 activity and apoptosis-associated protein were assessed by the Caspase activity kit and Western blot. Wnt/β-catenin signal pathway activity was appraised by TOP/FOP luciferase activity. Immunohistochemical staining was performed to detect the role of Hyperin on tumor growth in vivo.

Functional experiments showed that Hyperin inhibited proliferation, migration, and invasion and induced apoptosis in gastric cancer cells. Meanwhile, Hyperin prevented tumor growth by suppressing Wnt/β-catenin signal pathway.

The present study revealed that Hyperin suppressed gastric cancer progression by controlling Wnt/β-catenin signal pathway, which provided a novel therapy in gastric cancer.

• Hyperin
• Wnt
• gastric cancer
• β-catenin