Stomach adenocarcinoma (STAD) with microsatellite instability (MSI) is associated with a better prognosis compared to Non-MSI. This study aims to elucidate the differences in the tumor microenvironment (TME) of MSI and explore its underlying mechanisms in STAD.

TME differences between MSI and Non-MSI were analyzed using single-cell RNA sequencing (MSI = 7, Non-MSI = 19) and bulk RNA sequencing (MSI = 39, Non-MSI = 198). Differentially expressed genes (DEGs) were used to identify enriched pathways and hub genes. TNFSF9 expression was validated by immunohistochemistry (IHC) on 23 STAD sections (MSI = 13, Non-MSI = 10) and confirmed in tumor epithelial cells using SNU-1 (MSI) and AGS (Non-MSI) cell lines through quantitative polymerase chain reaction (qPCR) and Western blot (WB).

The results showed MSI was significantly associated with a better prognosis (P < 0.05). Within the TME, MSI was associated with a higher abundance of antigen-presenting cells, including M1 macrophages (40.1% vs. 27.9%) and activated dendritic cells (22.1% vs. 10.5%), as well as pro-inflammatory Th1-like CD4⁺ T cells (15% vs. 11%). However, MSI also showed an increase in exhausted T cells, indicating a complex immune landscape. Signaling pathway and cell communication analyses revealed an enrichment of cytokine-related pathways in MSI. Hub gene analysis revealed that TNFSF9 was predominantly expressed in stromal cells and partially in tumor epithelial cells in MSI, with its upregulation further confirmed through IHC, qPCR, and WB. Correlation analysis demonstrated a positive relationship between TNFSF9 expression and the abundance of M1 macrophages.

These findings provide new insights into the TME of MSI in STAD, emphasizing the significant role of TNFSF9 in shaping MSI-specific TME, enhancing immunotherapy efficacy, and improving patient survival.

Neoadjuvant chemotherapy (NAC) has been confirmed to improve the prognosis of patients with advanced gastric cancer (AGC). However, no study has investigated whether Helicobacter pylori (HP) infection affects the postoperative survival of patients who receive NAC.

This retrospective cohort study included 307 patients with AGC who underwent laparoscopic radical gastrectomy after NAC at three hospitals in China between January 1, 2016, and April 31, 2020. Cox regression was used to assess prognostic factors for survival. Kaplan-Meier was used for survival analysis.

The HP + and the HP- group included 141 and 166 cases. The 3-year overall survival (OS) and disease-free survival (DFS) of the HP + group were significantly better than the HP- group (3-year OS: 75.9% vs. 60.2%, 3-year DFS: 70.2% vs. 52.3%; All P < 0.001). For the HP + group, ypTNM Stage III (HR, 4.00; 95% CI, 1.11-14.39; P = 0.034), NAC ≥ 4 cycles (HR, 0.43; 95% CI, 0.20-0.90; P = 0.026), and adjuvant chemotherapy (AC) ≥ 4 cycles (HR, 0.20; 95% CI, 0.09-0.48; P < 0.001) are independent prognostic factors for OS. In the cohort of HP + patients who received ≥ 4 cycles of NAC, the prognosis of patients who received ≥ 4 cycles of AC after surgery was better than that of patients who received < 4 cycles of AC (3-year OS: 92.5% vs 71.4%; P = 0.042).

Following NAC, HP + patients with AGC exhibit better prognosis than that of HP- counterparts. For potentially resectable HP + AGC patients, radical surgery following ≥ 4 cycles of NAC with ≥ 4 cycles of sequential AC might be recommended to improve survival.

Microsatellite instability (MSI) is a phenotype characterized by changes in the sequence length of microsatellites in tumor cells and is closely linked to tumorigenesis and prognosis. Immune checkpoint inhibitors have shown good therapeutic effects in gastric cancer (GC) with MSI-high (MSI-H). However, the role of the novel immune checkpoint fibrinogen-like protein 1 (FGL1) in GC treatment has not been fully investigated. FGL1 expression in GC tissues and the difference in FGL1 immune infiltration between MSI/ microsatellite stability (MSS) patients were analyzed by bioinformatics and were verified in clinical samples. Xenograft models of MSS and MSI GC were constructed in human immune reconstitution mice, and FGL1 expression in tumors was detected. Immunofluorescence and immunohistochemistry were used to assay the infiltration of immune cells in the two types of mice. Cytotoxicity and chemotaxis tests were used to detect the toxicity and chemotaxis of CD8+T cells to GC cells, respectively. The cytokine content was detected by enzyme-linked immunosorbent assay. The therapeutic effects of FGL1 antibody on different types of GC were analyzed by xenograft mouse models. FGL1 exhibited significantly higher expression in GC, and its expression and immune cell infiltration levels were significantly higher in MSI GC than in MSS GC. CD8+T cells were significantly more effective in killing and chemotaxis of MSI GC cells than MSS GC cells. The FGL1 antibody was more effective in treating MSI GC.The novel immunosuppressor FGL1 antibody exerts a good therapeutic influence on MSI GC. These findings provide a basis for the development of drugs targeting FGL1 for MSI GC treatment.

This review addresses the current treatment paradigm and new advancements in the management of microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) esophagogastric cancer (EGC).

While chemotherapy and surgery remain the cornerstone of EGC treatment, MSI-H/dMMR tumors harbor high tumor mutational burden and represent a subset of patients who benefit from immune checkpoint inhibitors (ICI). ICI has been incorporated in the front line setting with and without chemotherapy for advanced disease. Recently, ICI has been studied in the perioperative setting for resectable disease. Though perioperative ICI results in improved response rates, it is not yet clear whether this translates to a survival benefit. Despite high response rates with ICI in this patient population, many do not respond to therapy, representing a major challenge in treatment. Preclinical studies have highlighted potential mechanisms of resistance which will guide drug development and clinical trials.

Accurate determination of microsatellite instability (MSI) status is critical for tailoring treatment approaches for gastric cancer patients. Existing clinical techniques for MSI diagnosis are plagued by problems of suboptimal time efficiency, high cost, and burdensome experimental requirements. Here, we for the first time establish the classification model of gastric cancer MSI status based on Raman spectroscopy. To begin with, we reveal that tumor heterogeneity-induced signal variations pose a prominent impact on MSI classification. To eliminate this issue, we develop Euclidean distance-based Raman Spectroscopy (EDRS) algorithm, which establishes a standard spectrum to represent the "most microsatellite stable" status. The similarity between each spectrum of tissues with the standard spectrum is calculated to provide a direct assessment on the MSI status. Compared to machine learning-algorithms including k-Nearest Neighbors, Random Forest, and Extreme Learning Machine, the EDRS method shows the highest accuracy of 94.6 %. Finally, we integrate the EDRS method with the clinical diagnostic modality, computed tomography, to construct an innovative joint classification model with good classification performance (AUC = 0.914, Accuracy = 94.6 %). Our work demonstrates a robust, rapid, non-invasive, and convenient tool in identifying the MSI status, and opens new avenues for Raman techniques to fit into existing clinical workflow.

This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy.

A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation.

Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR.

DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy.

This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area. Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version. Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Due to the large size and lack of fine-grained annotation, Whole Slide Images (WSIs) analysis is commonly approached as a Multiple Instance Learning (MIL) problem. However, previous studies only learn from training data, posing a stark contrast to how human clinicians teach each other and reason about histopathologic entities and factors. Here, we present a novel knowledge concept-based MIL framework, named ConcepPath, to fill this gap. Specifically, ConcepPath utilizes GPT-4 to induce reliable disease-specific human expert concepts from medical literature and incorporate them with a group of purely learnable concepts to extract complementary knowledge from training data. In ConcepPath, WSIs are aligned to these linguistic knowledge concepts by utilizing the pathology vision-language model as the basic building component. In the application of lung cancer subtyping, breast cancer HER2 scoring, and gastric cancer immunotherapy-sensitive subtyping tasks, ConcepPath significantly outperformed previous SOTA methods, which lacked the guidance of human expert knowledge.

Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications.

We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH.

In the univariate survival analysis for disease-specific survival, the Epstein-Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19-5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA's classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15-2.60], p = 0.009 and HR 1.74 [95% CI 1.06-2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial-mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30-2.77], p < 0.001) when compared with aberrant p53.

Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.

Quality health services could improve patient outcomes and prognosis. Gastric cancer care was of great disparity across genders. Disparities within radiotherapy units could impact gastric cancer care, potentially exacerbating gender-based inequalities.

We retrieved the disease burden data from Global Burden of Disease 2019. A quality of care index was constructed by applying principal component analysis techniques. The disparity of gastric cancer care across genders was described, and the association of access to radiotherapy with gastric cancer care as well as gender disparity was explored.

Males receive better quality of gastric cancer care than females, and this gender disparity is widening in middle-low socio-development regions. A positive correlation emerges between the density of radiotherapy facilities and an elevated quality of care, and reduced gender-based disparities.

The association between robust radiotherapy access, improved gastric cancer QCI, and reduced gender-based disparities spotlights the imperative of fortifying radiotherapy infrastructure within areas and populations in greatest need.

Pancreaticobiliary carcinomas rarely harbor targetable genetic alterations, including microsatellite instability (MSI) or neurotrophic tyrosine receptor kinase (NTRK) gene fusions. As these malignancies are typically present at an advanced stage and have suboptimal response to chemotherapy, the discovery of an actionable genomic alteration provides an additional avenue of treatment for chemotherapy-refractory cases.

In this study, we evaluate 319 cases of pancreaticobiliary carcinoma diagnosed on fine-needle aspiration biopsy or biliary brushing for DNA mismatch repair (MMR) protein deficiency and pan-TRK overexpression by immunohistochemistry (IHC) and compare these results to MSI and NTRK gene fusion molecular testing.

Although we find a high concordance between MMR protein IHC and MSI molecular testing in the evaluation of MMR deficiency and between pan-TRK IHC and NTRK fusion testing by next-generation sequencing, the low prevalence of either of these genetic alterations in our cohort casts doubt on the value of screening cases of pancreaticobiliary carcinoma for MMR protein deficiency and NTRK fusions.

As a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer.

The expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above.

Compared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years.

This study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.

Microsatellite instability (MSI) gastric cancer (GC) generally has a better prognosis than microsatellite-stable (MSS) GC and has been associated with nonsurvival benefit with the addition of chemotherapy (CMT) compared with surgery alone. However, patients with MSI have distinct clinicopathological characteristics. This study aimed to compare the survival outcomes between patients with MSI GC and those with MSS GC. In addition, this study analyzed the survival outcomes of patients with MSI GC who received CMT.

This study reviewed all patients with GC who underwent curative gastrectomy. Patients were divided into MSI group and the MSS group. Propensity score matching (PSM) was used to match clinicopathological factors.

Among the 378 patients enrolled, 78 (20.6%) had MSI. Older age (P < .001), subtotal gastrectomy (P = .008), pN0 (P = .020), and earlier pTNM stage (P = .012) were associated with MSI GC. Survival analysis showed better disease-free survival (DFS) and overall survival (OS) of patients in the MSI group (P = .012 and P = .019, respectively). After PSM, 78 patients were matched to each group. All variables assigned to the scores were well matched, and both groups became equivalent. After the matching, the differences in DFS and OS according to MSI/MSS status were estimated to be larger than before (DFS: 63.3% vs 41.4%; P = .002; OS: 65.8% vs 42.5%; P = .002). Regarding patients referred for CMT, there was no difference in DFS and OS between patients with MSI GC who underwent CMT and those who underwent surgery alone (P = .255 and P = .178, respectively).

Even after controlling for clinicopathological characteristics, MSI was identified as a prognostic factor for patient survival. MSI GC showed no significant survival benefit with the addition of CMT.

Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (-)] GC. The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS-STING was highly expressed in dMMR GC compared to pMMR/EBV (-) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8+ tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (-). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment.

Gastric cancer remains a formidable challenge in oncology with high mortality rates and few advancements in treatment. Claudin-18.2 (CLDN18.2) is a tight junction protein primarily expressed in the stomach and is frequently overexpressed in certain subsets of gastric cancers. Targeting CLDN18.2 with monoclonal antibodies, such as zolbetuximab (IMAB362), has shown promising efficacy results in combination with chemotherapy.

The molecular cell biology of CLDN18.2 is discussed along with studies demonstrating the utility of CLDN18.2 expression as a biomarker and therapeutic target. Important clinical studies are reviewed, including Phase III trials, SPOTLIGHT and GLOW, which demonstrate the efficacy of zolbetuximab in combination with chemotherapy in patients with CLDN18.2-positive advanced gastric cancer.

CLDN18.2 is involved in gastric differentiation through maintenance of epithelial barrier function and coordination of signaling pathways, and its expression in gastric cancers reflects a 'gastric differentiation' program. Targeting Claudin-18.2 represents the first gastric cancer specific 'targeted' treatment. Further studies are needed to determine its role within current gastric cancer treatment sequencing, including HER2-targeted therapies and immunotherapies. Management strategies will also be needed to better mitigate zolbetuximab-related treatment side effects, including gastrointestinal (GI) toxicities.

Gastric cancer (GC) is highly metastatic and characterized by HER2 amplification. Aberrant HER2 expression drives metastasis, therapy resistance, and tumor recurrence. HER2 amplification contributes to drug resistance by upregulating DNA repair enzymes and drug afflux proteins, reducing drug efficacy. HER2 modulates transcription factors critical for cancer stem cell properties, further impacting drug resistance. HER2 activity is influenced by HER-family ligands, promoting oncogenic signaling. These features point to HER2 as a targetable driver in GC. This review outlines recent advances in HER2-mediated mechanisms and their upstream and downstream signaling pathways in GC. Additionally, it discusses preclinical research investigation that comprehends trastuzumab-sensitizing phytochemicals, chemotherapeutics, and nanoparticles as adjunct therapies. These developments hold promise for improving outcomes and enhancing the management of HER2-positive GC.

The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancers includes neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgical resection; however, disease-free survival in these patients remains poor. Immune checkpoint inhibitors (ICIs) are approved for adjuvant treatment of locally advanced esophageal and GEJ cancers, but their benefit in the perioperative and neoadjuvant settings remains under investigation.

We used the PubMed online database to conduct a literature search to identify studies that investigated immunotherapy for locally advanced esophageal and GEJ carcinoma. A review of ClinicalTrials.gov yielded a list of ongoing trials.

Adjuvant nivolumab for residual disease after neoadjuvant chemoradiotherapy and surgery is the only approved immunotherapy regimen for locally advanced esophageal cancer. Early-phase trials investigating the addition of neoadjuvant or perioperative ICIs to standard-of-care multimodality approaches have observed pathologic complete response rates as high as 60%. Response rates are highest for ICIs plus chemoradiotherapy for esophageal squamous cell carcinoma and dual checkpoint inhibition in mismatch repair-deficient adenocarcinomas. Safety profiles are acceptable, with a pooled adverse event rate of 27%. Surgical morbidity and mortality with immunotherapy are similar to historical controls with no immunotherapy, and R0 resection rates are high. When reported, disease-free survival among patients treated with perioperative immunotherapy is promising.

Outside of clinical trials, immunotherapy for resectable esophageal carcinoma is limited to the adjuvant setting. Phase III trials investigating neoadjuvant and perioperative immunotherapy are now underway and will provide much-needed data on survival that may ultimately lead to practice-changing recommendations.

We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy).

This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes.

Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5.

Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.

Mismatch repair deficiency (dMMR) is a characteristic feature of cancers linked to Lynch syndrome. However, in most cases, it results from sporadic somatic events rather than hereditary factors. The term 'Lynch-like syndrome' (LLS) has been used to guide colorectal cancer surveillance for relatives of individuals with a dMMR tumour when somatic and germline genomic testing is uninformative. As the assessment of mismatch repair through immunohistochemistry and/or microsatellite instability is increasingly applied across various tumour types for treatment planning, dMMR is increasingly detected in tumours where suspicion of hereditary aetiology is low. Our objective was to establish current practices and develop national guidance for investigating, and managing relatives of, patients with cancers demonstrating unexplained dMMR.

This was achieved through a virtual consensus meeting involving key stakeholders from the UK, through premeeting surveys, structured discussions and in-meeting polling to formulate best practice guidance.

We identified variability in the availability of diagnostic technologies across specialist centres. It was agreed that equitable access to baseline testing is required, acknowledging the need for a pragmatic approach to investigating dMMR cancers not traditionally associated with Lynch syndrome. Factors such as family history, age, tumour type, protein loss pattern and extent of the investigation were deemed crucial in guiding family management. The term 'unexplained dMMR' was recommended over LLS.

Decisions regarding investigations and future cancer risk management in patients and relatives should be nuanced, considering factors like clinical suspicion of hereditary predisposition to allocate limited resources efficiently and avoid unnecessary investigations in low-suspicion families.

The standard of care for patients with operable gastric adenocarcinoma is perioperative chemotherapy and surgical resection. The deficient mismatch repair (dMMR)/microsatellite instability (MSI-H) phenotype is a major predictive biomarker for immune checkpoint inhibitors (ICIs) efficacy in advanced disease. Several phase II and III trials suggest a promising future role of immunotherapy with or without chemotherapy in the neoadjuvant/adjuvant setting, especially in MSI-H localized gastric adenocarcinomas. We present a 38-year-old man diagnosed in March 2022 with poorly differentiated gastric adenocarcinoma clinical stage III (cT4 N0 M0) with deficiency of MLH1 and PMS2, combined positive score (CPS) of 100 and negative HER2 immunohistochemistry, had poor tumor response to preoperative 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT). It was considered unresectable because of the involvement of the colon, mesocolon, duodenum, pancreas, and retroperitoneum. Then, first-line systemic treatment with 5-FU, leucovorin, and oxaliplatin (FOLFOX)-nivolumab was initiated in August 2022, with a significant radiologic tumor reduction after six cycles, allowing a curative surgery in March 2023 with complete pathologic tumor response, followed by capecitabine and nivolumab for one year, maintaining radiological remission in the last follow-up in April 2024. With this case report, we conclude that it is likely that chemoimmunotherapy or immunotherapy alone may be alternative neoadjuvant treatment choices for MSI-H locally advanced gastric cancer patients.

To investigate the value of intratumoral and peritumoral radiomics based on contrast-enhanced computer tomography (CECT) to preoperatively predict microsatellite instability (MSI) status in gastric cancer (GC) patients.

A total of 189 GC patients, including 63 patients with MSI-high (MSI-H) and 126 patients with MSI-low/stable (MSI-L/S), were randomly divided into the training cohort and validation cohort. Intratumoral and 5-mm peritumoral regions' radiomics features were extracted from CECT images. The features were standardized by Z-score, and the Inter- and intraclass correlation coefficient, univariate logistic regression analysis, and least absolute shrinkage and selection operator (LASSO) were applied to select the optimal radiomics features. Radiomics scores (Rad-score) based on intratumoral regions, peritumoral regions, and intratumoral + 5-mm peritumoral regions were calculated by weighting the linear combination of the selected features with their respective coefficients to construct the intratumoral model, peritumoral model, and intratumoral + peritumoral model. Logistic regression was used to establish a combined model by combining clinical characteristics, CT semantic features, and Rad-score of intratumoral and peritumoral regions.

Eleven radiomics features were selected to establish a radiomics intratumoral + peritumoral model. CT-measured tumor length and tumor location were independent risk factors for MSI status. The established combined model obtained the highest area under the receiver operating characteristic (ROC) curve (AUC) of 0.830 (95% CI, 0.727-0.906) in the validation cohort. The calibration curve and decision curve demonstrated its good model fitness and clinical application value.

The combined model based on intratumoral and peritumoral CECT radiomics features and clinical factors can predict the MSI status of GS with moderate accuracy before surgery, which helps formulate personalized treatment strategies.

The aim of the study was to determine DNA mismatch repair (MMR) proteins by immunohistochemically using MLH1, MSH2, MSH6, and PMS2 antibodies in patients diagnosed as pancreatic ductal adenocarcinoma and to assess its relationship with histopathological and clinical prognostic parameters. Fifty cases with a diagnosis of pancreatic ductal adenocarcinoma who underwent surgical resection, were included in the study. Demographic and histopathological features of the patients were collected from the medical records. The relationships between microsatellite status and prognostic parameters were determined. The mean age of the patients was 66.5 ± 9.5 years (range: 47-87) and male/female ratio was 1.63 (31/19). No errors were detected in DNA MMR proteins in any of the cases, and were classified as microsatellite stable. The mean tumor diameter was 4.01 ± 1.77 cm and 74% of the tumors were localized in the pancreatic head. All of the cases had lymphatic invasion, whereas vascular invasion was detected in only 78% and perineural invasion in 98% of the patients. When the relationship between prognostic parameters and survival was evaluated, statistically significant correlation was observed in patient age and histopathological parameters such as tumor diameter, status of surgical margins, and vascular invasion (p < 0.05). Age, tumor size, presence of tumor at surgical margins, vascular invasion, and adjuvant treatment were correlated with survival. Although microsatellite instability was not detected in our cases, it is important to determine the microsatellite status by immunohistochemistry for predicting the chemotherapy response and determining the immunotherapy option in pancreatic adenocarcinomas.

Epstein-Barr virus (EBV) is a pathogen known to cause a number of malignancies, often taking years for them to develop after primary infection. EBV-associated gastric cancer (EBVaGC) is one such malignancy, and is an immunologically, molecularly and pathologically distinct entity from EBV-negative gastric cancer (EBVnGC). In comparison with EBVnGCs, EBVaGCs overexpress a number of immune regulatory genes to help form an immunosuppressive tumor microenvironment (TME), have improved prognosis, and overall have an "immune-hot" phenotype. This review provides an overview of the histopathology, clinical features and clinical outcomes of EBVaGCs. We also summarize the differences between the TMEs of EBVaGCs and EBVnGCs, which includes significant differences in cell composition and immune infiltration. A list of available EBVaGC and EBVnGC gene expression datasets and computational tools are also provided within this review. Finally, an overview is provided of the various chemo- and immuno-therapeutics available in treating gastric cancers (GCs), with a focus on EBVaGCs.

Tumor-infiltrating lymphocytes (TILs) play a regulatory role in the tumor-associated immune response and are important in the prognosis and treatment response of several cancers. However, because of its heterogeneity, the prognostic value of TILs in gastric cancer (GC) is still controversial. Thus, this study aimed to investigate the association between the density of TILs and patients' outcomes in GC.

Patients with gastric adenocarcinoma who underwent curative intent gastrectomy were retrospectively investigated. The groups for analysis were determined on the basis of TIL intensity and percentage of CD3+ T-cell infiltration by immunohistochemical. Furthermore, Epstein-Barr virus (EBV), microsatellite instability (MSI), T-cell ratio of CD4 to CD8, and programmed death protein ligand 1 (PD-L1) status were evaluated.

A total of 345 patients were enrolled: 124 patients with GCs (35.9%) were classified as the low-CD3+ TIL group, and 221 patients with GCs (64.1%) were classified as the high-CD3+ TIL group. Poorly differentiated histology (P = .014), EBV-positive status (P < .001), PD-L1-positive status (P = .001), and CD4 < CD8 (P < .001) were associated with high-CD3+ GC. There was no difference regarding MSI status, the degree of tumor invasion (pT), the presence of lymph node metastasis, and pTNM stage between low- and high-CD3+ groups. In survival analysis, the high-CD3+ group had better disease-free survival and overall survival rates than had the low-CD3+ group (P = .055 and P = .041, respectively). In the multivariate analysis, total gastrectomy, lymph node metastasis, advanced pT stage, and low CD3+ levels were independent factors related to worse survival.

High CD3+ TILs levels were significantly associated with improved survival and could serve as prognostic biomarkers in GC. In addition, CD3+ T-cell infiltration was related to both EBV-positive and PD-L1-positive GC and may assist in the investigation of targets in immunotherapy.

Today, survivin is known as one of the most specific cancer proteins; provide unique and practical study opportunities. Clinical value of survivin in gastric cancer (GC) is not yet appointed. To establish the expression level of survivin and its diagnosis value in Iranian patients with GC, we evaluated the association of survivin expression with clinicopathologic factors.

Overall, 60 matched-normal controls with 60 GC samples including 30 cases with evidence of metastasis at time of our study and 30 cases without evidence of metastasis were recruited, in Tehran, Iran during 2008 to 2018. Survivin expression was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) study.

Increased expression of survivin at mRNA and protein levels was found in 86.7% and 71.6% of cases, respectively. Evidence indicated a significant difference in survivin mRNA expression level between tumor and nontumoral (marginal) tissues (P<0.001). The difference in expression of survivin mRNA was not significant between metastatic and non-metastatic tumor tissues (P=0.171). Positive immunoreactivity of survivin was observed to be predominantly in the nucleus of tumor cells. A significant difference in survivin protein expression was detected between tumor and non-tumoral tissues (P<0.001) and between metastatic and non-metastatic tumor tissues (P<0.001). There was no significant association between survivin mRNA expression and clinicopathological variables. However, survivin protein expression was significantly correlated with perineural involvement (P<0.018).

This data could be supportive of using survivin as a useful diagnostic marker in GC. Although, more research is needed in this area.

Microsatellite instability-high (MSI-H) has gained considerable interests since it was approved as a tumor-agnostic biomarker in immunotherapy. However, the reported characteristics of MSI-H gastric cancer (GC) are inconsistent due to the biological complexity. Here, we aim to clarify the prevalence, risk factors, clinicopathological/molecular features and outcomes of MSI-H GC though a comprehensive review on 43246 patients from 134 cohorts. Overall, the proportion of MSI-H GC was 14.5% (95% CI, 13.3%-15.8%). Patients with MSI-H GC were less likely to have Epstein-Barr virus infection. High incidences of MSI-H GC were associated with female, older age, lower gastric body, Lauren intestinal histology, WHO tubular and mucinous subtypes, and early disease stage. Additionally, patients with MSI-H GC harbored more KRAS mutation, PD-L1 positivity, CD8 overexpression, and higher TMB, but less HER2 positivity and TP53 mutation. When treated with conventional strategy, the 5-year survival rates in MSI-H patients (70.3%) and MSI-L/MSS patients (43.7%) were significantly different (p<0.001). Patients with MSI-H GC derived larger benefit from immunotherapy in term of overall survival (pInteraction<0.001) and objective response (pInteraction=0.02). Since the prevalence of MSI-H GC is relatively high and associated with distinct clinicopathological and molecular characteristics, MSI testing should be conducted during standard diagnostical activity. Moreover, giving MSI-H tumors are often diagnosed at early stage and have favorable outcomes, less aggressive treatment strategies may be considered in clinical practice. In summary, this panoramic review may assist in design and/or interpretation of clinical trials, provide references in drug development, and constitute complementary information in drafting the clinical practice guideline.

In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

Gastric cancer is a prevalent type of tumor with a poor prognosis. Given the high occurrence of genomic instability in gastric cancer, it is essential to investigate the prognostic significance of genes associated with genomic instability in this disease.

We identified genomic instability-related lncRNAs (GInLncRNAs) by analyzing somatic mutation and transcriptome profiles. We evaluated co-expression and enrichment using various analyses, including univariate COX analysis and LASSO regression. Based on these findings, we established an lncRNA signature associated with genomic instability, which we subsequently assessed for prognostic value, immune cell and checkpoint analysis, drug sensitivity, and external validation. Finally, PCR assay was used to verify the expression of key lncRNAs.

Our study resulted in the establishment of a seven-lncRNA prognostic signature, including PTENP1-AS, LINC00163, RP11-169F17.1, C8ORF87, RP11-389G6.3, LINCO1210, and RP11-115H13.1. This signature exhibited independent prognostic value and was associated with specific immune cells and checkpoints in gastric cancer. Additionally, the model was correlated with somatic mutation and several chemotherapeutic drugs. We further confirmed the prognostic value of LINC00163, which was included in our model, in an independent dataset. Our model demonstrated superior performance compared to other models. PCR showed that LINC00163 was significantly up-regulated in 4 adjacent normal tissues compared with the GC tissues.

Our study resulted in the establishment of a seven-lncRNA signature associated with genomic instability, which demonstrated robust prognostic value in predicting the prognosis of gastric cancer. The signature also identified potential chemotherapeutic drugs, making it a valuable tool for clinical decision-making and medication use.

Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p‑value of 0.0015) and lower lymph node involvement (p‑value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managing these innovative aspects of GC. This study aims to present an in-depth and comprehensive review of the clinical advancements in targeted therapy and immunotherapy for advanced GC.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. Current treatments mainly rely on surgery- and chemotherapy-based systemic; however, the prognosis remains poor for advanced disease. Recent studies have suggested that immunotherapy has significant potential in cancer therapy; thus, GC immunotherapy may improve quality of life and survival for patients with this disease.

To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.

We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database. We analyzed 2013 pub-lications from 1999 to February 1, 2023, using the VOSviewer and CiteSpace software. We assessed publication and citation distributions using the WoS platform and explored research countries, institutions, journals, authors, references, and keywords (co-occurrence, timeline view, and burst analysis). In addition, we examined 228 trials on immunotherapy, 137 on adoptive cell therapy, 274 on immune checkpoint inhibitors (ICIs), and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform. The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis (RCA) are presented.

Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years. China accounted for almost half the publications, followed by the United States. The number of publications in recent years has been growing continuously, and most institutions and authors with the most publications are from China. The main keywords or clusters identified were "tumor microenvironment", "adoptive immunotherapy", "dendritic therapy", and "microsatellite instability".

Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years. Considerable progress has been made in vaccinations, immune checkpoint therapy, and adoptive cellular therapy. In particular, ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC. We suggest that the combination of ICIs, chemotherapy, targeted therapy, and other immunotherapies should be the primary research direction in the future.

Gastric cancer (GC) is a common malignant tumor of the digestive system. Disulfidptosis is a new programmed cell death mechanism, although its specific mechanism in GC is incompletely understood.

In this study, we used bioinformatics analysis to explore a disulfidptosis-based predictive model related to GC prognosis and to identify potential therapeutic targets and sensitive drugs for GC.

We extracted GC-related data from The Cancer Genome Atlas and Gene Expression Omnibus databases. R software (version 4.2.1) was used for correlation analysis.

Through the above analysis, we found that the disulfidptosis related gene may be related to the prognosis of GC. Six genes, namely, PLS3, GRP, APOD, SGCE, COL8A1, and VAMP7, were found to constitute a predictive model for GC prognosis. APOD is a potential therapeutic target for treating GC. Bosutinib and other drugs are sensitive for the treatment of GC.

The results of this study indicate that disulfidptosis is related to the prognosis and treatment of GC, while APOD represents a potential therapeutic target for GC.