Treatment Of Gastric Cancer Patients Research Articles

TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21

GC (Gastric cancer) is one of the most common malignant tumours, with over 95% of gastric cancer patients being adenocarcinoma and most gastric cancer patients having no apparent symptoms in the early stages. Finding biomarkers for early screening of gastric cancer and exploring new targets for gastric cancer treatment are urgent problems to be solved in the treatment of gastric cancer, with significant clinical outcomes for the survival rate of gastric cancer patients. The AAA+ family ATPase thyroid hormone receptor-interacting protein 13 (TRIP13) has been reported to play an essential role in developing various tumours. However, the biological function and molecular mechanism of TRIP13 in gastric cancer remain unclear. This study confirms that TRIP13 is highly expressed in gastric cancer tissue samples and that TRIP13 participates in the proliferation, migration, invasion in vitro, and tumourigenesis and metastasis in vivo of gastric cancer cells. Mechanistically, this study confirms that TRIP13 directly interacts with DDX21 and stabilises its expression by restraining its ubiquitination degradation, thereby promoting gastric cancer progression. Additionally, histone deacetylase 1 (HDAC1) is an upstream factor of TRIP13, which could target the TRIP13 promoter region to promote the proliferation, migration, and invasion of gastric cancer cells. These results indicate that TRIP13 serve is a promising biomarker for the treating of gastric cancer patients, and the HDAC1-TRIP13/DDX21 axis might provide a solid theoretical basis for clinical treatment of gastric cancer patients.

Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients.

Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients. However, few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators. To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients. From October 2018 to April 2020, a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study. The relationship between serum tumor markers and clinical and pathological data were analyzed. We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis. Overall survival (OS) was also compared across different stages of gastric cancer. The deadline for follow-up was May 31, 2023. A total of 1236 patients were included in our study. Univariate analysis found that age, clinical stage, T and N stage, tumor location, differentiation, Borrmann type, size, and four serum tumor markers were prognostic factors of OS (P < 0.05). It was shown that clinical stage, tumor size, alpha foetoprotein, carcinoembryonic antigen, CA125 and CA19-9 (P < 0.05) were independent prognostic factors for OS. According to the scoring results obtained from the statistical model, we found that patients with high scores had poorer survival time (P < 0.05). Furthermore, in stage I patients, the 3-year OS for scores 0-3 ranged from 96.85%, 95%, 85%, and 80%. In stage II patients, the 3-year OS for scores 0-4 were 88.6%, 76.5%, 90.5%, 65.5% and 60%. For stage III patients, 3-year OS for scores 0-6 were 70.9%, 68.3%, 64.1%, 50.9%, 38.4%, 18.5% and 5.2%. We also analyzed the mean survival of patients with different scores. For stage I patients, the mean OS was 55.980 months. In stage II, the mean OS was 51.550 months. The mean OS for stage III was 39.422 months. Our statistical model can effectively predict the prognosis of gastric cancer patients.

Evaluating effectiveness and safety of combined percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy in acute cholecystitis patients: Meta-analysis.

Acute cholecystitis (AC) is a common disease in general surgery. Laparoscopic cholecystectomy (LC) is widely recognized as the "gold standard" surgical procedure for treating AC. For low-risk patients without complications, LC is the recommended treatment plan, but there is still controversy regarding the treatment strategy for moderate AC patients, which relies more on the surgeon's experience and the medical platform of the visiting unit. Percutaneous transhepatic gallbladder puncture drainage (PTGBD) can effectively alleviate gallbladder inflammation, reduce gallbladder wall edema and adhesion around the gallbladder, and create a "time window" for elective surgery. To compare the clinical efficacy and safety of LC or PTGBD combined with LC for treating AC patients, providing a theoretical basis for choosing reasonable surgical methods for AC patients. In this study, we conducted a clinical investigation regarding the combined use of PTGBD tubes for the treatment of gastric cancer patients with AC. We performed searches in the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database. The search encompassed literature published from the inception of these databases to the present. Subsequently, relevant data were extracted, and a meta-analysis was conducted using RevMan 5.3 software. A comprehensive analysis was conducted, encompassing 24 studies involving a total of 2564 patients. These patients were categorized into two groups: 1371 in the LC group and 1193 in the PTGBD + LC group. The outcomes of the meta-analysis revealed noteworthy disparities between the PTGBD + LC group and the LC group in multiple dimensions: (1) Operative time: Mean difference (MD) = 17.51, 95%CI: 9.53-25.49, P < 0.01; (2) Conversion to open surgery rate: Odds ratio (OR) = 2.95, 95%CI: 1.90-4.58, P < 0.01; (3) Intraoperative bleeding loss: MD = 32.27, 95%CI: 23.03-41.50, P < 0.01; (4) Postoperative hospital stay: MD = 1.44, 95%CI: 0.14-2.73, P = 0.03; (5) Overall postoperative complication rate: OR = 1.88, 95%CI: 1.45-2.43, P < 0.01; (6) Bile duct injury: OR = 2.17, 95%CI: 1.30-3.64, P = 0.003; (7) Intra-abdominal hemorrhage: OR = 2.45, 95%CI: 1.06-5.64, P = 0.004; and (8) Wound infection: OR = 0. These findings consistently favored the PTGBD + LC group over the LC group. There were no significant differences in the total duration of hospitalization [MD = -1.85, 95%CI: -4.86-1.16, P = 0.23] or bile leakage [OR = 1.33, 95%CI: 0.81-2.18, P = 0.26] between the two groups. The combination of PTGBD tubes with LC for AC treatment demonstrated superior clinical efficacy and enhanced safety, suggesting its broader application value in clinical practice.

Present situation of minimally invasive surgical treatment for early gastric cancer.

Minimally invasive surgery is a kind of surgical operation, which is performed by using professional surgical instruments and equipment to inactivate, resect, repair or reconstruct the pathological changes, deformities and wounds in human body through micro-trauma or micro-approach, in order to achieve the goal of treatment, its surgical effect is equivalent to the traditional open surgery, while avoiding the morbidity of conventional surgical wounds. In addition, it also has the advantages of less trauma, less blood loss during operation, less psychological burden and quick recovery on patients, and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients. Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer (EGC): endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR), endoscopic submucosal excavation (ESE), submucosal tunnel endoscopic resection), laparoscopic and endoscopic cooperative surgery (LECS); Among them, EMR, EFTR and LECS technologies have a wide range of applications and different modifications have been derived from their respective surgical operations, such as band-assisted EMR (BA-EMR), conventional EMR (CEMR), over-the-scope clip-assisted EFTR, no-touch EFTR, the inverted LECS, closed LECS, and so on. These new and improved minimally invasive surgeries are more precise, specific and effective in treating different types of EGC.

Abstract CT069: Targeting EpCAM via CAR T-cells is an effective treatment for gastric cancer patients and subsequent toll-like receptor signaling activation in CD36+ monocyte underlies the resulting cytokine release syndrome

Abstract EpCAM is highly expressed in various cancer types of the gastrointestinal system and at metastatic sites. It serves as a promising prognostic marker and therapeutic target. We conducted a first-in-human, open-label, single-arm, multicenter, phase 1 clinical trial following the classical "3+3" dose escalation design. The endpoints of this clinical trial are to assess the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic (PD) profile of EpCAM CAR-T. The trial is still ongoing, and our interim analysis results revealed a favorable safety profile of EpCAM CAR-T. No treatment-related deaths were observed within the 4-week follow-up period after infusion. 2 (12.5%) patients in high dose group (3*106) experienced dose-limiting toxicity (DLT) and 8 (50%) patients experienced grade 1-3 CRS. EpCAM CAR-T showed promising efficacy in gastric cancer. In gastric cancer group, the overall response rate (ORR) and disease control rate (DCR) reached 20.0% and 90.0%, respectively. However, the efficacy of EpCAM CAR-T in treating colorectal cancer was suboptimal, with an objective response rate (ORR) of 0% and disease control rate (DCR) of 50%. In our study, we observed that patients in gastric cancer (GC) group who developed cytokine release syndrome (CRS) had a weak response to CAR-T cell therapy, which is consistent with previous observations in animal models. We employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from GC group patients receiving EpCAM CAR-T treatment to explore the potential antagonism between CRS and treatment efficacy. Our findings underscore the significant role of monocytes in the regulation of CRS and treatment response. Specifically, we identified an increased abundance of Toll-like receptor (TLR)-dependent CD36+ monocytes in non-responders experiencing CRS. In a mouse model, we demonstrated that blocking TLR signaling in monocytes attenuated CRS induced by EpCAM CAR-T cells. Conversely, CD16+ monocytes were enriched in responders, displaying upregulated antigen presentation pathways and enhanced tumor infiltration capacity. In vivo, experiments revealed that blocking the antigen presentation pathway or inhibiting tumor infiltration of CD16+ monocytes resulted in reduced anti-tumor response of EpCAM CAR-T cells. Our findings highlight the critical role of intrinsic monocyte subpopulations as determinants of CAR-T efficacy and CRS. These insights may provide valuable strategies for predicting and enhancing the safety and efficacy of CAR-T cell therapy for solid tumors. Citation Format: TIanhang Luo, Zhengmao Lu, Zhongen Wu, Yuxuan Dong, Yuanyuan Zhu, Mei Feng, Shenglin Mei, Weijia Fang, Di Zhu. Targeting EpCAM via CAR T-cells is an effective treatment for gastric cancer patients and subsequent toll-like receptor signaling activation in CD36+ monocyte underlies the resulting cytokine release syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT069.

Effect of Epstein-Barr Virus Infection on the Treatment of Gastric Cancer in Tumor Immunotherapy

Gastric cancer is one of the biggest medical problems in the world today, and it is also a huge medical challenge for human beings. The main challenge is the complexity of the limitations of gastric cancer itself. At present, the efficacy of single-drug immune checkpoint inhibitors in treatment is not clear. It can be found in previous cases that Epstein-Barr virus positive gastric cancer patients have significantly higher response to PD-1 antibodies than the overall patients, from which it can be found that EBV infection can play an important role in gastric cancer immunotherapy. The purpose of this study was to investigate the effect of Epstein-Barr virus infection on gastric cancer and analyze specific clinical cases. The results showed that patients infected with Epstein-Barr virus had obvious advantages in the treatment of gastric cancer, which was significantly correlated with the expression of PD-L1 and EBV (+). This study highlights the potential benefits of Epstein-Barr virus infection in the treatment of gastric cancer, providing new insights into the development of future immunotherapy strategies. These findings will help to improve the treatment of gastric cancer patients, as well as to better understand the immune properties of gastric cancer and develop related vaccines. The significance of this study is that it provides a solid foundation for innovation in the treatment of gastric cancer.

Abstract 6410: An exosomal microRNA signature predicts the efficacy of ramucirumab plus paclitaxel in advanced gastric cancer: Findings from the prospective IVY trial

Abstract Purpose: With rapid advances in the development of effective therapeutic regimens in patients with advanced gastric cancer, it is imperative to establish individualized treatment approaches that can help identify patient subsets that have the highest likelihood of response to a specific regimen. Although ramucirumab plus paclitaxel therapy is the standard second-line treatment for patients with advanced gastric cancer, biomarkers that can help predict therapeutic response are still lacking. This longitudinal study aimed to establish a liquid-biopsy assay that can predict response to ramucirumab plus paclitaxel therapy in patients with advanced gastric cancer. Experimental Design: A prospective observational multicenter study (named the IVY study) enrolled 115 patients who received ramucirumab plus paclitaxel treatment. We collected serum specimens prior to the initiation of the treatment regimen. Patients were divided into responders and non-responders according to the response evaluation criteria in solid tumors (RECIST). We performed small RNA-sequencing (sRNA-Seq) in a subset of 28 patients with and without response to identify exosomal microRNA-based biomarkers that allowed risk stratification and response prediction in patients with advanced gastric cancer. Results: The sRNA-Seq analysis and rigorous bioinformatic approaches using machine-learning algorithms allowed us to identify a panel of 10 exosomal microRNAs that robustly predicted resistance to ramucirumab plus paclitaxel treatment (AUC: 0.83). The panel of exosomal miRNAs was also shown to have a robust prognostic value for predicting survival outcomes in gastric cancer patients treated with ramucirumab plus paclitaxel, and Cox proportional hazards regression analysis showed that patients classified as high risk on the panel of exosomal miRNAs independent poor prognostic factor (OS: HR = 2.74, 95% CI = 1.56-4.81, P &amp;lt; 0.01, RFS: HR = 1.84, 95% CI = 1.16-2.92, P &amp;lt; 0.01). Following logistic regression and backward elimination, we trained a clinically feasible 5 exosomal miRNA signature by combining it with the Body Mass Index data, an independent clinical predictor (AUC: 0.84). We subsequently successfully validated the performance of this signature in the prospective clinical trial cohort (AUC: 0.87). Finally, we established a prognostic risk nomogram based on the circulating exosomal miRNA signature for a non-invasive and personalized pre-therapeutic selection approach. Conclusions: We have developed a novel liquid biopsy-based assay that allows robust prediction of response to ramucirumab plus paclitaxel treatment in gastric cancer patients, and our assay provides a framework for a personalized medicine approach that can provide risk-based management and treatment for each patient prior to the initiation of therapy. Citation Format: Katsutoshi Shoda, Caiming Xu, Yoh Asahii, Takeshi Nagasaka, Daisuke Ichikawa, Ajay Goel. An exosomal microRNA signature predicts the efficacy of ramucirumab plus paclitaxel in advanced gastric cancer: Findings from the prospective IVY trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6410.

Radical gastrectomy is safe for treatment of gastric cancer patients on immunosuppressive drugs after organ transplantation.

De novo malignancies are major causes of death after organ transplantation because the recipients subsequently receive immunosuppressant drugs. When gastric cancer develops, the clinical course of the tumor may be particularly aggressive. However, there are few reliable studies of gastric cancer treatment after organ transplantation. This study examined the clinicopathological characteristics of gastric cancer patients after organ transplantation and evaluated treatment outcomes after gastrectomy. Clinical data were collected from 54 patients who were diagnosed with gastric cancer after organ transplantation. Of these, 30 who underwent surgery for gastric cancer while on immunosuppressant medications were compared with a control group of 625 gastric cancer patients. To compensate for clinical differences between the two groups, 1:1 propensity-score matching was performed. Among the 30 gastric cancer patients on immunosuppressants, kidney transplantation was the most common procedure (19/30, 63.3%) followed by bone marrow (6) and liver transplantation (4); among all 54 patients, 45 were on one or two immunosuppressants. Up-migration to an advanced pathological stage was more frequent in the transplant group. In multivariate analysis, transplantation was a significant risk factor for up-migration from the T, M, and final stages after surgery. When the 30 patients on immunosuppressants who underwent gastric cancer surgery were compared with the matched controls, the total incidence (30.0 vs 40.0%, P = 0.417) and the number of severe postoperative complications (16.7 vs 13.4%, P = 0.417) did not differ significantly between groups after propensity score matching. In terms of overall survival, the transplant group showed significantly worse prognosis in stages I, II, and IV (P < 0.001, P = 0.039 and 0.007, respectively). Radical gastrectomy can be a safe oncological procedure for gastric cancer patients on immunosuppressants after transplantation. Considering their immunosuppressed condition and the possibility of underestimation of the stage of gastric cancer, early detection with endoscopic screening is needed to allow curative treatment.

Construction and validation of prognostic signatures related to mitochondria and macrophage polarization in gastric cancer.

Increasing evidence reveals the involvement of mitochondria and macrophage polarisation in tumourigenesis and progression. This study aimed to establish mitochondria and macrophage polarisation-associated molecular signatures to predict prognosis in gastric cancer (GC) by single-cell and transcriptional data. Initially, candidate genes associated with mitochondria and macrophage polarisation were identified by differential expression analysis and weighted gene co-expression network analysis. Subsequently, candidate genes were incorporated in univariateCox analysis and LASSO to acquire prognostic genes in GC, and risk model was created. Furthermore, independent prognostic indicators were screened by combining risk score with clinical characteristics, and a nomogram was created to forecast survival in GC patients. Further, in single-cell data analysis, cell clusters and cell subpopulations were yielded, followed by the completion of pseudo-time analysis. Furthermore, a more comprehensive immunological analysis was executed to uncover the relationship between GC and immunological characteristics. Ultimately, expression level of prognostic genes was validated through public datasets and qRT-PCR. A risk model including six prognostic genes (GPX3, GJA1, VCAN, RGS2, LOX, and CTHRC1) associated with mitochondria and macrophage polarisation was developed, which was efficient in forecasting the survival of GC patients. The GC patients were categorized into high-/low-risk subgroups in accordance with median risk score, with the high-risk subgroup having lower survival rates. Afterwards, a nomogram incorporating risk score and age was generated, and it had significant predictive value for predicting GC survival with higher predictive accuracy than risk model. Immunological analyses revealed showed higher levels of M2 macrophage infiltration in high-risk subgroup and the strongest positive correlation between risk score and M2 macrophages. Besides, further analyses demonstrated a better outcome for immunotherapy in low-risk patients. In single-cell and pseudo-time analyses, stromal cells were identified as key cells, and a relatively complete developmental trajectory existed for stromal C1 in three subclasses. Ultimately, expression analysis revealed that the expression trend of RGS2, GJA1, GPX3, and VCAN was consistent with the results of the TCGA-GC dataset. Our findings demonstrated that a novel prognostic model constructed in accordance with six prognostic genes might facilitate the improvement of personalised prognosis and treatment of GC patients.

Identification of three lncRNA-related prognostic signatures in gastric cancer by integrated multi-omics analysis.

Aims: The systematic identification of molecular features correlated with the clinical status of gastric cancer (GC) inpatients is significant, although such investigation remains insufficient. Methods: GC subtyping based on RNA sequencing, copy number variation and DNA methylation data were derived from The Cancer Genome Atlasprogram. Prognostics lncRNA biomarkers for GC were identified by univariate Cox, LASSO and SVM-RFE analysis. Results: Three molecular subtypes with significant survival discrepancies, and their specific DEmRNAs and DElncRNAs were identified. Three reliable prognostic-associated lncRNA, including LINC00670, LINC00452 and LINC00160, were selected for GC. Conclusion: Our findings expanded the understanding on the regulatory network of lncRNAs in GC, providing potential targets for prognosis and treatment of GC patients.

Integrated RNA-sequencing and network analysis approach to identify the Hub genes and vital pathways associated with gastric cancer

Context: Gastric cancer is one of the most prevalent types of cancer in developing countries and ranks fourth in terms of death causes. Helicobacter pylori infection is a significant contributor to the emergence of gastric cancer. Lack of early diagnosis of gastric cancer is a leading cause of death. Aims: To identify the key genes and pathways involved in gastric cancer. Methods: This study performed a comprehensive analysis of RNA-Seq data from human gastric cancer and adjacent normal tissues. Raw data passed quality checks with FastQC and were aligned to GRCh38 using HISAT2. Subread's FeatureCounts handled transcript assembly and quantification. DESeq2 pinpointed significant genes, while ClueGO explored gene ontology and KEGG pathways. Protein-protein interaction networks, constructed with StringApp, aided in identifying hub genes through CytoHubba. This holistic approach yields insights into the molecular mechanisms underpinning gastric cancer. Results: This study detected 711 differentially expressed genes (DEGs) between normal and gastric samples. A total of 594 genes were identified as upregulated and 117 as downregulated. Major DEGs are enriched in signal transduction, stimulus-response regulation, transmembrane signaling receptor activity, and signal transduction pathways involving cytokines. In addition, 20 hub genes from the PPI network were identified based on MCC rank analysis from the CytoHubba plugin, contributing to the progression of gastric cancer. Conclusions: The top six hub genes, CD4, CTLA4, CD28, CD80, CD27, and SELL, are expected to regulate several pathways and may serve as potential biomarkers for the early detection and treatment of gastric cancer patients.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in combination with FOLFOX chemotherapy as a first-line treatment for gastric cancer patients with peritoneal metastases: single-arm phase II study

BackgroundGastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment.MethodsThis study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6–7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228–47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity.DiscussionThis study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM.Trial registrationNCT05644249. Registered on December 9, 2022.

METTL3 promotes drug resistance to oxaliplatin in gastric cancer cells through DNA repair pathway.

Gastric cancer (GC) poses a significant threat to human health and remains a prevalent form of cancer. Despite clinical treatments, the prognosis for Gastric cancer patients is still unsatisfactory, largely due to the development of multidrug resistance. Oxaliplatin (OXA), a second-generation platinum drug, is commonly recommended for adjuvant and palliative chemotherapy in Gastric cancer; however, the underlying mechanisms of acquired resistance to Oxaliplatin in Gastric cancer patients are not yet fully understood. In this study, we aimed to explore the potential mechanisms of Oxaliplatin resistance in Gastric cancer by employing bioinformatics analysis and conducting in vitro experiments. Specifically, we focused on investigating the role of methyltransferase-like 3 (METTL3). Our findings revealed that the knockdown of METTL3 significantly impeded the proliferation and migration of Gastric cancer cells. METTL3 knockdown induced apoptosis in OXA-resistant Gastric cancer cells and enhanced their sensitivity to Oxaliplatin. Furthermore, we found that DNA repair pathways were significantly activated in OXA-resistant Gastric cancer cells, and METTL3 knockdown significantly inhibited DNA repair pathways. Another important finding is that METTL3 knockdown and OXA-induced Gastric cancer cell death are additive, and the targeted METTL3 can assist Oxaliplatin treatment. Collectively, our findings suggest that METTL3 knockdown can augment the sensitivity of Gastric cancer cells to Oxaliplatin by impeding DNA repair processes. Consequently, targeting METTL3 holds great promise as a viable adjuvant strategy in the treatment of Gastric cancer patients.

Current opportunities for combined treatment of gastric cancer patients with peritoneal carcinomatosis

Patients with locally advanced gastric cancer are at high risk of peritoneal dissemination. Poor prognosis after surgical treatment is mostly associated with presence of free tumor cells in peritoneal cavity that were not identified during pre-surgery examination. Staging laparoscopy and peritoneal washing with cytological examination are now routinely used to detect peritoneal carcinomatosis and for an accurate cancer staging.Yet there is no standard treatment for patients with morphologically confirmed peritoneal dissemination of gastric origin. International oncological associations such as NCCN, ESMO and AJCC identify presence of free tumor cells in peritoneal cavity as distant metastasis where palliative chemotherapy is recommended as the only treatment option. Literature review shows that even if complete regression of micrometastases is achieved after chemotherapy alone, survival rate of this group of patients remains poor.Today some authors prove combined treatment strategies for patients with peritoneal micrometastases of gastric origin to be effective. Because of the limited number of patients included in these studies there is no specific combined treatment scheme that can be recommended as a standard protocol of treatment patients with advanced gastric cancer.

Comprehensive analysis of anoikis-related genes in prognosis and immune infiltration of gastric cancer based on bulk and single-cell RNA sequencing data.

Accumulating evidence suggests that anoikis resistance is a key process in cancer cell metastasis, making it an attractive therapeutic target. Therefore, anoikis may become a new treatment for gastric cancer. We used the univariate Cox regression method to screen gastric cancer-related anoikis genes, and a prognostic risk model was established. We analyzed differences between high- and low-risk groups in terms of tumor infiltrating immune cells, gene mutation signatures, and treatment of gastric cancer. Analysis of model associated genes at single-cell resolution was performed. We filtered to 12 anoikis-related genes and built a prognostic risk model using seven of them, which performed well in multiple datasets. Patients with CCDC178 mutations had a worse prognosis. We also found that patients at low risk were more likely to benefit from chemotherapy and immunotherapy. ERBB2 was found to be highly expressed in epithelial cells and fibroblasts. Our analysis also indicated that gastric cancer samples with high infiltration of iCAFs had a worse prognosis. Seven anoikis-related genes were selected to establish a risk model. The model can be used to predict the prognosis of patients and guide the drug treatment, which provides a new idea for the evaluation and treatment of gastric cancer patients.

Gastric Cancer with Sarcopenia: an Area Worth Focusing On.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer death worldwide, which seriously endangers human health. A number of studies have shown that sarcopenia occurs more frequently in patients with gastric cancer than in the general population and can significantly affect the disease status and survival of patients, which is of great significance in predicting the prognosis of gastric cancer. Patients with gastric cancer may suffer sarcopenia no matter before or after surgery, and the pathogenesis is complex. Abnormal nutrient metabolism and reduced exercise are the leading causes. In addition, surgical treatment and chemotherapy for gastric cancer might participate in the physiological and pathological mechanism of sarcopenia. Generally speaking, exercise and nutritional therapy are the main prevention and treatment methods for sarcopenia. But more prospective evidence is needed to establish reasonable interventions, and other drug treatments are in their infancy. For the diagnostic criteria of sarcopenia, the cut-off values of the skeletal muscle mass index obtained from CT images vary widely and need to be standardized and unified. We also need to explore simple predictors to facilitate sarcopenia risk assessment. More research is needed to formulate more appropriate treatments for gastric cancer patients with sarcopenia.

Th1 cells inducing IFNγ response improves immunotherapy efficacy in gastric cancer.

Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment. We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1 (PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis (ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma (IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator (LASSO) analysis. Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ response-related genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis. Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.

Mechanism and Therapeutic Value of Exosomes in Gastric Cancer

<i>Background</i> Gastric cancer is a common gastrointestinal tumor with a high incidence and mortality rate, which is a serious threat to life and health; therefore, early diagnosis and interventions are particularly important. Currently, emerging gastric cancer-related targets Exosomes (EXOs) are being explored, (EXOs) are various bioactive substances, such as proteins, nucleic acids and lipids, actively secreted by various cells. It has been shown that exosomes are extensively involved in substance exchange and signal transduction between gastric cancer cells, affecting tumor proliferation and metastasis. Exosomes are biomarkers for the diagnosis and prognosis of gastric cancer, and are one of the hot spots in cancer research. <i>Objective</i> This paper mainly summarizes the research progress of related exosome detection methods and condenses a large amount of research evidence to systematically describe the characteristics of exosomes, related mechanisms and their diagnostic and therapeutic values in gastric cancer, hoping to provide new ideas and methods for the diagnosis and treatment of gastric cancer and new opportunities for better treatment of gastric cancer patients. <i>Method</i> Through extensive reading of relevant literature, we highly summarize relevant research mechanisms and diagnostic and therapeutic values, and explore and summarize the latest hot spots. <i>Result and Conclusion</i> EXOs as an emerging research hotspot, have extensive clinical value in gastric cancer progression. Using EXOs as key targets can provide new ideas and directions for the precise diagnosis and treatment of related GI tract tumors. It is also beneficial to the early diagnosis and of gastric cancer, and provides certain research prospects for the study of related inhibitory drugs.

The impact of COVID-19 for postoperative outcomes using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer.

The coronavirus disease 2019 (COVID-19) pandemic had resulted in either failure to provide required medical resources or delayed treatment for gastric cancer patients. This study aimed to investigate the impact of COVID-19 on the incidence of postoperative complications using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer. We collected the data of patients who underwent distal gastrectomy from January 2018 to December 2021 from the National Clinical Database (NCD), a web-based surgical registration system in Japan. The number of surgical cases, the use of intensive care units, and the incidence of morbidity per month were analyzed. We also calculated the standardized mortality ratio (SMR), defined as the ratio of the number of observed patients to the expected number of patients calculated using the risk calculator established in the NCD, for several morbidities, including pneumonia, sepsis, 30-day mortality, and surgical mortality. A decrease of 568 gastrectomies was observed from April 2020 to May 2020. Although the absolute number of patients admitted to intensive care units had declined since 2020, the proportion of patients admitted to the ICU did not change before and after the pandemic. Mortality and critical morbidity (such as pneumonia and sepsis) rates were not worse during the pandemic compared to pre-pandemic periods per the SMR. Surgical management was conducted adequately through the organized efforts of the entire surgery department in our country even in a pandemic during which medical resources and staff may have been limited.

Systematic review and meta-analysis comparing proximal gastrectomy with double-tract-reconstruction and total gastrectomy in gastric and gastroesophageal junction cancer patients: Still no sufficient evidence for clinical decision-making.

To compare proximal gastrectomy with double-tract reconstruction and total gastrectomy in patients with gastroesophageal junction (AEG II-III) and gastric cancer. We conducted systematic searches in Medline, Web of Science, and Cochrane Library until December 20, 2021 (PROSPERO registration number: CRD42021291500). Risk of bias was assessed using the revised Cochrane risk of bias tool and the ROBINS-I tool, as applicable. Evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. One randomized controlled trial (RCT) and 13 non-RCTs with 1,317 patients (715 patients with total gastrectomy and 602 patients with proximal gastrectomy with double-tract reconstruction) were included. Patients treated by total gastrectomy had a significantly higher proportion of advanced cancer stages International Union Against Cancer IB-III (odds ratio: 0.68, 95% confidence interval: 0.51-0.91, P= .01). This heterogeneity biases the observed improved overall survival of patients after proximal gastrectomy with double-tract reconstruction (odds ratio: 0.67, 95% confidence interval: 0.44-1.01, P= .05). Both procedures were comparably efficient regarding perioperative parameters. Postoperative/preoperative bodyweight ratio (mean difference: 3.56, 95% confidence interval: 1.32-5.79, P= .002), postoperative/preoperative serum-hemoglobin ratio (mean difference 3.73, 95% confidence interval: 1.59-5.88, P < .001), and postoperative serum vitamin B12 levels (mean difference 42.46, 95% confidence interval: 6.37-78.55, P= .02) were superior after proximal gastrectomy with double-tract reconstruction, while postoperative/preoperative serum-albumin ratio (mean difference 1.24, 95% confidence interval: -4.76 to 7.24, P= .69) and postoperative/preoperative serum total protein ratio (mean difference 1.12, 95% confidence interval: -2.77 to 5.00, P= .57) were not different. Health-related quality of life data were reported in only 2 studies, which found no significant advantages for proximal gastrectomy with double-tract reconstruction. Proximal gastrectomy with double-tract reconstruction offers advantages in postoperative nutritional parameters compared to total gastrectomy (GRADE: moderate quality of evidence). Oncological effectiveness of proximal gastrectomy with double-tract reconstruction cannot be assessed (GRADE: very low quality of evidence). Further thoroughly planned randomized controlled trials in Western patient cohorts are necessary to improve treatment for gastric cancer patients.