Gastric Cancer最新文献

Background: This study assessed the impact of an institutional certification system that was newly introduced by the Japanese Gastric Cancer Association on short-term surgical outcomes in patients with gastric cancer using data from the National Clinical Database.

Methods: A retrospective cohort study of distal gastrectomy and total gastrectomy procedures performed between January 2020 and December 2022 was conducted. The institutions were classified into three categories: type A, type B, and non-certified institutions, in decreasing order of certification stringency. The primary outcome was the incidence of grade ≥ IIIa postoperative complications based on the Clavien-Dindo classification system. The secondary outcome was surgery-related mortality. Logistic regression with risk adjustment, estimated using generalized estimating equations, was used to account for intra-cluster correlation.

Results: There was no significant difference in the risks of distal gastrectomy-related complications across the three institution types. However, type A- (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.31-0.49) and type B-certified institutions (OR 0.59, 95% CI 0.49-0.71) had a significantly lower mortality risk than non-certified ones. On the other hand, Type A- (OR 1.25, 95% CI 1.09-1.44) and type B-certified institutions (OR 1.17, 95% CI 1.03-1.33) had higher risks of postoperative total gastrectomy-related complications than non-certified ones. Nevertheless, type A- (OR 0.41, 95% CI 0.29-0.58) and type B-certified institutions (OR 0.67, 95% CI 0.51-0.88) had significantly lower surgery-related mortality risks than non-certified ones.

Conclusions: Certified institutions demonstrated lower surgical mortality risks, highlighting the benefits of the certification system and the importance of institutional quality.

Background: Extrachromosomal DNA (ecDNA), a form of circular DNA located outside chromosomes, is a common driver of oncogene amplification. Recent pan-cancer studies have associated ecDNA with cancer progression and poor prognosis. Moreover, its relationship with specific genomic features is becoming increasingly evident. However, the clinicopathological characteristics and underlying genomic mechanisms of ecDNA in gastric cancer remain poorly understood.

Methods: We analyzed whole-genome sequencing data from 81 Japanese gastric cancer samples to identify ecDNA using AmpliconArchitect and AmpliconClassifier. Gene expression profiles were obtained through whole-transcriptome RNA sequencing (RNA-seq).

Results: We found that the frequency of ecDNA occurrence was comparable across cancer stages and had a modest impact on prognosis, suggesting that ecDNA is present in early-stage disease and has a limited role in gastric cancer progression. Several immunomodulatory genes were amplified on ecDNA, and the presence of ecDNA harboring these genes was associated with the suppression of cytotoxic T cell responses, indicating a functional link between ecDNA and immune evasion. ecDNA-positive cases more frequently harbored TP53 mutations and were microsatellite stable compared to ecDNA-negative cases. Finally, ecDNA-positive tumors exhibited a high prevalence of single-base substitution signature 17, implicating that oxidative stress, potentially induced by gastric acid, plays a role in the generation of ecDNA in gastric cancer.

Conclusions: These findings provide insights into the clinicogenomic features of ecDNA in gastric cancer and highlight its potential impact on disease progression and immune modulation.

Objective: To develop and validate a nomogram for predicting lymph node metastasis in early gastric cancer according to the characteristics of the tumor microenvironment to optimize treatment strategies.

Methods: Clinicopathological data of 882 early gastric cancer patients from three medical centers were retrospectively collected. Among them, 744 cases from Center 1 were assigned to the training set, and 138 cases from Centers 2 and 3 were the validation set. Tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) were quantified in hematoxylin-eosin stained sections using QuPath software. The number and maturity of tertiary lymphoid structures (TLS) were evaluated through multiplex immunofluorescence. Nomogram prediction models were constructed using independent risk factors identified by univariate and multivariate logistic regression analyses. The performance of the model was evaluated by receiver operating characteristics (ROC) curve, calibration curve, and clinical decision curve analyses.

Results: Lymph node metastasis rates were 19.2% in the training set and 23.9% in the validation set; sex, lymphovascular invasion, TSR, and TLS were identified as independent risk factors. The model achieved an area under the ROC curve of 0.807 [95% confidence interval (CI) 0.766-0.843] in the training set and 0.822 (95% CI 0.721-0.907) in the validation set. The calibration curves indicated good agreement between predicted probabilities and actual incidence rates, and the clinical decision curve analysis revealed a positive clinical net benefit over a broad range of thresholds.

Conclusion: The nomogram developed in this study showed high accuracy, stability, and clinical utility, suggesting its value for guiding treatment decision-making in early gastric cancer.

Helicobacter pylori (H. pylori) infection is a recognized risk factor for gastric cancer (GC), which is the leading cause of cancer-related deaths worldwide. As a Class I carcinogen, H. pylori plays a central role in the occurrence and development of GC. Recent studies have highlighted the critical role of metabolic reprogramming inthe gastric cancer, and H. pylori infection has been shown to significantly alter metabolic pathways in gastric cancer. This review explores the mechanisms by which H. pylori infection drives metabolic changes in GC, particularly in glycolysis, lipid metabolism, and amino acid metabolism. By altering these metabolisms, H. pylori enhances the survival, proliferation, and metastasis of tumor cells, and also promotes immune evasion. Therefore, understanding the ways in which H. pylori-induced metabolic reprogramming of GC cells is essential for identifying new therapeutic targets. By summarizing the latest research progress of these metabolic pathways, new strategies and directions can be provided for gastric cancer treatment.

Background: Peritoneal dissemination is a major cause of poor prognosis in gastric cancer (GC). Although conventional peritoneal lavage cytology (CY) is used to detect micrometastatic peritoneal spread, its sensitivity is limited. This study aimed to evaluate the clinical utility of droplet digital methylation-specific PCR (ddMSP) targeting cancer-specific methylation for DNA-based detection of peritoneal dissemination.

Methods: Peritoneal lavage fluid was prospectively collected from 400 samples in 357 GC patients, including 360 samples from 339 patients with chemotherapy-naïve tumors. DNA was extracted, bisulfite-converted, and analyzed by ddMSP targeting CDO1 and HOPX methylation. Diagnostic performance was assessed by ROC analysis, and associations with clinicopathological features and prognosis were evaluated using logistic and Cox regression models.

Results: CDO1 and HOPX methylation levels were significantly elevated in CY1 cases compared with CY0 (p < 0.0001). CDO1 methylation demonstrated excellent diagnostic accuracy for CY1 (AUC: 0.93; sensitivity: 83.9%; specificity: 90.9%), while HOPX methylation showed slightly lower performance (AUC: 0.86). Multivariate analysis revealed that ddMSP CDO1-hi was independently associated with serosal invasion (pT4), and HOPX-hi with both pT4 and nodal metastasis. Furthermore, CDO1-hi status was an independent adverse prognostic factor for peritoneal dissemination-free survival (HR: 2.73, p = 0.018).

Conclusions: ddMSP-based detection of CDO1 methylation provides a sensitive and specific method for identifying micrometastatic peritoneal spread in GC. This DNA-based approach may serve as a valuable prognostic biomarker and contribute to improved perioperative management in gastric cancer.

Background: Prognostic factors for conversion surgery in patients with metastatic gastric cancer remain unclear. This study aimed to identify the prognostic factors associated with conversion surgery, and evaluate the safety and survival outcomes of conversion surgery using data from Japanese patients enrolled in the CONVO-GC-1 study.

Methods: Clinical background, chemotherapy before and after surgery, surgical outcomes, postoperative complications, and survival were analyzed. Prognostic factors were assessed using univariate and multivariate regression analyses.

Results: A total of 773 Japanese patients were included. Categories 1, 2, 3, and 4 included 345, 156, 225, and 47 patients, respectively. R0 resection was achieved in 571 (73.9%) patients. Incidence rate of Clavien-Dindo grade ≥ III complications was 12.0%. Surgery-related mortality rate was 0.1%. Median overall survival (OS) among patients with R0 resection was 47.8 months. The OS of patients with R0 resection by category was 47.6, 116.6, 40.1, and 54.4 months for categories 1, 2, 3, and 4, respectively. In the multivariate analysis, male sex (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.30-2.22), undifferentiated histological type (HR, 1.35; 95% CI 1.04-1.75), Eastern Cooperative Oncology Group Performance Status ≥ 1 (HR, 1.57; 95% CI 1.18-2.08), ypT4 (HR,1.79; 95% CI 1.38-2.33), ypN + (HR, 1.92; 95% CI 1.42-2.58), and preoperative chemotherapy duration < 6 months (HR, 1.43; 95% CI 1.10-1.87) were poor prognostic factors.

Conclusion: Conversion surgery was safely performed, yielding favorable survival outcomes in patients with R0 resection. Therefore, careful patient selection is warranted, particularly in those with poor prognostic indicators.

Background: In late-line treatment for advanced gastric cancer (AGC), evidence supporting the use of irinotecan in older patients remains limited. We conducted a post-hoc age-subgroup analysis of the phase III RINDBeRG study, which randomized AGC patients previously treated with ramucirumab-based chemotherapy to receive ramucirumab plus irinotecan (RAM + IRI) or irinotecan alone (IRI).

Methods: Patients were classified as elderly (≥ 70 years; n = 83 [RAM + IRI], 80 [IRI]) or non-elderly (< 70 years; n = 117, 113). Efficacy outcomes-including overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)-and safety were compared. Prognostic factors for OS were explored via multivariable Cox regression.

Results: OS and PFS did not differ significantly between age groups. In the RAM + IRI group, median OS was 9.7 vs. 8.9 months (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.63-1.15), and PFS was 4.0 vs. 3.6 months (HR 0.84, CI 0.63-1.12). In the IRI group, OS was 8.5 months in both groups (HR 0.99, CI 0.7-1.34), and PFS was 3.1 vs. 2.2 months (HR 0.87, CI 0.65-1.17). ORRs were 20.5% vs. 14.5% (RAM + IRI) and 18.8% vs. 9.7% (IRI) in elderly vs. non-elderly patients. Grade ≥ 3 adverse events were comparable. Multivariable analysis identified ECOG PS 1, peritoneal metastasis, elevated LDH, modified Glasgow Prognostic Score ≥ 1, and low alkaline phosphatase as poor prognostic factors. Age was not prognostic.

Conclusions: Irinotecan-based therapy offers comparable efficacy and tolerability in older and younger patients with refractory AGC.

Peritoneal metastasis (PM) is a major contributor to poor prognosis in advanced gastric cancer (GC), yet its molecular mechanisms remain insufficiently understood. The results of bioinformatic analysis and clinical sample validation reveal that LncRNA MZF1-AS1 is significantly upregulated in GC tissues, particularly in peritoneal metastases, and is associated with worse overall and post-progression survival. MZF1-AS1 enhances malignant phenotypes and PM of GC cells in vitro and in vivo. Mechanistically, RAB13 is demonstrated as a functional effector of MZF1-AS1 via RNA-seq. MZF1-AS1 enhances RAB13 expression by promoting its mRNA stability, thereby facilitating GC cell proliferation, EMT, migration, invasion, and stemness. Further, RNA pulldown and Mass Spectrometry reveal that MZF1-AS1 directly binds to NSUN2. MZF1-AS1 strengthens the interaction between NSUN2 and RAB13 mRNA, promoting NSUN2-mediated m5C modification and stabilizing RAB13 mRNA. Our findings uncover a novel epi-transcriptomic mechanism by which MZF1-AS1 promotes GC progression via NSUN2-dependent m5C methylation of RAB13 mRNA, offering new insights into PM pathogenesis and highlighting potential therapeutic targets for advanced GC.