Search Results (539)

Background and Objectives: The Gustave Roussy Immune (GRIm) score, reflecting systemic inflammation and nutritional status, has emerged as a simple and reproducible prognostic biomarker in various malignancies. However, its prognostic interaction with tumor microenvironmental factors remains unclear in gastric cancer. The primary aim of this study was to evaluate the prognostic value of the GRIm score in patients with resectable gastric adenocarcinoma, while the secondary aim was to determine whether integrating the GRIm score with tumor microenvironment–related pathological markers could improve prognostic stratification. Materials and Methods: This retrospective study analyzed 188 patients with resectable gastric adenocarcinoma treated at the Trakya University Faculty of Medicine between 2007 and 2018. GRIm scores were calculated from preoperative lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio (NLR) values. Pathologic parameters, including programmed death-ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1 vs. <1), tumor–stroma ratio (TSR; stromal component ≥ 50% vs. <50%), and tumor-infiltrating lymphocyte (TIL) density (CD8+ ≥ 10% vs. <10%), were evaluated on surgical specimens. Survival outcomes were assessed using Kaplan–Meier and multivariate Cox analyses. Results: The study population had a mean age of 61.8 years and was predominantly male (72.3%). Patients with low GRIm scores had significantly longer disease-free survival (DFS; 24 vs. 12 months; p = 0.004) and overall survival (OS; 32 vs. 19 months; p = 0.006). In multivariate analysis, the GRIm score remained an independent predictor for both disease-free survival (p = 0.035) and overall survival (p = 0.044). Among combined models, the GRIm–TSR classification provided the most pronounced stratification (median DFS = 35 vs. 12 months; OS = 45 vs. 19 months; p = 0.014 and 0.001, respectively), retaining independent prognostic significance (hazard ratio [HR] = 1.23; p = 0.005). Integrating GRIm with PD-L1 and TIL density also improved prognostic discrimination. Conclusions: The GRIm score is a robust and cost-effective biomarker that independently predicts disease-free survival and overall survival in resectable gastric adenocarcinoma. Its combination with microenvironmental markers—PD-L1, TIL, and TSR—captures complementary biological dimensions of tumor aggressiveness, offering an integrative and clinically feasible framework for individualized risk assessment and postoperative management. Prospective multicenter validation is warranted. Full article

Background: Intentional occlusion of the internal iliac artery (IIA) during endovascular repair of aorto-iliac aneurysms may predispose patients to pelvic ischemic complications such as gluteal claudication, erectile dysfunction, and bowel ischemia. Iliac branch devices (IBDs) have been developed to preserve hypogastric perfusion. E-Liac (Artivion/Jotec) is one of the latest modular IBDs yet reports on mid-term performance are limited to small single-center cohorts with short follow-up. The CAMpania PugliA bRanch IliaC (CAMPARI) study is a multicenter investigation of E-Liac outcomes. Methods: A retrospective observational cohort study was conducted across five Italian vascular centers. All consecutive patients undergoing E-Liac implantation for aorto-iliac or isolated iliac aneurysms between January 2015 and December 2024 were identified from prospectively maintained registries. Inclusion criteria comprised elective or urgent endovascular repair of aorto-iliac aneurysms in which an adequate distal sealing zone was not available without covering the IIA and suitability for the E-Liac device according to its instructions for use (IFU). Patients with a life expectancy < 1 year or hostile anatomy incompatible with the IFU were excluded. The primary end point was freedom from branch instability (occlusion/stenosis, kinking, or detachment of the bridging stent). Secondary end points included freedom from any endoleak, freedom from device-related reintervention, freedom from gluteal claudication, aneurysm-related and all-cause mortality, acute renal failure, and sac regression > 5 mm. Results: A total of 69 consecutive patients (68 male, 1 female, median age 72.0 years) received 74 E-Liac devices, including 5 bilateral implantations. The mean infrarenal aortic diameter was 45 mm and the mean CIA diameter 34 mm; 14 patients (20.0%) had a concomitant IIA aneurysm (>20 mm). Concomitant fenestrated or branched aortic repair was performed in 23% of procedures. Two patients received a standalone IBD without implantation of a proximal aortic endograft. Technical success was achieved in 71/74 cases (96.0%); three failures occurred due to inability to catheterize the IIA. Distal landing was in the main IIA trunk in 58 cases and in the posterior branch in 13 cases. Over a median follow-up of 18 (6; 36) months, there were four branch instability events (5.4%): three occlusions and one bridging stent detachment. Seven patients (9.5%) developed endoleaks (one type Ib, two type II, two type IIIa, and two type IIIc). Five patients (6.8%) required reintervention, and five (6.8%) reported gluteal claudication. There were seven all-cause deaths (10%), none within 30 days or related to aneurysm rupture; causes included COVID-19 pneumonia, acute coronary syndrome, melanoma, gastric cancer, and stroke. No acute renal or respiratory failure occurred. Kaplan–Meier analysis showed 92% (95% CI 77–100) freedom from branch instability in the main-trunk group and 89% (60–100) in the posterior-branch group (log-rank p = 0.69). Freedom from any endoleak at 48 months was 87% (95% CI 75–95), and freedom from reintervention was 93% (95% CI 83–98). Conclusions: In this multicenter cohort, the E-Liac branched endograft demonstrated high technical success and favorable early–mid-term outcomes. Preservation of hypogastric perfusion using E-Liac was associated with low rates of branch instability, endoleak, and reintervention, with no 30-day mortality or aneurysm-related deaths. These findings support the safety and efficacy of E-Liac for aorto-iliac aneurysm management, although larger prospective studies with longer follow-up are needed. Full article

A key function of naturally occurring antibodies is to control pathologically altered cells, such as those with aberrant glycosylation. Age-related diminution in the pool of B cells producing these immunoglobulins is linked to impaired anti-tumor immunity. In this study, the levels of antibodies against tumor-associated carbohydrate antigens (TACAs)—common in gastric cancer (GC) and other malignancies—were analyzed in 235 treatment-naïve GC patients (stages I–IV) and 76 healthy donors using a printed glycan array (PGA). We found that anti-glycan IgM levels, but not IgG, reduced with age in both patients and donors. Crucially, IgM levels against most glycans were significantly lower in the GC cohort compared with healthy donors, a trend that remained after age adjustment. Furthermore, an immunohistochemical analysis revealed that human anti-GalNAcα (Tn) antibodies—a well-characterized TACA in gastrointestinal cancers—bound to tumor cells and exhibited perinuclear and membrane staining in non-tumor surface cells within the same organ. These data support the hypothesis that gastric cancer patients have reduced levels of anti-glycan IgMs, which are responsible for the early recognition of transformed cells. This specific immunodeficiency may contribute to a permissive environment for tumor development. Full article

Background/objectives: Metabolic abnormalities, independent of excess weight, may contribute to cancer risk even among individuals of normal weight, though their role remains unclear. This study sought to ascertain if metabolically unhealthy normal-weight (MUNW) individuals, generally characterized by a normal body mass index alongside the presence of metabolic abnormalities, have higher cancer risk than metabolically healthy peers, to analyze variations in risk across obesity-related cancer types, and to examine which single specific metabolic components can predict cancer independently in normal-weight individuals. Methods: Two authors systematically searched the PubMed, EMBASE, and Web of Science databases for longitudinal studies, published from inception to July 2025, that included normal-weight adults, classified participants by metabolic health status, and reported incident cancer outcomes in metabolically unhealthy versus healthy normal-weight groups. Hazard ratio (HR) estimates were extracted from each study and were pooled using random-effects inverse-variance model with empirical Bayes variance estimator. Results: Thirty-five studies involving 18,210,858 participants (56.0% females, mean age = 53.8 years) were included. A total of 280,828 new cancer cases were diagnosed during follow-up (mean = 10.6 years). In comparison with metabolically healthy normal-weight individuals, MUNW individuals had a 20% higher risk of cancer (HR = 1.20, 95% confidence interval [CI]: 1.13–1.28). Increased risks were observed for gastric cancer (HR = 1.40, 95% CI: 1.04–1.87), pancreatic cancer (HR = 1.37, 95% CI: 1.21–1.54), and colorectal cancer (HR = 1.34, 95% CI: 1.14–1.57), which were the cancer types showing statistically significant associations in subgroup analyses. Normal-weight participants presenting specific metabolic factors like central adiposity or glucose metabolism abnormalities had a 20% (HR = 1.20, 95% CI: 1.13–1.37) and 23% (HR = 1.23, 95% CI: 1.06–1.41) increased cancer risk, respectively. Conclusions: MUNW individuals are at higher risk of cancer, with specific metabolic abnormalities, particularly central adiposity and impaired glucose regulation, emerging as the factors most strongly associated with increased risk in normal-weight individuals. Routine metabolic screening and detailed phenotyping are crucial to identify these risks. Full article

Background. The aim of this study was to develop a predictive model of anticancer drug therapy toxicity in patients with gastric cancer. Methods. The retrospective study included 100 patients with stage II–IV gastric cancer who underwent 4 chemotherapy cycles. Initial significant toxicity factors included age, gender, height, body mass, body mass index, disease stage, skeletal muscle index (SMI), as well as plasma levels of trace elements (copper, zinc, selenium, manganese) and thyroid-stimulating hormone, cancer histology type and treatment regimen. The CTCAE v5.0 scale was employed to assess the severity of adverse events. Statistical analysis and building of mathematical neural network models were carried out in SPSS Statistics (v19.0). Results. Lower SMI values were associated with higher rates of toxicity-related complications of anticancer drug therapy (p < 0.05): leukopenia, hypoproteinemia, nausea, vomiting, cardiovascular events. Anemia, thrombocytopenia, hepatic cytolysis syndrome, nausea, diarrhea, constipation and stomatitis showed a weaker correlation with SMI. An increase in TSH was associated with higher rates of thrombocytopenia, nausea and vomiting. A decrease in Cu/Zn in plasma correlated with the severity of leukopenia and diarrhea, whereas Se/Mn showed an inverse correlation with the severity of anemia. Conclusions. Sarcopenia, abnormal thyroid status and imbalances in copper, zinc, selenium and manganese in blood plasma of patients with gastric cancer may be used as predictors of increased toxicity of anticancer drug therapy. Full article

Gastric cancer remains a leading cause of cancer-related mortality worldwide. Citrus fruits are rich in polyphenols, exerting antioxidant and chemo-preventive activities, and lemon peel represents a valuable source of such bioactive compounds. Previous studies showed that Citrus limon peel extracts (LPE) inhibited the activity of some enzymes of the antioxidant system and reduced the interleukin-6-dependent invasiveness of gastric and colon cancer cells. In the present study, we have investigated the effects of LPE on the human gastric adenocarcinoma AGS and MKN-28 cells and on the activity of a crucial redox enzyme, catalase (CAT). Indeed, LPE significantly reduced the cell viability and clonogenic potential of the gastric cancer cells and induced morphological changes indicative of cytotoxicity. Moreover, LPE modulated the intracellular redox homeostasis by decreasing levels of the hydrogen peroxide-related reactive oxygen species (ROS) while increasing those of superoxide anions and decreasing levels of superoxide dismutases (SODs). Western blotting analysis revealed that LPE downregulated CAT, SOD-1, SOD-2, and monoamine oxidase A (MAO-A) protein expression level in both cell lines. Finally, the extract inhibited CAT activity in a dose-dependent manner (IC₅₀ = 0.008 ± 0.003 mg/mL; K_i = 0.012 ± 0.002 mg/mL). These findings indicate that LPE exerts cytotoxic and redox-modulating effects through the inhibition of antioxidant enzymes and the alteration of ROS balance. Therefore, the agro-industrial by-product LPE could be considered as a promising natural source of polyphenolic compounds with potential applications in the prevention and therapy of gastric cancer. Full article

Background and Objectives: The tumor-node-metastasis (TNM) classification system is the standard for staging gastric cancer and predicting survival. However, its accuracy can be compromised by insufficient lymph node (LN) dissection during surgery or inadequate pathologic examination. Alternative staging systems, such as the lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS), may provide better prognostic value when LN examination is suboptimal. Because the current N staging system was not able to accurately stratify patients relative to their survival outcomes in our series, this study assessed the prognostic impact of LNR and LODDS on overall survival (OS) of patients who underwent radical gastrectomy for cancer. Materials and Methods: Between March 2005 and June 2025, the authors performed gastrectomy for gastric carcinoma in 114 patients. Out of these patients, 39 were excluded (19 had stage IV, while 20 underwent palliative gastrectomy with D1 lymphadenectomy). Thus, the study cohort included 75 patients who underwent curative gastrectomy, with 4 (5.3%) of them dying postoperatively. Potential prognostic factors associated with OS (including age, sex, tumor location, T stage, N stage, TNM stage, LNR, and LODDS) were evaluated by univariate and multivariate analysis. Because the recurrence data were missing in 41 patients, the disease-free survival (DFS) analysis would not be meaningful. Results: The OS analysis was based on the 71 patients surviving postoperatively. Because successive N stage groups could not accurately stratify patients according to their OS, we used X-tile software version 3.6.1 to identify two cut-offs (both for LNR and LODDS) that were able to stratify patients in three subgroups with significantly distinct survival outcomes. Multivariate analysis found that both LODDS and LNR systems were independent prognostic factors for OS. Conclusions: LNR and LODDS provide more detailed insights into lymph node status and have demonstrated potential for enhancing prognostic accuracy compared to N staging, even in patients who underwent curative gastrectomy with D2 lymphadenectomy. Although LNR and LODDS are usually useful in patients who underwent suboptimal lymphadenectomy, the current study demonstrated that these systems could improve prognostic stratification even in patients with more than 15 retrieved LNs. However, due to the small sample size, the current observations and proposed cut-offs of LNR and LODDS have to be validated in larger studies including such patients. Full article

Background and Aims: Gastric cancer remains a major health burden in East Asia. Gastrectomy is a primary treatment, yet postoperative malnutrition—particularly inadequate protein intake—adversely affects outcomes. This study assessed the association between achieving ≥70% of the recommended protein intake one year after gastrectomy and three-year survival. Methods: In this prospective, single-center, observational study, 69 patients with newly diagnosed gastric cancer who underwent gastrectomy between January 2021 and August 2023 were enrolled. Four patients who died within one year postoperatively were excluded, leaving 65 patients for analysis. Protein intake achievement rate (PIAR) at 12 months was calculated based on a recommended intake of 1.2 g/kg/day, and patients were stratified as PIAR ≥ 70% or <70%. Overall survival was analyzed using time-to-event methods, with a median follow-up of 2.1 years. Results: Among the 65 patients (median age 62 years, IQR 56–68; 56.9% male), 75.4% underwent subtotal gastrectomy. At 12 months, 7 patients (10.8%) failed to achieve a PIAR ≥ 70%. Compared with patients achieving adequate protein intake, those with inadequate intake more frequently underwent total gastrectomy (71.4% vs. 19.0%, p = 0.008) and had advanced-stage disease (Stage III–IV: 85.7% vs. 39.7%, p = 0.039). Kaplan–Meier analysis demonstrated significantly lower survival in the inadequate protein group, with a hazard ratio of 13.02 (95% CI 2.53–66.93); the wide confidence interval reflects the small number of patients with inadequate intake (n = 7). Conclusions: Failure to achieve ≥70% of recommended protein intake one year after gastrectomy is a strong independent predictor of mortality, associated with a 13-fold higher risk of death. Nutritional monitoring and early intervention are crucial, particularly for patients with total gastrectomy or advanced disease. Full article

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are microbial metabolites with recognised roles in gut and immune homeostasis, but their therapeutic relevance in gastric cancer, particularly in combination with chemotherapeutics, remains unclear. This study investigated the antiproliferative synergy between a combined SCFA mixture (APB) and doxorubicin (Dox) in AGS gastric adenocarcinoma cells using integrated cellular, molecular, and proteomic approaches. APB and Dox each inhibited cell proliferation, with IC₅₀ values of 568.33 ± 82.56 μg/mL and 0.22 ± 0.04 μg/mL, respectively, and their combination (3000 + 0.27 μg/mL) enhanced cytotoxicity, achieving 103.46% inhibition and reducing the APB IC₅₀ to 512.80 ± 18.37 μg/mL. Combination index values confirmed synergistic interactions (CI₅₀ = 0.61; CI₉₅ = 0.13). APB+Dox significantly increased apoptosis (94.83%) with minimal necrosis (4.64%) and induced strong ROS generation comparable to APB alone, while Dox showed limited oxidative effects. Proteomic profiling revealed downregulation of ribosomal proteins and cell cycle regulators in Dox and APB+Dox groups, with the combination further enhancing apoptosis-related pathways and stress responses. Overall, these findings indicate that SCFA-based interventions, exemplified by APB+Dox, may offer a low-toxicity strategy to potentiate chemotherapy efficacy in gastric cancer through apoptosis induction, redox disruption, and attenuation of drug resistance. Full article

Background/Objectives: Incidence of malnutrition varies greatly among gastrointestinal (GI) cancer patients and has a major impact on prognosis. We performed a meta-analysis to identify risk factors for malnutrition risk, malnutrition diagnosis, and cachexia in patients with GI cancer. Methods: A systematic search was performed on 31 October 2025 on the PubMed (Medline), Embase, and Cochrane Library databases. Eligible studies reported on risk factors for malnutrition risk, malnutrition diagnosis, malnutrition-related complication risk and cachexia in adult patients with GI cancer. Articles on neuroendocrine tumours, primary cancer outside the GI tract, and the paediatric population were excluded. The random-effects model yielded the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the investigated risk factors. Results: A total of 37,624 records were identified. Data from 262,525 patients from 578 articles were included in the analysis. Older age (≥65) was associated with higher odds for malnutrition risk across all GI cancers. In gastric cancer, males had a lower odds for malnutrition risk (OR 0.84; 95% CI 0.75–0.95); however, the sex difference across other cancer types was heterogeneous, and mostly not significant. Tumour location influenced the odds for malnutrition-related complication risk in pancreatic ductal adenocarcinoma (head vs. body/tail—OR 1.48; 95% CI 0.98–2.23) and colorectal cancer (colon vs. rectal—OR 1.39; 95% CI 1.07–1.81; right-sided vs. left-sided—OR 1.54; 95% CI 1.34–1.77). Increased C-reactive protein alone indicated higher odds for malnutrition risk at baseline. Conclusions: Inflammatory biomarkers and tumour characteristics may indicate malnutrition risk in GI cancer at baseline. There is a great need for standardised and harmonised approaches in nutritional status assessment in GI cancer. Full article

Objectives: In the absence of massive screening programs, it is imperative to develop and validate a candidate selection strategy for opportunistic endoscopic screening (OES) targeting the early detection of gastric cancer. Methods: A hospital-based cross-sectional study was conducted, enrolling both health check-up controls and gastric cancer patients. Data collection included two components: (1) a questionnaire including demography, self-reported comorbidities, and family history of cancers; (2) serology including hemoglobin, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Associations between potential variables and gastric cancer risk were assessed and the predictive efficacy of these risk factors was quantified. Sequentially, risk stratification scoring systems were constructed and their cost-effectiveness profiles were evaluated. Results: A total of 58,218 participants were included in the analysis, among whom 619 (1.1%) were gastric cancer patients. Multivariate analyses identified male, age >40 years, family history of gastric cancer, comorbidities of upper digestive tract benign diseases (UDTBDs), anemia, and elevated serum CEA and/or CA19-9 as independent risk factors of increasing gastric cancer risk. Cost-effectiveness analysis demonstrated that individuals, especially those symptomatic, presenting any of following conditions should be recommended for OES: (1) age ≥50 years, (2) family history of gastric cancer, and/or (3) comorbid UDTBDs. Elsewise, unclear anemia and/or elevated serum CEA and/or CA19-9 presenting among males and/or persons 41–50 years of age should be considered for OES. Notably, this selection strategy achieved a detection rate comparable to that of alternative protocols while yielding superior cost-effectiveness outcomes. Conclusions: The integrated strategy combining questionnaire and sequential serology represents an effective and cost-effective approach to identifying high-risk candidates for gastric cancer OES. Further investigations are warranted to develop more precise and tailored screening and surveillance protocols, with the aim of optimizing both detection rates and cost-effectiveness in clinical practice. Full article

Background/Objectives: The COVID-19 pandemic disrupted healthcare delivery worldwide, potentially delaying the diagnosis and treatment of oncologic diseases. This study aimed to evaluate the impact of the pandemic on stage at diagnosis, treatment allocation, and survival outcomes among patients with gastric cancer. Methods: We retrospectively analyzed 419 consecutive patients diagnosed with gastric cancer between January 2018 and December 2021 at a tertiary oncology–surgical center. Patients were divided into pre-pandemic (2018–2019) and pandemic (2020–2021) cohorts. Demographic, clinical, and treatment variables were compared using t-tests and χ² tests. Multivariate logistics and Cox regression models were applied to identify independent predictors of metastatic presentation and mortality. Overall survival (OS) was calculated from diagnosis to death or last contact (OS_days), with same-day events censored at time zero. Results: Baseline characteristics were comparable between cohorts (age, p = 0.098; sex, p = 0.137; residence, p = 0.345). The proportion of metastatic cases (M1) increased from 42.8% in 2018–2019 to 64.4% in 2020–2021 (χ² p < 0.001). Surgical rates remained stable (55.1% vs. 47.7%, p = 0.161). Diagnosis during the pandemic independently predicted metastatic presentation (OR = 2.63, 95% CI 1.68–4.11, p < 0.001) and higher mortality (HR = 1.72, 95% CI 1.41–2.03, p < 0.001). Kaplan–Meier analysis confirmed significantly reduced OS in the pandemic cohort (log-rank χ² = 81.29, p < 0.001). Conclusions: The pandemic was associated with delayed diagnosis, stage migration toward advanced disease, and inferior survival in gastric cancer, despite comparable demographics and treatment capacity. These findings emphasize the need to safeguard diagnostic pathways—particularly endoscopy—during healthcare crises to prevent avoidable oncologic deterioration. Full article

Introduction: Although patients with upper gastrointestinal (GI) cancer have an increased risk of developing small intestinal bacterial overgrowth (SIBO) due to disease- and treatment-related factors, SIBO remains underdiagnosed in oncology. Aim and Methods: This prospective study evaluated the prevalence of SIBO and its impact on symptom-related quality of life (QoL) in patients with current or prior upper GI cancer. Between April 2021 and May 2022, patients reporting SIBO-related symptoms like bloating and/or diarrhea completed a standardized symptom questionnaire. QoL impact was scored from 0 (none) to 3 (severe). Patients with scores > 1 and no recent antibiotic use underwent upper endoscopy with duodenal aspirate. SIBO was defined as >10³ CFU/mL. Results: Ninety patients were enrolled (51% female; median age of 65 years): 35% had pancreatic, 34% gastric, 17% biliary, and 14% esophageal cancer. Sixty reported SIBO-related symptoms: 35% reported bloating, 11% diarrhea, and 54% both. Of these, 36 underwent endoscopy; 53% were diagnosed with SIBO. Among SIBO-positive patients, 95% reported bloating and 58% reported diarrhea. Prior abdominal surgery was recorded in 63% of SIBO cases. Conclusions: SIBO was identified in more than half of symptomatic upper GI cancer patients, with a strong association with bloating and previous abdominal surgery. These findings emphasize the importance of clinical awareness and appropriate diagnostic evaluation for SIBO in this high-risk group to improve symptom control and quality of life. Full article

Epstein–Barr virus (EBV) infection is closely associated with gastric cancer, yet its role in m6A-dependent gene regulation remains poorly understood. In this study, we investigated how EBV infection alters the m6A methylation pattern in gastric cancer cells and examined its impact on TSC22D1 mRNA stability through interaction with the m6A reader protein YTHDF1. m6A RNA immunoprecipitation sequencing (MeRIP-seq) revealed a significant reduction in m6A methylation of TSC22D1 in EBV-infected gastric cancer cells (AGS-EBV) compared with EBV-negative cells (AGS). Moreover, YTHDF1 knockdown increased both the stability and expression of TSC22D1. These findings demonstrate that YTHDF1 binds to TSC22D1 mRNA and promotes its m6A-dependent degradation. Collectively, our results suggest that EBV infection modulates m6A modification to regulate gene stability and identify the YTHDF1–TSC22D1 axis as a potential therapeutic target in EBV-associated gastric cancer. Full article

Gastric cancer (GC) continues to be a major cause of cancer-related deaths globally, primarily due to resistance to standard treatments like 5-fluorouracil (5FU). The transforming growth factor-β (TGF-β) signaling pathway is recognized as a key contributor to tumor progression and resistance to therapy. This work investigated the therapeutic potential of targeting TGF-β receptor I (TGFBR1) with the selective inhibitor SB431542 to enhance the effect of 5FU in GC. Analysis of public gene expression datasets revealed that increased levels of TGF-β and TGFBR1 are significantly connected with poor prognosis, particularly in high-grade GC. In vitro experiments using AGS and SNU-1 cell lines demonstrated that co-treatment with SB431542 and 5FU significantly reduced cell viability, making GC cells more sensitive to 5FU. This combination treatment led to a significant activation of caspase-dependent apoptosis, indicating an enhanced pro-apoptotic effect. These findings suggest that TGFBR1 inhibition could provide a strategic approach to reduce the dosage of 5FU, thereby minimizing its severe side effects in gastric cancer patients. Furthermore, these results underscore the potential of TGFBR1 as both a prognostic biomarker and a therapeutic target, warranting further investigation in aggressive forms of gastric cancer. Full article