Gastric cancer, one of the deadliest gastrointestinal tumors, has a high incidence rate worldwide. Many studies show that the glycosyltransferase 8 domain-containing protein 1 (GLT8D1) plays a crucial role in protein glycosylation. However, few scholars have explored the prognostic importance of GLT8D1 in gastric cancer. The purpose of this research is to investigate the clinical value and biological function of GLT8D1 by examining multiple databases and performing relevant experiments. This study obtained the transcriptomic information and clinically relevant data from the cancer genome atlas (TCGA) and evaluated GLT8D1 in pan-cancer and gastric cancer. The prognostic role of GLT8D1 in the TCGA-stomach adenocarcinoma (STAD) dataset and gastric cancer patients was explored. A predictive nomogram was developed based on GLT8D1 mRNA expression level and clinical features. The receiver operating characteristic curve (ROC) values of predicting overall survival probabilities in the training set (TCGA-STAD dataset) and external validation sets (GSE62254 and FAHSYSU's cohort) were investigated to evaluate the performance of the prognostic nomogram. The STRING database and GeneMANIA were used to describe the proteins and genes interacting with GLT8D1. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and gene set enrichment analysis (GSEA) were used to analyze the biological function of GLT8D1 based on the TCGA-STAD dataset. The study also performed in vitro assays to evaluate the proliferation, invasion, and migration abilities of GLT8D1 in gastric cancer cells. The results found that GLT8D1 is upregulated in gastric cancer. In addition, according to the study, those with stomach cancer who had increased GLT8D1 expression had decreased overall survival (OS). Moreover, GLT8D1 was identified as a separate risk factor for OS in gastric cancer by the univariate and multivariate analyses. Nomogram evaluation revealed that the predictive model was reliable for estimating the probability of overall survival over 1, 3, and 5 years. Functional enrichment analysis showed that interferon-gamma response, mTORC1 signaling pathway, glycolysis, and IL6-JAK-STAT3 signaling pathways were enriched in patients with high GLT8D1 expression levels. Our in vitro assay experiment revealed that GLT8D1 promotes gastric cancer cell invasion and migration, which suggests the involvement of activating the IL6/STAT3 signaling pathway. The study concludes that GLT8D1 is a prognostic biomarker that suggests an unfavorable prognosis for gastric cancer.
Icaritin, a natural anti-cancer agent, is known to target STAT3 and inhibit glycolysis in hepatocellular carcinoma (HCC), but the connecting mechanism has been elusive. In this study, we identified the glycolytic enzyme aldolase B (ALDOB) as a key target of icaritin by transcriptome sequencing of icaritin-treated hypoxic HepG2 cells. Icaritin significantly inhibited HCC cell proliferation and glycolysis, and these effects were substantially reversed by overexpression of ALDOB. At the molecular level, icaritin suppressed STAT3 promoter activity and mRNA expression. Crucially, a chromatin immunoprecipitation (ChIP) assay revealed that icaritin reduced the enrichment of histone H3K18 lactylation (H3K18la) and its associated enrichment of p300 on the STAT3 promoter. This suppressive effect was rescued by the addition of exogenous lactate, directly linking lactate's availability to the epigenetic activation of STAT3. These findings revealed that icaritin suppresses STAT3 transcription in HCC through inhibiting ALDOB-mediated glycolysis, ultimately reducing the glycolysisdependent H3K18la modification on the STAT3 promoter. This work identifies a critical metabolism-epigenetics pathway, providing a foundational mechanism for icaritin's anti-tumor effect.
SMARCA4-deficient tumors represent a group of highly aggressive malignancies defined by the loss of SMARCA4 (BRG1) protein expression and have been most frequently described in thoracic and gynecologic organs. Reports of SMARCA4 deficiency in primary hepatocellular carcinoma (HCC) remain exceedingly rare. We describe a case of SMARCA4-deficient hepatocellular carcinoma with extensive metastatic involvement. A 75-year-old man with a prior diagnosis of HCC developed pulmonary nodules following transarterial chemoembolization (TACE). Histopathological evaluation of a lung biopsy demonstrated metastatic hepatocellular carcinoma with complete loss of SMARCA4 expression on immunohistochemistry. The tumor exhibited poorly differentiated morphology and aggressive clinical behavior, with rapid progression despite systemic therapy. This case highlights the clinicopathological features of SMARCA4-deficient hepatocellular carcinoma, underscores the importance of incorporating molecular pathological evaluation into routine liver cancer diagnostics, and provides insight into the implications of SMARCA4 deficiency for therapeutic decision-making.
Chimeric Antigen Receptor T (CAR-T) Cell Therapy has been successful in curing hematologic malignancy but has not shown any results on solid tumors. One big obstacle is lack of dispersal coupled with CAR-T cells remaining undetected in the sick tissue environment. IL-9 (interleukin-9) retains T cells survival and function to improve antitumor immune reactions. This study developed Claudin18.2-targeted CAR-T cells that constantly expressed IL-9. It studied their ability to fight tumors in mice with working immune systems suffering from tumors. In vitro, it was found that the proliferative and chemotactic abilities of IL-9 expressing CAR-T cells are strong, but their cytotoxicity against Claudin18.2+ tumor cells is the same as that of regular CAR-T cells. In vivo, in treatment with IL-9, CAR-T cells showed a much stronger effect on tumor growth with the pancreatic model, melanoma model, and hepatocellular carcinoma model than in vitro, with the therapeutic effects improving, with the number of CAR-T cells getting bigger. With better results, more CAR-T cells are formed with a higher infiltration into the tumor, therefore more IFN-gamma, IL-2, and granzyme B. IL-9 expression gives rise to internal T cell development, which become a central storage, which could potentially retain anti-tumor immunity. IL-9 also has some pretty good results with improving efficiency and half-life of Claudin18.2-specific CAR-T cells, it might also be a good way to make solid cancer CAR-T therapies more effective.
Adjuvant chemotherapy (ACT) is the standard treatment for Stage II-III gastric cancer after surgery, but biomarkers to guide patient selection are lacking. This study investigated whether spatial quantification of specific immune cell subsets could serve as such a biomarker. We performed multiplex immunofluorescence on postoperative specimens from 47 patients with Stage II-III gastric cancer. Immune cells were quantified in the tumor parenchyma and stroma. Their associations with overall survival (OS) and disease-free survival (DFS) were analyzed. High M1 macrophage density (in both the parenchyma and stroma), high parenchymal CD56dim natural killer (NK)-cell density, and high stromal M2 macrophage density were significantly associated with better OS and DFS in patients receiving ACT. Importantly, only patients with high M2 macrophage density derived a significant OS benefit from ACT compared with observation alone, in either the parenchyma or stroma (e.g., parenchyma: hazard ratio [HR] = 0.28, 95% confidence interval [CI]: 0.08-0.96, p = 0.029; stroma: HR = 0.14, 95% CI: 0.03-0.66, p = 0.003). A significant DFS benefit from ACT was also observed in patients with high stromal M2 density (HR = 0.22, 95% CI: 0.06-0.86, p = 0.016). No other immune cell subset consistently predicted the benefit of ACT. In conclusion, the pre-existing density and spatial distribution of tumor-associated macrophages are key determinants of prognosis and ACT's efficacy in gastric cancer.
This study aimed to investigate the effects of 3-week postdischarge oral nutrition supplements (ONS) on nutritional status, body weight (BW), body composition, immune status, and inflammatory responses in malnourished gastrointestinal cancer (GIC) patients after surgery. A retrospective observational study was carried out in a real-life clinical setting from December 2021 to December 2022. Malnourished GIC patients were recommended to receive ONS for up to 3 weeks. Nutritional status was evaluated by a patient-generated subjective global assessment. The changes in the clinical outcomes of BW, body composition, and the status of immunity and inflammation were compared between Week 3 and the baseline, stratified by appendicular skeletal muscle mass index (ASMI) and chemotherapy. Among 35 GIC patients, ONS improved the nutritional status of severe malnutrition from 57.1% at baseline to 17.1% at Week 3. Slight increases in BW and skeletal muscle mass were observed among patients with a normal ASMI. Slight increases in fat mass and visceral fat area were found among patients receiving chemotherapy. This ONS program maintained stable immunity and a controlled inflammatory status (C-reactive protein, prognostic nutritional index, and systemic immune-inflammation) among patients, with greater stability observed among those with a normal ASMI. However, these changes did not reach statistical significance. In summary, postdischarge ONS improved nutritional status in malnourished GIC patients after surgery. These findings suggested that short-term postdischarge ONS may contribute to initial progress via improved muscle mass, stabilized immunity, and controlled inflammation, particularly in patients not receiving chemotherapy.
Acute multiple cerebral infarctions as the initial manifestation of multiple primary malignant neoplasms are very rare. Studies have shown that it may even be the initial manifestation of occult systemic malignancy in up to 3% of patients. We retrospectively reported a 74-year-old male who initially presented with right hemiparesis. Magnetic resonance imaging and diffusion-weighted imaging of the brain showed acute small infarcts in the left parietal and right temporal lobes, and acute multiple cerebral infarctions were diagnosed. At the same time, computed tomography scans of the chest and abdomen revealed the concurrent ileocecal wall thickening and a left pleural mass with associated adjacent rib destruction. Subsequently, colonoscopy and biopsy of the rib lesion confirmed that the patient was diagnosed with synchronous ileocecal adenocarcinoma and plasmacytoma. Given that cerebral infarction may be the first sign of multiple primary malignant neoplasms, a precise etiological diagnosis is crucial to guiding treatment strategies and optimizing clinical prognosis.
Biliary tract cancers (BTCs) exhibit substantial genomic heterogeneity, which is further compounded by the presence of co-mutations, thereby increasing therapeutic complexity. Utilizing a large discovery cohort of 2,378 patients and an independent immunochemotherapy (ICT) cohort of 59 patients, this study investigates the patterns of co-mutation in BTCs and their clinical implications. We identified co-mutation features with potential relevance for guiding targeted therapeutic strategies. Furthermore, we delineated deleterious co-mutations (DCMs) and deleterious single mutations (DSMs) associated with adverse clinical outcomes. By integrating DCMs and DSMs, we classified BTCs into three genomic subtypes: wild-type (WT), single-hit (SH), and multi-hit (MH). The MH subtype is characterized by a high co-mutation burden and specific mutational signatures. Despite having a high prevalence of microsatellite instability and abundant actionable alterations, this subtype shows a significantly worse response to ICT. It is also associated with shorter overall survival. In contrast, the WT subtype exhibits the best outcomes. Our findings provide a molecular framework for stratifying BTC patients. MH tumors might be prioritized for genotype-matched targeted therapy, although direct comparative evidence is still lacking.
This review elucidates the intricate interplay between regulated cell death pathways-autophagy, ferroptosis, and cuproptosis-and their synergistic potential for immunotherapy in gastrointestinal tumors. By systematically dissecting the molecular mechanisms of these pathways, the authors highlight their dynamic regulation of the tumor immune microenvironment, including antigen presentation, metabolic competition, and immune evasion. Key insights include autophagy-mediated programmed death ligand-1 degradation, ferroptosis-driven immunogenic feedback via lipid peroxidation, and cuproptosis-induced mitochondrial collapse through copper-dependent proteotoxic stress. The review critically evaluates emerging combination strategies, such as autophagy inhibitors with immune checkpoint inhibitors, iron/copper-targeted nanomedicines coupled with photothermal therapy, and metabolic reprogramming interventions. These approaches demonstrate enhanced efficacy in overcoming drug resistance and reversing the immunosuppressive features of the tumor immune microenvironment. Despite promising preclinical advances, challenges such as tumor heterogeneity, spatiotemporal regulation of cell death-immune crosstalk, and clinical translation barriers are underscored. The authors advocate for multidisciplinary integration of nanotechnology, artificial intelligence, and multi-omics to optimize precision therapies. This work provides a robust framework for leveraging regulated cell death pathways to refine immunotherapy paradigms in gastrointestinal tumors, from mechanistic discoveries to actionable clinical strategies.
Secondary cervical malignancies commonly arise from adjacent reproductive tract tumors, whereas metastatic spread from gastric carcinoma to the cervix is exceedingly rare. A rare case of cervical metastasis in a 70-year-old Chinese female with a history of gastric cancer treated by curative gastrectomy six years prior is presented; she presented with anal tenesmus, and dull left lower abdominal pain. Pelvic MRI revealed space-occupying lesions involving the cervix, with pathological evaluation suggesting a gastrointestinal origin, and a multidisciplinary team (including oncologists, pathologists, and radiologists) confirmed the rectal lesion resulted from extrinsic compression due to peritoneal dissemination of gastric cancer rather than a primary rectal tumor. The patient subsequently underwent chemotherapy (oxaliplatin + capecitabine) plus immunotherapy (sintilimab), achieving a notable treatment response: normalization of tumor markers (CA72-4), significant regression of cervical and rectal lesions, resolution of intestinal obstruction symptoms, and partial remission (PR) per RECIST 1.1 criteria. Treatment for cervical cancer differs significantly from that of gastric cancer; thus, in patients with a history of gastric cancer presenting with a cervical mass, the possibility of gastric cancer recurrence should be carefully considered, and a tissue biopsy is essential to confirm the diagnosis and guide appropriate treatment strategies.
To investigate the symptom burden and self-management strategies in esophageal cancer patients undergoing chemoradiotherapy,and to establish a foundation for developing symptom management interventions, this research adopted a qualitative method using purposive sampling. The sample was selected from 19 esophageal cancer patients who were inpatients at a tertiary hospital in Nanjing, China, from December 2022 to June 2023. All of them were undergoing radiotherapy and chemotherapy. The research method was semi-structured in-depth interviews. The content of the interviews was summarized and analyzed with Colaizzi's seven-step method. The content was divided into three categories and several topics. Category 1 (core symptoms) mainly included dysphagia, treatment-related toxicities (chemotherapy-induced adverse reactions), and reflux-associated symptoms (including chronic cough). Category 2 (barriers to managing symptoms) included maladaptive coping behaviors, escalation of psychological distress, lacking information, and change in the social roles. Category 3 (management approaches) included adopting a more healthy dietary and habits, gaining more support from social networks, and maintaining a positive attitude. The patients of esophageal cancer suffer from the major symptoms of chemoradiotherapy. To face the impact of multiple symptoms, some patients used positive strategies to deal with the problem successfully and gained social support; their symptoms were relieved effectively and the patients' quality of life improved. These findings provide a strong proof for discussing individualized self-care practices.
Exosomal microRNAs (miRNAs) have emerged as promising biomarkers for gastric cancer (GC) prognosis. In this study, 76 GC patients treated at Changzhou Second People's Hospital (October 2020-May 2022) were prospectively enrolled, with monthly telephone follow-up to collect mortality and survival data for calculating overall survival. Exosomal miRNAs and clinical and pathological data from these patients constituted the training cohort, while validation was performed using a 400-patient cohort from The Cancer Genome Atlas database. A novel five-exosomal miRNA signature (miR-652-3p, miR-184, miR-340-3p, miR-96-5p, and miR-29a-3p) was identified as associated with overall survival. The resulting nomogram, which integrates this miRNA signature with key clinicopathological factors, achieved prognostic discrimination (C-index: 0.82). These findings demonstrate the clinical utility of this tool for individualized risk stratification.
This study evaluated the efficacy and safety of endoscopic papillectomy for duodenal papillary adenoma through a retrospective analysis of 18 patients (11 males, 7 females) treated at the Endoscopy Center of Jiangsu Provincial Hospital of Chinese Medicine between January 2022 and December 2024. All patients underwent complete lesion resection in a single session, with 11 cases managed by endoscopic mucosal resection (EMR) and 7 by endoscopic submucosal dissection (ESD), achieving an R0 resection rate of 94.44% (17/18). Postoperative stenting included pancreatic duct placement in 11 patients, biliary duct placement in 2 patients, and dual pancreaticobiliary stenting in 5 patients. Delayed bleeding occurred in 9 patients, all successfully managed by endoscopic hemostasis. These findings demonstrate that endoscopic papillectomy is a clinically effective and safe therapeutic option for duodenal papillary adenoma, particularly when combined with targeted stent placement and immediate hemostatic intervention.
This study investigated the association between ERBB2 amplification and mismatch repair (MMR) status in gastric adenocarcinoma, and evaluated their impact on tumor differentiation, PD-L1 expression, and prognosis. One hundred and seventy six patients from the First People's Hospital of Changzhou (Changzhou, China) were retrospectively analyzed. ERBB2 amplification was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), with positivity defined as an ERBB2/CEP17 ratio >= 2.0. MMR deficiency (dMMR) was determined by loss of MLH1, MSH2, MSH6, and/or PMS2 protein expression. PD-L1 expression was quantified using the Combined Positive Score (CPS) via the 22C3 pharmDx assay. Survival analysis employed Kaplan-Meier curves with log-rank testing. Among the cohort, 26/176 patients (14.8%) were ERBB2-positive and 22/176 (12.5%) exhibited dMMR, with no significant association. ERBB2 amplification correlated with specific tumor differentiation patterns, while dMMR was associated with female sex, moderate differentiation, and elevated PD-L1 expression. Kaplan-Meier analysis demonstrated significantly improved survival in the PD-L1-positive group, indicating PD-L1 positivity as a predictor of survival benefit. Combined assessment of ERBB2 and MMR status may optimize therapeutic strategies for gastric adenocarcinoma.
Organoid systems are capable of forming three-dimensional self-organizing structures that closely recapitulate the cellular composition and physiological functions of native gastric tissue. Since their introduction, gastric organoid technology has rapidly advanced and become a powerful tool for studying gastric development, disease mechanisms, and therapeutic responses. This review summarizes key developments in the field, with a focus on five major areas of application: gastric developmental biology, modeling of Helicobacter pylori infection, research on gastric cancer and drug resistance, assessment of personalized therapy, and regenerative medicine. Distinct from previous reviews, this article systematically traces the evolution of gastric organoid technology and provides an in-depth analysis of current limitations in microenvironment reconstruction, standardized culture, immune co-culture modeling, and clinical translation. In addition, it discusses emerging strategies and integrated technologies aimed at overcoming these challenges, offering perspectives to advance organoid systems from basic research toward clinical application.
This study aimed to explore the diagnostic value of carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and neurone-specific enolase (NSE) in rectal neuroendocrine tumors (rNETs). A total of 261 rNETs patients admitted to Nanjing Hospital of Traditional Chinese Medicine and Jiangsu Province Hospital from January 2021 to December 2024 were collected. Among rNETs patients with varying pathological grades, the differences in gender, age, and NSE levels were statistically significant. Aged females and elevated levels of NSE were identified as risk factors for predicting G2/G3 rNETs. Among rNETs patients with and without metastasis, the differences in gender, age, CEA, and NSE levels were statistically significant. Aged females and elevated levels of NSE were identified as risk factors for predicting rNETs metastasis. Binary logistic regression analysis was conducted to derive joint prediction models to predict the grade and metastasis of rNETs. The areas under the curve (AUCs) for age and NSE in predicting grade were 0.626 and 0.708, respectively, both lower than the AUC (0.756) of the model. The AUCs for age and NSE in predicting metastasis were 0.723 and 0.757, respectively, both lower than the AUC (0.847) of the model. In conclusion, NSE demonstrates notable diagnostic value for predicting the grade and metastasis of rNETs.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are highly heterogeneous neoplasms of the gastrointestinal tract and pancreas. The objective of this study was to develop and verify a prediction nomogram for determining the overall survival rate of stage IV GEP-NENs. Data from 2139 stage IV GEP-NENs patients between 2010 and 2017 were extracted from the SEER database. Concordance index (C-index), calibration curve analysis, receiver operating curve (ROC) analysis, and decision curve analysis (DCA) were used to evaluate and validate the predictive performance of the nomogram. The difference in survival rates between the low-risk and high-risk groups was analyzed using the Kaplan-Meier method. Ten risk factors were integrated into the prognostic nomogram. The C-index (0.7961 in the training set and 0.801 in the validating set) and calibration curve analysis exhibited an excellent consistency between the two groups. The AUC value was 0.879, 0.857, and 0.839, respectively, for nomograms predicting 1-, 3-, and 5-year overall survival in the training set. In the validation set, AUC values were 0.859, 0.844, and 0.831 for nomograms predicting 1-, 3-, and 5-year overall survival. According to the DCA analysis, the nomogram offered significant clinical benefits. The scatter plot of risk score demonstrated that with the increase in risk score, the proportion of death also increased. In both training and validation sets, the Kaplan-Meier analysis displayed that patients in the high-risk group with stage IV GEP-NENs had a worse overall survival rate than patients in the low-risk group. A prognostic nomogram of stage IV GEP-NENs was established by integrating age, sex, differentiation, primary site, tumor size, surgery, chemotherapy, and bone, brain, and lung metastases. With further verification, the nomogram with favorable specificity, sensitivity, and added clinical benefit could help clinicians assess prognosis and provide treatment guidance for stage IV GEP-NENs patients.
Endoscopic treatment is widely used for T1 colorectal cancer, yet there are limited studies that compare the survival outcomes of patients treated with endoscopy and surgery. This study utilized the data from the Surveillance, Epidemiology, and End Results database to evaluate the long-term survival of the two treatment regimens in America. The analysis of T1-stage colorectal cancer patients from 2000 to 2018 was assessed using Kaplan-Meier analyses and log-rank tests. Accounting for the imbalance in covariate distribution between the two groups, a propensity score matching method was employed, followed by a comparison of survival outcomes. Of the 4,834 patients included in this study, 4,116 underwent surgery, while 718 underwent endoscopic procedures. Overall survival did not significantly differ between the groups prior to the use of the propensity score matching method, but the surgery group's cancer-specific survival was noticeably higher (p = 0.0022). Following propensity score matching, there were no discernible variations in overall or cancer-specific survival. Subgroup analysis indicated that older patients, males, and those with higher histological grades had significantly better cancer-specific survival outcomes with surgery compared to endoscopic treatment. According to data from the American population, there was no variation in long-term survival rates for T1-stage colorectal cancer between the two groups.
