Gastroenterology Report最新文献

{"title":"Current status of serum metabolites biomarkers for polyps and colorectal cancer: a systematic review.","authors":"Maryam Fatimah Abu Bakar, Azmawati Mohammed Nawi, Siok Fong Chin, Suzana Makpol","doi":"10.1093/gastro/goae106","DOIUrl":"10.1093/gastro/goae106","url":null,"abstract":"<p><strong>Background: </strong>Early detection of colorectal cancer (CRC) is crucial to enhance the disease treatment and prognosis of patients. Colonoscopy remains the gold standard for CRC detection; however, it requires trained personnel with expensive tools. Currently, serum metabolites have been discovered to be used to discriminate patients with polyps and CRC. This study aimed to identify the most commonly detected predictive serum metabolites for polyps and CRC.</p><p><strong>Methods: </strong>A systematic search of the Web of Science, PubMed, and Cochrane Library databases was conducted using PRISMA guidelines. Ten studies investigating serum metabolite biomarkers of CRC and polyps using different analytical platforms and study populations were included. QUADOMICS tool was used to analyse the quality of the included studies. All reported metabolites were then enriched into the pathways using MetaboAnalyst 5.0.</p><p><strong>Results: </strong>We found that several potential signature metabolites overlapped between studies, including tyrosine, lysine, cystine, arabinose, and lactate for CRC and lactate and glutamate for polyps. The most affected pathways related to CRC were the urea cycle, glutathione metabolism, purine metabolism, glutamate metabolism, and ammonia recycling. In contrast, those affected in the polyps were the urea cycle, glutamate metabolism, glutathione metabolism, arginine and proline metabolism, and carnitine synthesis.</p><p><strong>Conclusions: </strong>This review has found commonly detected serum metabolites for polyps and CRC with huge potential to be used in clinical settings. However, the differences between altered pathways in polyps and CRC, other external factors, and their effects on the regulation level, sensitivity, and specificity of each identified metabolite remained unclear, which could benefit from a further extensive cohort study and well-defined analysis equipment.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae106"},"PeriodicalIF":3.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"¹⁸F-FAPI-42 PET/CT enhances the diagnostic efficacy for peritoneal metastasis of colorectal cancer and guides treatment decisions: an original retrospective study.","authors":"Xuneng Zhang, Rongqin Zhang, Qingyang Zheng, Zichuan He, Bing Lan, Yun Zhong, Zhichao Huang, Wei Fan, Hui Wang, Keli Yang, Zhanwen Zhang, Huaiming Wang","doi":"10.1093/gastro/goae104","DOIUrl":"10.1093/gastro/goae104","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is the third-most common type of cancer. When peritoneal metastasis (PM) develops, diagnosing metastatic lesions is difficult and the prognosis is poor. This study aimed to compare the value of fluorine-18 fibroblast activation protein-specific inhibitor (¹⁸F-FAPI-42) and fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting PM of colorectal cancer and to guide clinical decision-making.</p><p><strong>Methods: </strong>Forty-eight patients with PM who underwent both ¹⁸F-FAPI-42 and ¹⁸F-FDG PET/CT examinations were studied. The maximum standardized uptake value (SUV max), tumor-to-background ratios (TBRs) and peritoneal cancer index (PCI) of the PM were compared between the two imaging techniques. The intraclass correlation coefficient (ICC) was used to compare the consistency between the PET/CT PCI score and the intraoperative PCI. A receiver-operating characteristic curve was used to predict the accuracy of CC-0 cytoreduction (complete cytoreduction with no visible disease).</p><p><strong>Results: </strong>The sensitivity and accuracy of ¹⁸F-FAPI-42 PET/CT for detecting PM were higher than those of ¹⁸F-FDG PET/CT (82.1% vs 61.1%, <i>P </i><<i> </i>0.01; 84.6% vs 74.5%, <i>P </i><<i> </i>0.01). The median SUV max and TBR of PM was greater in ¹⁸F-FAPI-42 than in ¹⁸F-FDG PET/CT [4.8 (1.9-20.1) vs 4.7 (1.0-11.0), <i>P </i>=<i> </i>0.02; 4.3 (1.4-14.6) vs 2.9 (0.6-8.0), <i>P </i><<i> </i>0.01, respectively]. The median PCI of PM based on ¹⁸F-FAPI-42 PET/CT was greater than that based on ¹⁸F-FDG PET/CT (15 vs 9, <i>P </i><<i> </i>0.01). The ICC for ¹⁸F-FAPI-42 PCI was greater than that for ¹⁸F-FDG PCI (0.915 vs 0.724, <i>P </i><<i> </i>0.01). The cut-off values of the PCI of the PM for ¹⁸F-FAPI-42 and ¹⁸F-FDG PET/CT to predict CC-0 were <18 and <10, with areas under the curve of 0.80 and 0.79, respectively.</p><p><strong>Conclusions: </strong>¹⁸F-FAPI-42 PET/CT has superior diagnostic efficacy for PM, particularly in the right upper epigastrium and small intestine. The PCI score of ¹⁸F-FAPI-42 PET/CT is very close to the intraoperative PCI score and has a high value for predicting CC-0. The individualized management of PM based on the ¹⁸F-FAPI-42 PET/CT PCI score is pivotal.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae104"},"PeriodicalIF":3.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The benefit of surgery during systematic therapy for gastrointestinal stromal tumor liver metastasis: a SEER-based retrospective study.","authors":"Bozhi Hu, Yingjiang Ye, Zhidong Gao","doi":"10.1093/gastro/goae095","DOIUrl":"10.1093/gastro/goae095","url":null,"abstract":"<p><strong>Background: </strong>The liver is the most common site of gastrointestinal stromal tumor (GIST) metastasis. Most patients who develop metastases gradually develop multiline drug resistance during long-term systematic treatment. We aimed to evaluate the benefit of surgery during the systematic treatment of GIST liver metastases.</p><p><strong>Methods: </strong>Data on GISTs with liver metastasis were retrieved from the Surveillance, Epidemiology, and End Results database. This study included 607 patients, of whom 380 patients were treated with chemotherapy alone (Chemo group) and 227 patients underwent surgery in addition to chemotherapy (Chemo&Surg group). The primary outcomes were cancer-specific survival (CSS) and overall survival (OS). Propensity score matching (PSM) was performed to balance the baseline factors.</p><p><strong>Results: </strong>According to the multivariate analysis, surgery benefitted both CSS and OS (<i>P </i><<i> </i>0.001). After PSM, surgical resection still showed significant benefits in terms of both CSS and OS (<i>P </i><<i> </i>0.001). Surgery combined with chemotherapy increased the median CSS by at least 63 months and the median OS by at least 76 months. Subgroup analysis of the Chemo&Surg group revealed that the timing of surgery was not an independent influencing factor for either CSS or OS.</p><p><strong>Conclusions: </strong>We found that performing additional surgery, in addition to systematic therapy, for GIST liver metastasis resulted in improved CSS and OS. These benefits were not affected by the timing of surgery during systemic treatment.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae095"},"PeriodicalIF":3.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation: a randomized, double-blind, placebo-controlled pilot clinical trial.","authors":"Ana Terrén Lora, Bruno F Penadés, Sara López Oliva, Sari Arponen, Gülşah Okutan, Guerthy Melissa Sánchez Niño, Ismael San Mauro Martín","doi":"10.1093/gastro/goae101","DOIUrl":"https://doi.org/10.1093/gastro/goae101","url":null,"abstract":"<p><strong>Background: </strong>Functional constipation includes a set of gastrointestinal symptoms unexplainable by an identifiable underlying physical cause or pathology. The prevalence of this condition is high and there is a need to develop strategies to reduce it. Probiotics, prebiotics, and synbiotics may be an alternative treatment for chronic functional constipation.</p><p><strong>Methods: </strong>To compare the efficacy of dietary supplementation on symptoms of patients who suffer from chronic functional constipation. An exploratory, randomized, double-blind, placebo-controlled pilot clinical trial was conducted with 74 patients diagnosed with chronic functional constipation who were divided into four treatment groups-Group A: probiotics; Group B: prebiotics; Group C: synbiotics; Group D: placebo. Each patient was treated for 8 weeks. At the beginning and end of treatment, data were collected by administering questionnaires and scales, including the Bristol stool scale, on gastrointestinal symptoms, bowel movements, and sociodemographic and anthropometric characteristics.</p><p><strong>Results: </strong>Stool frequency increased in all four study groups, and greatest difference was observed in the synbiotics group (2.8 ± 1.3 vs. 5.9 ± 2.6; <i>P</i> < 0.001). Stool consistency improved only in the active treatment groups. Based on the evaluation of gastrointestinal symptoms, participants treated with prebiotics, probiotics and synbiotics showed the greatest improvement in abdominal pain (8.28 ± 2.63 vs. 6.56 ± 2.62; <i>P</i> = 0.009), gastroesophageal reflux (4.60 ± 2.66 vs. 3.45 ± 2.42; <i>P</i> = 0.039) and constipation symptoms (13.00 ± 3.97 vs. 8.71 ± 3.35; <i>P</i> = 0.003), respectively. As for quality of life, the main changes were observed in physical health domains, with a placebo effect.</p><p><strong>Conclusions: </strong>The present study provides evidence supporting the efficacy of dietary supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation after 8 weeks of treatment.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae101"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TNFSF15</i> variant predicts disease progression in Chinese patients with Crohn's disease.","authors":"Qi Zhang, Wei Wang, Bingjie Xiang, Dezheng Lin, Jun Hu, Junzhang Zhao, Jue Lin, Tao Liu, Jun Deng, Min Zhang, Min Zhi","doi":"10.1093/gastro/goae103","DOIUrl":"https://doi.org/10.1093/gastro/goae103","url":null,"abstract":"<p><strong>Background: </strong>The genetic variant of tumor necrosis factor superfamily member 15 (<i>TNFSF15</i>) is associated with Crohn's disease (CD) and the development of intestinal fibrosis and stricturing. We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.</p><p><strong>Methods: </strong>We genotyped the single nucleotide polymorphism rs6478109 within the <i>TNFSF15</i> gene in 428 CD patients and 450 health controls to assess its association with CD. Genotype-phenotype correlation analyses were performed. Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.</p><p><strong>Results: </strong>The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls (63.3% vs. 46.7%, <i>P </i><<i> </i>0.001). Patients with GG genotype were more predisposed to develop the stricturing phenotype, compared with those with AA + AG genotypes with a hazard ratio of 1.426 (95% confidence interval: 1.029-1.977, <i>P </i>=<i> </i>0.033). This trend was similarly observed in patients utilizing biological agents, with a hazard ratio of 4.396 (95% confidence interval: 1.780-10.854, <i>P </i>=<i> </i>0.001). Furthermore, increased TL1A, pro-fibrotic proteins, and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.</p><p><strong>Conclusions: </strong>The <i>TNFSF15</i> risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae103"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New perspectives in liver diseases with challenges.","authors":"Calvin Q Pan, Nancy Reau","doi":"10.1093/gastro/goae098","DOIUrl":"https://doi.org/10.1093/gastro/goae098","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae098"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review and update on acute severe lower gastrointestinal bleeding in Crohn's disease: a management algorithm.","authors":"Tong Tu, Mengqi Chen, Zhirong Zeng, Jianming Lin, Luohai Chen, Caiguang Liu, Xiaojun Zhuang","doi":"10.1093/gastro/goae099","DOIUrl":"https://doi.org/10.1093/gastro/goae099","url":null,"abstract":"<p><p>Acute severe lower gastrointestinal bleeding is a rare but potentially fatal complication of Crohn's disease (CD), affecting between 0.6% and 5.5% of CD patients during their lifelong disease course. Managing bleeding episodes effectively hinges on vital resuscitation. Endoscopic evaluation and computed tomography play crucial roles in accurate identification and intervention. Fortunately, most bleeding episodes can be successfully managed through appropriate conservative treatment. Medical therapies, particularly infliximab, aim to induce and maintain mucosal healing and serve as the leading treatment approach. Minimally invasive procedures, such as endoscopic hemostasis and angio-embolization, can achieve immediate hemostasis. Surgical treatment is only considered a last resort when conservative therapies fail. Despite achieving hemostasis, the risk of rebleeding ranges from 19.0% to 50.5%. The objective of this review is to provide a comprehensive and updated overview of the clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic outcomes associated with acute severe gastrointestinal bleeding in CD. Furthermore, we aimed to propose a management algorithm to assist clinicians in the effective management of this condition.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae099"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gasdermin E mediates pyroptosis in the progression of hepatocellular carcinoma: a double-edged sword.","authors":"Yan Lu, Junnv Xu, Haifeng Lin, Mingyue Zhu, Mengsen Li","doi":"10.1093/gastro/goae102","DOIUrl":"https://doi.org/10.1093/gastro/goae102","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. It usually develops due to viral hepatitis or liver cirrhosis. The molecular mechanisms involved in HCC pathogenesis are complex and incompletely understood. Gasdermin E (<i>GSDME</i>) is a tumor suppressor gene and is inhibited in most cancers. Recent studies have reported that, unlike those in most tumors, GSDME is highly expressed in liver cancer, and GSDME expression in HCC is negatively associated with prognosis, suggesting that GSDME may promote HCC. However, antitumor drugs can induce pyroptosis through GSDME, killing HCC cells. Therefore, GSDME may both inhibit and promote HCC development. Because functional studies of GSDME in HCC are limited, the precise molecular mechanisms of GSDME in liver cancer remain unclear. In this article, we have reviewed the role, related mechanisms, and clinical importance of GSDME at the onset and development of HCC to provide a theoretical foundation to improve the clinical diagnosis and treatment of liver cancer.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae102"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the management of alcohol-associated liver disease.","authors":"Ahmad Anouti, Thomas A Kerr, Mack C Mitchell, Thomas G Cotter","doi":"10.1093/gastro/goae097","DOIUrl":"10.1093/gastro/goae097","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae097"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of RelA/p65 Ser536 inhibits the progression and metastasis of hepatocellular carcinoma by mediating cytoplasmic retention of NF-κB p65.","authors":"Wentao Zuo, Haoyang Ma, Jianghui Bi, Tiaolan Li, Yifeng Mo, Shiyu Yu, Jia Wang, Beiqing Li, Jinfeng Huang, Yongwen Li, Li Li","doi":"10.1093/gastro/goae094","DOIUrl":"10.1093/gastro/goae094","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic and extrahepatic metastases contribute to the high recurrence rate and mortality of hepatocellular carcinoma (HCC). Constitutive activation of nuclear factor-κB (NF-κB) is a crucial feature of HCC. NF-κB p65 (p50-p65) is the most common dimeric form. Ser536 acts as an essential phosphorylation site of RelA/p65. However, the effect of RelA/p65 Ser536 phosphorylation on progression and metastases during intermediate and advanced HCC has not been reported.</p><p><strong>Methods: </strong>Phosphorylation of RelA/p65 (p-p65 Ser536) and NF-κB p65 were detected by using immunohistochemical staining in HCC tissue samples. The biological effects of RelA/p65 Ser536 phosphorylation were evaluated by using xenograft and metastasis models. NF-κB p65 nuclear translocation was detected by using Western blotting. The binding of NF-κB p65 to the <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i> promoters was detected by using chromatin immunoprecipitation. The biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition were assessed by using tetrazolium-based colorimetry, colony formation, EdU incorporation, flow cytometry, cell wound healing, and transwell assay.</p><p><strong>Results: </strong>NF-κB p65 is highly expressed, while p-p65 Ser536 is not well expressed in intermediate and advanced HCC tissues. <i>In vivo</i> experiments demonstrated that a phosphorylation-mimetic mutant of RelA/p65 Ser536 (p65/S536D) prevents tumor progression and metastasis. <i>In vitro</i> experiments showed that p65/S536D inhibits proliferation, migration, and invasion. Mechanistically, RelA/p65 Ser536 phosphorylation inhibits NF-κB p65 nuclear translocation and reduces NF-κB p65 binding to the <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i> promoters.</p><p><strong>Conclusions: </strong>RelA/p65 Ser536 phosphorylation was detrimental to NF-κB p65 entry into the nucleus and inhibited HCC progression and metastasis by reducing <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i>. The phosphorylation site of RelA/p65 Ser536 has excellent potential to be a promising target for NF-κB-targeted therapy in HCC.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"12 ","pages":"goae094"},"PeriodicalIF":3.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}