Wei Tang, Makeda Dawkins, Anila Kumar, Mohammed Nasereldin, Gabriel Heering, Morgan Soffler, David C Wolf
{"title":"Case Report: Management of intracranial hypertension in acute-on-chronic liver failure: a case of fulminant cerebral edema and acute-onset severe hyperammonemia in a patient with cirrhosis.","authors":"Wei Tang, Makeda Dawkins, Anila Kumar, Mohammed Nasereldin, Gabriel Heering, Morgan Soffler, David C Wolf","doi":"10.3389/fgstr.2025.1542588","DOIUrl":"https://doi.org/10.3389/fgstr.2025.1542588","url":null,"abstract":"<p><p>Intracranial hypertension (ICH) is a well-recognized and potentially fatal complication of acute liver failure. It is rarely observed in patients with chronic liver disease or acute-on-chronic liver failure (ACLF). Only a few studies have investigated the management of ICH in ACLF. Here, we present an uncommon case of acute-onset severe hyperammonemia in a patient with cirrhosis who developed fulminant ICH. Rapid institution of renal placement therapy and therapeutic plasma exchange achieved a dramatic reduction in the serum ammonia level, but did not slow the patient's rapid neurological deterioration.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":"1542588"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colorectal lymph node harvest in cancer surgery, adequacy and treatment implication: a 5-year retrospective analysis from a tertiary hospital in Ethiopia.","authors":"Sirna Emana Jaleta, Abdo Kedir Abafogi, Tamirat Godebo Woyimo, Gashahun Mekonnen Disassa, Sultan Jebel Usman, Abduletif Haji-Ababor Abagojam, Kedir Negesso Tukeni","doi":"10.3389/fgstr.2025.1503842","DOIUrl":"https://doi.org/10.3389/fgstr.2025.1503842","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer is one of the common malignancies, and obtaining sufficient lymph nodes after surgeries is critical for staging and subsequent treatment planning. While guidelines advocate collecting at least 12 lymph nodes, insufficient lymph node sampling can have catastrophic consequences.</p><p><strong>Methods: </strong>This was a retrospective study that looked at the parameters influencing lymph node retrieval during colorectal cancer surgery in one of tertiary hospital in Ethiopia. In this study, data from 85 patients' records for stages I-III were analyzed and divided into two groups: adequately harvested and inadequately harvested. The association between potential factors impacting optimal harvests was analyzed.</p><p><strong>Results and discussion: </strong>The study found that the majority of cancer patients were between the ages of 34 and 53 years, in which the adequate lymph node retrieval was achieved only in 23% of cases. Procedures being performed by GI oncologic surgeons (P = 0.006, AOR;26.4), depth of invasion (AOR:14. P = 0.05), and length of specimen (AOR:5.365 P:0.045) were associated with improved adequacy of harvesting the lymph node. In conclusion, the study discovered that colorectal cancer primarily affects young people. Only a small number of participants had adequate lymph nodes harvested. The operating surgeon's expertise, tumor characteristics, and specimen lengths were the most important elements influencing lymph node retrieval in colorectal cancer surgery in the setting. Adequate sample length, combined with better availability to more qualified operators, may improve the adequacy of harvest in guiding future treatment decisions.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":"1503842"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diogo Alpuim Costa, Pedro Barata Coelho, Conceição Calhau, Ana Faria
{"title":"Editorial: Gut microbiota in health and disease.","authors":"Diogo Alpuim Costa, Pedro Barata Coelho, Conceição Calhau, Ana Faria","doi":"10.3389/fgstr.2025.1568509","DOIUrl":"https://doi.org/10.3389/fgstr.2025.1568509","url":null,"abstract":"","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":"1568509"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liwei Zhuang, Junnan Li, Yu Zhang, Shibo Ji, Huichun Xing
{"title":"Real-world effectiveness of sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir against genotype 3 hepatitis C virus infection: a systematic review and meta-analysis.","authors":"Liwei Zhuang, Junnan Li, Yu Zhang, Shibo Ji, Huichun Xing","doi":"10.3389/fgstr.2025.1511150","DOIUrl":"https://doi.org/10.3389/fgstr.2025.1511150","url":null,"abstract":"<p><strong>Introduction: </strong>Direct antiviral agents (DAAs) have dramatically changed the landscape of liver diseases associated with chronic hepatitis C virus (HCV) infection. However, limited data are available on the antiviral effect of sofosbuvir (SOF) + velpatasvir (VEL) ± ribavirin (RBV), SOF + VEL + voxilaprevir (VOX), and glecaprevir (GLE) + pibrentasvir (PIB) in treating patients infected with HCV GT3 in a real-world setting.</p><p><strong>Methods: </strong>Using the EMBASE, PubMed, and Cochrane Library databases, articles were screened from 1 January 2016 to 1 June 2024. The sustained virologic response (SVR) rates were analyzed using the Freeman-Tukey double arcsine transformation in a random-effects model in R4.1.0 software.</p><p><strong>Results: </strong>We recruited 3,177 patients with HCV GT3 in 19 studies from 9 countries. The pooled SVR12/24 rate of the three evaluated regimens was 94.00% (95% CI: 90.87-96.59%). Furthermore, the SVR rate was 83.81% (95% CI: 75.70-90.62%) in patients receiving SOF+VEL+VOX; 94.98% (95% CI: 92.02-97.33%) in patients receiving SOF+VEL ± RBV; and 96.96% (95% CI: 93.20-99.45%) in patients receiving GLE+PIB. The pooled SVR12/24 rate of the three regimens was 95.70% (95% CI: 91.74-98.58%) and 90.50% (95% CI: 83.50-95.90%) in non-cirrhotic and cirrhotic patients, respectively. The pooled SVR rate was 96.79% (95% CI: 93.37-99.13%) and 88.41% (95% CI: 82.67-93.22%) in treatment-naive and treatment-experienced patients, respectively.</p><p><strong>Conclusion: </strong>SOF+VEL ± RBV, GLE+PIB, and SOF+VEL+VOX had good antiviral effectiveness for chronic HCV-GT3 infection in real-world settings. Factors such as cirrhosis and treatment experience, especially previous DAA treatment failure, may influence the SVR rate.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":"1511150"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolena Trocchia, Maua Mosha, Bailey Hamner, Neil Goldenberg, Racha Khalaf
{"title":"Prevalence and characteristics of gastrointestinal disorders, medication use, and diagnostic interventions in pediatric patients with cystic fibrosis: a nested case-control analysis from the TriNetX EMR-derived global research network real-world dataset.","authors":"Carolena Trocchia, Maua Mosha, Bailey Hamner, Neil Goldenberg, Racha Khalaf","doi":"10.3389/fgstr.2024.1489876","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1489876","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal (GI) disease in pediatric patients with cystic fibrosis (CF) is a growing concern in the era of improved lung disease; however, the true prevalence of GI diagnoses, medical therapies, and frequency of diagnostic and therapeutic interventions in this population have yet to be explored on a multisystem scale. The aim of the present study was to describe, among pediatric patients with CF (PwCF) compared to a large cohort of healthy controls, the prevalence and types of 1) GI disorders; 2) GI medication use; and 3) GI procedural interventions.</p><p><strong>Methods: </strong>This was a multicenter case-control analysis using the TriNetX electronic medical record (EMR) global anonymized data platform. Patients were included if they had an ICD9/10 diagnosis code and were between the age of zero to ≤ 21 years between January 1st, 2010, and January 1st, 2020. Those with a history of solid organ transplants were excluded.</p><p><strong>Results: </strong>The cohort was comprised of 7,649 patients with a diagnosis of CF (cases) and 22,516,240 patients without CF (controls). The prevalence of any GI disorder was greater in pediatric PwCF compared to those without CF (73% versus <1%). The prevalence of diseases of the biliary tract and pancreas (43% vs. <1%; <i>p</i><.0001), hepatic disease (8.8% vs. <1%; <i>p</i><.0001), disease of the esophagus to duodenum (34% vs. <1%; <i>p</i><.0001), and intestinal disease (43% vs. <1%; <i>p</i><.0001) were each significantly greater in PwCF (<i>p</i><0.0001). Furthermore, the frequencies of esophagogastroduodenoscopy (EGD), colonoscopy and endoscopic retrograde cholangiopancreatography (ERCP) were significantly higher among PwCF than controls (9.5% vs. <1%; 2.8%% vs. <1%; and 0.3% vs <.001% respectively; <i>p</i><0.0001 for all comparisons).</p><p><strong>Conclusion: </strong>The prevalence of GI diagnoses, use of GI medications, and frequency of GI procedures are all higher among pediatric patients PwCF. Prospective multicenter studies are warranted to substantiate these findings, further investigate risk factors for GI disorders, and to describe potential changes in GI disorders with novel CF disease-modifying therapies.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"3 ","pages":"1489876"},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirsten Boonstra, Lisanne M D Pattynama, Yasmijn J van Herwaarden, Wietse J Eshuis, Roos E Pouw
{"title":"Endoscopic vacuum therapy in the upper gastrointestinal tract.","authors":"Kirsten Boonstra, Lisanne M D Pattynama, Yasmijn J van Herwaarden, Wietse J Eshuis, Roos E Pouw","doi":"10.3389/fgstr.2024.1502682","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1502682","url":null,"abstract":"<p><p>Endoscopic vacuum therapy (EVT) is a promising and versatile intervention for managing transmural defects in the upper gastrointestinal tract. Despite challenges, EVT exhibits great efficacy and safety, emphasizing the need for standardized protocols and evidence-based practices. We provide an overview, including mechanism, indications, types of EVT devices and complications, guiding clinicians in decision-making. Common challenges in EVT are highlighted, facilitating adequate implementation of EVT and helping to avoid common mistakes in daily practice.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"3 ","pages":"1502682"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Subhepatic appendicitis in a 27-year-old male: a case report from Odahulle General Hospital of Ethiopia.","authors":"Abduletif Haji Ababor Abagojam, Remedan Jemal Dekema, Tamirat Godebo Woyimo, Jafer Yasin Mohammed, Kedir Negesso Tukeni","doi":"10.3389/fgstr.2024.1503818","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1503818","url":null,"abstract":"<p><p>The appendix is a small, tube-shaped organ that connects to the cecum, the beginning of the large intestine. Though its role is unknown, it can become infected, resulting in acute appendicitis, which, if not detected and treated early, can lead to serious consequences. Though the symptoms and signs of acute appendicitis are straightforward in most cases, atypical locations might result in unexpected presentations, which can lead to complications as it might not be detected and treated early. This case report describes a 27-year-old Black Ethiopian male patient who presented with right upper abdominal pain, low-grade fever, palpitations, and diarrhea. He also had some episodes of vomiting of ingested matter. Upon physical examination, the patient appeared acutely sick with some degree of tachycardia. An abdominal examination revealed right upper abdominal quadrant tenderness, though there was no palpable mass noted. Laboratory investigations were unremarkable apart from the stool examinations which revealed many pus and red blood cells and was full of actively motile bacteria. An abdominal ultrasound showed an enlarged subhepatic appendix with an internal fecalith 1 cm in depth, that was partially compressible, with no obvious peri appendiceal free fluid or other pathology. An assessment of subhepatic acute appendicitis was suspected and an emergency operation was conducted which revealed an inflamed subhepatic appendix that was on the verge of rupture. At a subsequent follow-up, the patient had significantly improved as evidenced by the lack of symptoms including abdominal pain, fever, and palpitation. Subhepatic appendix is a rare condition caused by either the non-descent of the cecum or intestinal malrotation during early development. As its presentation is not classical and hence mimics other pathologies, the diagnosis may be overlooked, resulting in perforation and abscess formation and leading to increased morbidity and possibly mortality. A high level of suspicion is required for early diagnosis and treatment to improve patient outcomes.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"3 ","pages":"1503818"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anastasios Mpountouridis, Christina Tsigalou, Ioanna Bezirtzoglou, Eugenia Bezirtzoglou, Elisavet Stavropoulou
{"title":"Gut microbiome in non-alcoholic fatty liver disease.","authors":"Anastasios Mpountouridis, Christina Tsigalou, Ioanna Bezirtzoglou, Eugenia Bezirtzoglou, Elisavet Stavropoulou","doi":"10.3389/fgstr.2024.1534431","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1534431","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) has a rapidly growing incidence worldwide, affecting approximately one-third of world population. The disturbance of gut commensal bacteria impacting host's homeostasis is referred to as gut dysbiosis. The gut microbiome contributes to the pathogenesis of NAFLD through various pathways. Gut microbiota is at constant interactions with the intestinal epithelial barrier and affects its integrity. Through gut-liver axis, gut microbiota may influence liver immune function. The release of lipopolysaccharides (LPS) from intestines to portal vein which are transported to the liver, may trigger hepatic inflammation, steatosis and even fibrosis. Moreover, the gut microbiome induces the conversion of primary bile acids (BAs) to secondary BAs, which activates intestinal receptors, such as FXR and TGR5. FXR activation decreases fat absorption and thus reduces hepatic lipid accumulation, while TGR5 activation promotes the release of glucagon-like peptide-1 (GLP-1) in blood. Furthermore, gut ethanol-producing bacteria has been implicated in NAFLD development. Additionally, in NAFLD there is a reduction in intestinal levels of short-chain fatty acids, such as butyrate, propionate and acetate. Many bacterial alterations have been observed in NAFLD, including the increased <i>Bacteroidetes</i> and decreased <i>Firmicutes</i>. Many probiotics have been tried in NAFLD prevention and management, including a plethora of strains from <i>Lactobacilli</i>, <i>Bifidobacteria</i> and <i>Streptococcus</i> and some of them have promising perspectives. There is also some promising data from the administration of prebiotics (such as inulin and fructo-oligosaccharides) and symbiotics (probiotics plus prebiotics). Faecal microbiota transplantation (FMT) is yet to be evaluated for its efficacy against NAFLD.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"3 ","pages":"1534431"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco J Barrera Flores, José Adrián Guerrero Tamez, Tatiana Winkelman, Regina Barrera Flores, Elizabeth N Madva
{"title":"A multidisciplinary approach to the management of disorders of gut-brain interaction: psychopharmacology, psychotherapy, and diet.","authors":"Francisco J Barrera Flores, José Adrián Guerrero Tamez, Tatiana Winkelman, Regina Barrera Flores, Elizabeth N Madva","doi":"10.3389/fgstr.2025.1637172","DOIUrl":"10.3389/fgstr.2025.1637172","url":null,"abstract":"<p><strong>Introduction: </strong>Disorders of gut-brain interaction (DGBI), including irritable bowel syndrome and functional dyspepsia, are chronic gastrointestinal syndromes characterized by visceral hypersensitivity and altered brain-gut signaling in the absence of known structural pathology. A significant proportion of individuals with DGBI have comorbid psychiatric conditions, especially anxiety and depression, highlighting the biopsychosocial underpinnings of these disorders.</p><p><strong>Methods: </strong>This narrative review synthesizes the neurophysiological, psychological, pharmacological, and psychotherapeutic literature related to DGBI. We examined the role of gut-brain axis dysregulation, the prevalence and impact of psychiatric comorbidity, and evaluated current treatment modalities, including neuromodulators, brain-gut behavior therapies (BGBTs), and dietary interventions.</p><p><strong>Results: </strong>Neuroimaging and genetic studies support the role of emotional and cognitive circuits in modulating gut sensitivity and symptom perception. Psychiatric comorbidity, particularly anxiety, is bidirectionally linked to DGBI and influences treatment response. Neuromodulators such as tricyclic antidepressants demonstrate modest efficacy. BGBTs-including cognitive behavioral therapy and gut-directed hypnotherapy-exhibit comparable efficacy to pharmacologic treatments, with sustained symptom relief and additional benefit on mood and illness-related beliefs.</p><p><strong>Discussion: </strong>DGBI represent complex, stress-sensitive conditions best managed through multidisciplinary care. Integration of pharmacologic neuromodulation, psychotherapeutic interventions, and dietary strategies targeting the brain-gut axis offers the most comprehensive approach. Future research should refine treatment matching based on symptom phenotype, psychological profile, and gut-brain biomarkers to improve long-term outcomes.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dimitri F Joseph, Andrew Fu, Ricardo E Flores, Dev V Sharma, Joseph F LaComb, Julie M Clark, Ellen Li, Yunhan Liao, Jie Yang, Qi Yu, Seidu Adams, Olorunseun O Ogunwobi, Brian Theisen, Nina G Steele, Bin Chen, Alexandra Guillaume
{"title":"The effect of African ancestry and mismatch-repair enzyme deficiency/microsatellite instability-high on colorectal adenocarcinoma immune gene expression.","authors":"Dimitri F Joseph, Andrew Fu, Ricardo E Flores, Dev V Sharma, Joseph F LaComb, Julie M Clark, Ellen Li, Yunhan Liao, Jie Yang, Qi Yu, Seidu Adams, Olorunseun O Ogunwobi, Brian Theisen, Nina G Steele, Bin Chen, Alexandra Guillaume","doi":"10.3389/fgstr.2025.1638438","DOIUrl":"10.3389/fgstr.2025.1638438","url":null,"abstract":"<p><strong>Background: </strong>Previous analyses of bulk colon and rectal adenocarcinoma (COAD/READ) RNA-sequence data comparing African ancestry (AA) and European ancestry (EA) groups have reported differentially expressed genes related to the immune response. However, these previous analyses of AA versus EA tissues did not control for mismatch-repair enzyme (MMR)/microsatellite instability (MSI) status, which is also associated with altered expression of immune related genes, and is used to determine eligibility for immune checkpoint inhibitor therapy.</p><p><strong>Methods: </strong>TCGA-COAD-READ bulk RNA-sequence data were analyzed to identify immune related genes that were significantly associated with AA and MMR-deficient (MMR-d)/MSI-High (MSI-H) groups. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) assays for selected immune genes relative to two reference genes, (<i>C1ORF43</i> and <i>RAB7A</i>) were conducted on an independent set of AA (n = 59) vs. EA (n = 59) formalin-fixed paraffin embedded (FFPE) samples enriched for MMR-d/MSI-H samples. Multiple linear regression models were employed to investigate ancestry and MMR/MSI status while controlling other variables.</p><p><strong>Results: </strong>Multivariable regression analysis of the TCGA-COAD-READ data revealed that <i>CXCL10</i> expression was Lower in AA vs. EA groups and higher in MMR-d/MSI-H vs. MMR-proficient (MMR-p)/MSI-Low (MSI-L)+microsatellite stable (MSS) groups while controlling for COAD/READ location and stage. Neither COAD/READ stage or location were significant while controlling for ancestry and MMR/MSI status. CXCL10 is an important chemokine that regulates the tumor immune microenvironment. The number of AA MMR-d/MSI-H samples in the TCGA-COAD-READ dataset was too low (n = 9) to detect a significant effect of AA on <i>CXCL10</i> expression across MMR/MSI status. <i>CXCL10</i> mRNA levels measured by RT-qPCR in an independent set of COAD FFPE samples enriched for AA MMR-d/MSI-H samples, confirmed that <i>CXCL10</i> expression was higher in MMR-d/MSI-H samples compared to MMR-p/MSI-L+MSS, however, differences in <i>CXCL10</i> expression between AA vs. EA did not reach significance.</p><p><strong>Discussion: </strong>These results did not detect significant effects of AA on <i>CXCL10</i> expression across MMR/MSI status.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}