Journal of gastrointestinal oncology最新文献

{"title":"Increased expression of Ribonucleic acid export 1 (<i>RAE1</i>) gene promotes gastric carcinogenesis and is associated with Hippo signaling pathway.","authors":"Qianyu Zhu, Yanling Li, Qin Ouyang, Pingping He, Sisi Chen, Donghu Zhou, Yanmeng Li, Jie Xing, Huaduan Zi, Hengcheng Tang, Shuilong Guo, Jian Huang","doi":"10.21037/jgo-2025-1-1019","DOIUrl":"10.21037/jgo-2025-1-1019","url":null,"abstract":"<p><strong>Background: </strong>Ribonucleic acid export 1 (RAE1) autoantibody may have good potential for early detection of gastric cancer (GC). However, the carcinogenicity of RAE1 in GC remains unknown. We aimed to explore the role and the potential mechanism for RAE1 in the carcinogenesis of GC.</p><p><strong>Methods: </strong>Immunohistochemical assay was applied to analyze the expression of RAE1 in GC and precancerous lesion (PL) tissues and its relationship with clinical characteristics. The effects of RAE1 on proliferation, migration, apoptosis, and cell cycle were explored by constructing <i>RAE1</i> knockdown and overexpression in GC cells. The effects of <i>RAE1</i> knockdown on tumor growth were observed in a murine xenograft model. The signaling pathways involved in GC development that may be affected by RAE1 were investigated by transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.</p><p><strong>Results: </strong>Immunohistochemical expression of RAE1 was significantly higher in early GC patients than in PL and normal tissues, and the RAE1 expression was correlated with clinical stage (P<0.001). <i>In</i> <i>vitro,</i> knockdown of <i>RAE1</i> inhibited the proliferation and migration of GC cells with promoted apoptosis and arrested cell cycle in the S phase, while overexpression of <i>RAE1</i> showed the opposite trend. <i>In</i> <i>vivo</i>, knockdown of <i>RAE1</i> inhibited the growth of subcutaneous graft tumors in mice. Transcriptome sequencing and subsequent analysis of <i>RAE1</i> knockdown cells revealed that the Hippo signaling pathway was activated by <i>RAE1</i> knockdown.</p><p><strong>Conclusions: </strong>RAE1 promotes GC cells proliferation and migration and is associated with the inhibition of the Hippo signaling pathway, and may be a potential biomarker for early diagnosis and treatment of GC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"220"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproplasia-associated LOXL2 cooperates with <i>Helicobacter pylori</i> infection to promote gastric cancer progression via the FAK/Src signaling axis.","authors":"Jin Wang, Wenzi Meng, Jiahui Zhu, Guangzhao Tao, Yujian Xia, Yao Li, Xin Zhao, Yunliang Wang","doi":"10.21037/jgo-2026-0380","DOIUrl":"10.21037/jgo-2026-0380","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide, and <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is a well-established carcinogenic driver. Cuproplasia, a recently proposed copper-dependent biological state characterized by hyperplasia, metaplasia, and neoplasia, has emerged as a potential mechanistic link between metabolic reprogramming and tumor progression. However, the contribution of cuproplasia-related genes to <i>H. pylori</i>-associated gastric carcinogenesis remains poorly defined. This study aimed to identify cuproplasia-associated genes linked to <i>H. pylori</i>-positive GC and to clarify the functional role and underlying mechanism of LOXL2 in <i>H. pylori</i>-associated gastric cancer progression.</p><p><strong>Methods: </strong>Transcriptomic and clinical data were analyzed to construct a risk model for <i>H. pylori</i>-positive GC based on cuproplasia-related genes. Model performance was evaluated using receiver operating characteristic (ROC), nomogram, decision curve, and survival analyses. LOXL2 was subsequently selected for validation in clinical specimens by immunohistochemistry (IHC), western blotting, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional assays, including colony formation, wound healing, Transwell invasion, and mechanistic western blotting, were used to determine the biological effects of LOXL2 and <i>H. pylori</i> stimulation in GC cells.</p><p><strong>Results: </strong>A five-gene cuproplasia-related signature showed strong predictive performance for <i>H. pylori</i>-positive GC. Among the candidate genes, LOXL2 emerged as the most prominent biomarker. LOXL2 was significantly overexpressed in <i>H. pylori</i>-infected GC tissues and was associated with tumor size, differentiation status, ​tumor-node-metastasis (TNM) stage, lymph node metastasis, distant metastasis, and <i>H.</i> <i>pylori</i> positivity. <i>In vitro</i>, LOXL2 overexpression enhanced GC cell proliferation, migration, and invasion, whereas LOXL2 knockdown exerted the opposite effects. <i>H. pylori</i> stimulation further amplified the tumor-promoting effects of LOXL2. Mechanistically, LOXL2 and <i>H. pylori</i> cooperatively increased FAK and Src phosphorylation, upregulated Snail, and suppressed E-cadherin expression, thereby facilitating epithelial-mesenchymal transition (EMT).</p><p><strong>Conclusions: </strong>Rather than serving merely as a prognostic biomarker, LOXL2 functions as a cuproplasia-associated effector that cooperates with <i>H. pylori</i> infection to promote GC progression through activation of the FAK/Src signaling pathway, thereby providing new insights into the molecular mechanisms underlying <i>H.</i> <i>pylori</i>-associated gastric carcinogenesis.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"215"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Helicobacter pylori</i>-induced cystathionine-γ-lyase drives redox imbalance and metabolic remodeling in gastric cancer.","authors":"Yangyang Wang, Ruixue Xu, Ziqi Wang, Yufei Wu, Shuyi Han, Xi Zhang, Huanjie Li","doi":"10.21037/jgo-2026-0397","DOIUrl":"10.21037/jgo-2026-0397","url":null,"abstract":"<p><strong>Background: </strong><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is a major risk factor for gastric cancer (GC) and depends on nutrient and energy metabolism, particularly amino acids, for colonization. In host cells, cysteine is regulated by the transsulfuration (TSS) pathway, in which cystathionine-γ-lyase (CSE) generates cysteine, hydrogen sulfide (H₂S), and reactive sulfur species (RSS). Dysregulation of this pathway may contribute to gastric carcinogenesis. This study aims to investigate the role of CSE in <i>H. pylori</i>-associated GC and to characterize the associated alterations in sulfur metabolism and redox regulation.</p><p><strong>Methods: </strong>To model the gastric microenvironment during <i>H. pylori</i> infection and dissect the functional role of host CSE, we used <i>in vitro</i> infection models, CSE knockout mice, and metabolic profiling. The use of CSE knockout mice enables specific assessment of host CSE in gastric inflammation and tissue protection, providing a controlled and tractable <i>in vivo</i> system to study host metabolic enzyme function in the context of chronic bacterial infection, which has direct relevance to human gastric pathophysiology. Additionally, we examined the effects of garlic-derived organosulfur compounds, diallyl trisulfide (DATS) on <i>H. pylori</i> colonization, cysteine/TSS metabolism, oxidative stress, and GC cell proliferation.</p><p><strong>Results: </strong><i>H. pylori</i> infection upregulated CSE and altered cysteine metabolism, leading to RSS imbalance, pro-tumorigenic signaling, and inflammation. Systemic CSE deficiency <i>in vivo</i> exacerbated gastric inflammatory injury following <i>H. pylori</i> infection, indicating that CSE contributes to host tissue protection under inflammatory conditions. These observations suggest that CSE functions as a metabolic and redox regulator of which its biological impact depends on cellular context, facilitating tumor cell adaptation while preserving host homeostasis during infection.</p><p><strong>Conclusions: </strong>Our findings support a role for CSE in the metabolic and redox alterations associated with <i>H. pylori</i> infection and gastric carcinogenesis. The modulation of CSE-related pathways by DATS suggests that sulfur metabolism may represent a relevant area for future mechanistic and translational studies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"218"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological subtypes independently predict survival in ampullary carcinoma: a contemporary SEER nomogram study.","authors":"Minghui Zhang, Kuinan Tong, Chao Jing, Hongwei Wu, Xuemei Du, Kun Liu","doi":"10.21037/jgo-2026-0544","DOIUrl":"10.21037/jgo-2026-0544","url":null,"abstract":"<p><strong>Background: </strong>Ampullary adenocarcinoma (AAC) has distinct histopathological subtypes impacting prognosis, yet American Joint Committee on Cancer (AJCC) staging overlooks this distinction. Few large-scale studies have evaluated cancer-specific survival (CSS) or integrated subtypes into prognostic nomograms. This study aimed to evaluate the prognostic impact of histopathological subtypes on CSS in AAC patients and to develop a validated nomogram incorporating subtype for individualized risk stratification.</p><p><strong>Methods: </strong>Patients diagnosed between 2004-2021 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. CSS was compared using Kaplan-Meier and Cox models. A nomogram incorporating histopathological subtype was developed and validated using C-index, receiver operating characteristic (ROC) curves, and decision curve analysis.</p><p><strong>Results: </strong>Among 726 patients, 385 (53.0%) had intestinal type and 341 (47.0%) had pancreatobiliary/mixed type. Pancreatobiliary/mixed subtypes showed significantly worse CSS [median: 39 <i>vs</i>. 168 months; adjusted hazard ratio (HR) =1.60, 95% confidence interval (CI): 1.22-2.09, P<0.001] and higher proportions of T3 tumors (57.5% <i>vs</i>. 34.5%), nodal involvement (62.8% <i>vs</i>. 51.4%), and poor differentiation (35.8% <i>vs</i>. 19.2%; all P<0.01). The nomogram incorporating subtype, age, tumor (T)/node (N)/metastasis (M) stage, surgery, and chemotherapy achieved a C-index of 0.751 and areas under the curve (AUCs) of 0.812-0.837 for 1-, 3-, and 5-year CSS.</p><p><strong>Conclusions: </strong>Histopathological subtype independently predicts CSS in ampullary carcinoma. This subtype-inclusive nomogram outperforms conventional staging for individualized prediction, supporting precision oncology approaches.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"226"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artemisinin inhibits colorectal cancer progression via the FAM83A-AS1/HIF-1α axis.","authors":"Jinchuan Xi, Zhihan Li, Youqiang Liu, Zheng Li, Wenbo Niu, Lianmei Zhao, Bin Yu, Guiying Wang","doi":"10.21037/jgo-2026-0495","DOIUrl":"10.21037/jgo-2026-0495","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence indicates that the lncRNA <i>FAM83A-AS1</i> interacts closely with <i>HIF-1α</i> to modulate malignant biological behaviors and glycolytic metabolism in CRC. The mechanism underlying the effects of artemisinin on colorectal cancer (CRC) was investigated using a network pharmacology approach.</p><p><strong>Methods: </strong>The action network of artemisinin was analyzed using network pharmacology. Stable <i>FAM83A-AS1</i> and <i>HIF-1α</i> knockout cell models were established using a lentiviral system. The effects of artemisinin on cellular functions, including proliferation, metastasis, cell cycle progression, and glycolysis in CRC cells, were assessed through <i>in vitro</i> assays. The expression of <i>HIF-1α</i> was assessed by immunohistochemistry in tumor tissues from 219 patients with CRC, and its clinical associations were analyzed.</p><p><strong>Results: </strong>Artemisinin was predicted to target 96 proteins associated with CRC, including <i>HIF-1α</i>. Artemisinin inhibited proliferation, migration, and glycolysis, and induced cell cycle arrest in CRC cells. Artemisinin reduced the expression levels of Cyclin D1, <i>CDK4</i>, <i>HIF-1α</i>, <i>PKM2</i>, and N-cadherin. Artemisinin promoted proteasome-mediated degradation of HIF-1α protein. <i>HIF-1α</i> upregulated the expression of <i>FAM83A-AS1</i>, whereas knockdown of <i>FAM83A-AS1</i> reduced HIF-1α expression levels. The expression level of <i>HIF-1α</i> in tumor tissues was significantly higher than that in adjacent non-tumor tissues. <i>HIF-1α</i> expression was associated with tumor node metastasis (TNM) stage, tumor (T)​stage, node (N)​stage, carcinoembryonic antigen (CEA) levels, recurrence, metastasis, and prognosis in patients with CRC.</p><p><strong>Conclusions: </strong>Artemisinin promoted proteasome-mediated degradation of HIF-1α protein and inhibited CRC progression, potentially through the <i>FAM83A-AS1</i>/<i>HIF-1α</i> regulatory axis.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"228"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent FGFR pathway dependence: where does tinengotinib fit after FGFR inhibitor therapy in advanced cholangiocarcinoma?","authors":"Hideki Sasanuma, Hironori Yamaguchi","doi":"10.21037/jgo-2026-0668","DOIUrl":"10.21037/jgo-2026-0668","url":null,"abstract":"","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"274"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of prognostic nomograms for intrahepatic cholangiocarcinoma with concomitant hepatolithiasis after radical resection.","authors":"Jia Li, Xiao-Hui Wang, Yi Liu, Wei Chen, Xian-Hai Mao, Jia-Hua Yao, Hao Xie, He-Ping Kan","doi":"10.21037/jgo-2026-0541","DOIUrl":"10.21037/jgo-2026-0541","url":null,"abstract":"<p><strong>Background: </strong>Patients with intrahepatic cholangiocarcinoma (ICC) and concomitant hepatolithiasis constitute a distinct clinical subgroup, but prognostic models for this population are scarce. We therefore developed and validated nomograms to predict postoperative recurrence-free survival (RFS) and overall survival (OS).</p><p><strong>Methods: </strong>A total of 335 patients with ICC and concomitant hepatolithiasis who underwent radical resection were retrospectively enrolled. The cohort was randomly divided into a training cohort (n=161) and an internal validation cohort (n=69) from 230 patients, while 105 patients from an external institution constituted an independent validation cohort. Multivariable Cox regression analysis identified independent prognostic factors for RFS and OS. Nomograms based on these factors were subsequently constructed and validated using calibration curves, time-dependent receiver operating characteristic (ROC) curves, and C-index.</p><p><strong>Results: </strong>Vascular invasion, tumor number, lymph node metastasis, tumor size, carcinoembryonic antigen (CEA), microfibrillar-associated protein 4 (MFAP4), and albumin-bilirubin (ALBI) grade were independent predictors of RFS, while vascular invasion, tumor number, lymph node metastasis, carbohydrate antigen 19-9 (CA19-9), CEA, MFAP4, and ALBI grade were independently associated with OS. The resulting nomograms demonstrated good calibration and discrimination. In the training cohort, the C-index for RFS and OS were 0.840 and 0.852, respectively; these values were 0.823 and 0.832 in the internal validation cohort, and 0.862 and 0.870 in the external validation cohort.</p><p><strong>Conclusions: </strong>The developed nomograms accurately predicted postoperative RFS and OS in patients with ICC and concomitant hepatolithiasis, thereby supporting individualized risk stratification and postoperative management.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"248"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine tumors of unknown primary: a case report and review of tumors with gastroenteropancreatic features.","authors":"Kimiya Ghassemzadeh, Josephine E Chang, Reed I Ayabe, Oliver S Eng","doi":"10.21037/jgo-2026-0467","DOIUrl":"10.21037/jgo-2026-0467","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine tumors (NETs) are a complex group of tumors that arise from cells of the nervous and endocrine systems. They occur predominantly in the digestive or respiratory tracts, with those occurring along the gastrointestinal tract and pancreas classified as gastroenteropancreatic NETs. While certain features may suggest a gastroenteropancreatic origin, definitive localization of the primary site remains elusive in a substantial number of metastatic cases. These cases, referred to as NETs of unknown primary origin, can pose significant diagnostic, therapeutic, and prognostic implications. Here, we present a case of a NET of unknown primary, with features suggestive of gastroenteropancreatic origin, alongside a focused literature review highlighting key clinical features, diagnostic approaches, and therapeutic strategies to increase awareness of this challenging entity.</p><p><strong>Case description: </strong>A 19-year-old male with a history of celiac disease and gastroesophageal reflux disease (GERD) was found to have a grade 2 metastatic well-differentiated NET involving the perigastric region and the liver. On pre-operative workup, extensive imaging, and surgical exploration of the abdomen, no primary tumor was identified. The patient underwent cytoreductive surgery and was started on lanreotide injections with no definite evidence of disease recurrence or progression on imaging after a post-operative follow-up of 6 months. Ultimately, it remains unclear what the primary source of the neuroendocrine malignancy was in this patient despite endoscopic interventions, imaging modalities, and an array of histopathological tests.</p><p><strong>Conclusions: </strong>NETs of unknown primary, in particular those with gastroenteropancreatic features, remain poorly characterized in the literature, with no standardized diagnostic or management framework. In this case report, we present the case of a young male with metastatic NET of unknown primary, as well as highlight the features, mechanisms, workup, and management of such tumors. By presenting this case, we hope to emphasize the diagnostic complexity of these NETs with unknown primary and why careful consideration of undetectable lesions, atypical tumor origins, or spontaneous regression must be integrated into clinical decision-making and prognostic assessment.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"268"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of histological response by PET-CT after 2 weeks of neoadjuvant chemo-radiotherapy for rectal cancer: a prospective clinical trial.","authors":"Daniel Reinhorn, Yulia Kundel, Noa Gordon, Judit Prus, Sara Morgenstern, Nir Wasserberg, David Groshar, Hanna Bernstine, Baruch Brenner","doi":"10.21037/jgo-2026-1-0104","DOIUrl":"10.21037/jgo-2026-1-0104","url":null,"abstract":"<p><strong>Background: </strong>Early prediction of pathological response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) may help guide individualized treatment strategies. This prospective clinical trial aimed to evaluate whether interim ¹⁸F-fluorodeoxyglucose (¹⁸FDG)-positron emission tomography (PET)-computed tomography (CT) performed after 2 weeks of nCRT predicts histological response, including pathological complete response (pCR) and tumor regression grade (TRG).</p><p><strong>Methods: </strong>Twenty-one LARC patients receiving nCRT followed by surgery were included. ¹⁸FDG-PET-CT was performed at baseline and after 2 weeks of nCRT. Maximum and mean standardized uptake values (SUV-max and SUV-mean) and metabolic tumor volume (MTV) were calculated at both time points. pCR and TRG were assessed, and correlations between PET parameters and histological response were analyzed.</p><p><strong>Results: </strong>No significant differences in ΔSUV-mean%, ΔSUV-max%, and ΔMTV% were found between pCR and non-pCR groups or between TRG I-II and TRG III-V groups. Absolute SUV-mean and SUV-max values at baseline, and SUV-max and MTV values at 2 weeks, differed significantly between pCR and non-pCR groups. ROC analyses demonstrated discriminatory ability for predicting pCR, with area under the curve (AUC) values of 0.79-0.82.</p><p><strong>Conclusions: </strong>Early metabolic response after 2 weeks of nCRT did not correlate with pCR or TRG in LARC. Absolute SUV-mean and SUV-max values at baseline and absolute SUV-max and MTV values at 2 weeks showed predictive value for pCR.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"242"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MNAT1 in gastrointestinal cancers: mechanistic insights and therapeutic strategies-a narrative review.","authors":"Yanhua Zhang, Aiqi Hu, Chun Wen, Xi Yang, Xiaopai Wang, Sanping Zheng","doi":"10.21037/jgo-2026-1-0186","DOIUrl":"10.21037/jgo-2026-1-0186","url":null,"abstract":"<p><strong>Background and objective: </strong>Ménage à trois 1 (MNAT1) is an essential scaffolding subunit of the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex and has been increasingly implicated in cancer pathogenesis. Given the accumulating evidence linking MNAT1 to gastrointestinal (GI) malignancies, this narrative review aims to summarize current knowledge regarding the biological functions, oncogenic roles and therapeutic potential of MNAT1 in GI cancers.</p><p><strong>Methods: </strong>A literature search of the relevant databases (PubMed, Web of Science) was conducted, with a focus on recent and key publications in the English language. The search strategy included terms related to MNAT1, GI cancer, CAK complex and therapeutic targeting.</p><p><strong>Key content and findings: </strong>MNAT1 stabilizes the CAK complex and promotes cell-cycle progression by enabling CAK-mediated T-loop phosphorylation of cell-cycle CDKs. In addition, CAK functions as a module of the general transcription factor II H (TFIIH) and supports phosphorylation of RNA polymerase II (Pol II) at active promoters, sustaining oncogenic transcription programs. Therapeutic strategies that target MNAT1/CAK include CDK7 inhibition and CAK complex degradation, both of which can suppress transcriptional output and induce cell-cycle arrest. Combination regimens incorporating MNAT1/CAK targeting have also shown preclinical efficacy.</p><p><strong>Conclusions: </strong>This review summarizes current evidence on MNAT1 across multiple malignancies, with a focus on gastrointestinal cancers. We discuss MNAT1 as a potential biomarker for prognosis and treatment response and highlight opportunities and challenges for therapeutically targeting MNAT1/CAK in gastrointestinal cancer.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"264"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}