Journal of Gastroenterology最新文献

{"title":"Circulating miR-485-3p as a biomarker for VEGF-associated therapeutic response to atezolizumab plus bevacizumab in hepatocellular carcinoma.","authors":"Kyoko Oura, Asahiro Morishita, Rie Yano, Takushi Manabe, Kei Takuma, Mai Nakahara, Tomoko Tadokoro, Koji Fujita, Shima Mimura, Joji Tani, Miwa Tatsuta, Takashi Himoto, Tsutomu Masaki, Hideki Kobara","doi":"10.1007/s00535-025-02239-7","DOIUrl":"10.1007/s00535-025-02239-7","url":null,"abstract":"<p><strong>Background: </strong>In atezolizumab/bevacizumab (atezo/bev) therapy for unresectable hepatocellular carcinoma (HCC), the tumor immune environment is regulated through vascular endothelial growth factor A (VEGFA) inhibition to maximize immune checkpoint blockade; however, evidence for VEGFA as a biomarker is limited. This study aimed to investigate serum VEGFA and associated microRNAs (miRNAs) as rapid biomarkers and their regulatory mechanisms in the microenvironment of HCC.</p><p><strong>Methods: </strong>Fifty-four patients with unresectable HCC who were treated with atezo/bev therapy were enrolled and assigned into objective response (OR) and non-OR groups according to the best therapeutic response in 12 weeks using the modified response evaluation criteria in solid tumors. Serum VEGFA levels and associated miRNA expression were compared. Furthermore, the effect of cell transfection with specific miRNA was investigated.</p><p><strong>Result: </strong>There was no significant difference in the pre-treatment serum VEGFA levels between the groups; however, the 3-week/pre-treatment ratio of serum VEGFA levels was significantly lower in the OR group than in the non-OR group. The pre-treatment serum levels of 10 miRNAs, especially miR-485-3p involved in VEGFA expression, were higher in the OR group than in the non-OR group and were further elevated after 1-7 days and 3 weeks. MiR-485-3p suppressed HuH-7 migration, enhanced the expression of protein inhibitor of activated (PIA) signal transducer and activator of transcription 3 (STAT3) (PIAS3), and suppressed the expression of phosphorylated STAT3/VEGFA.</p><p><strong>Conclusion: </strong>Circulating miR-485-3p is a more sensitive biomarker than VEGFA for the early prediction of therapeutic response in atezo/bev therapy for HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"770-782"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive prediction of the clinical benefit of immunotherapy in hepatocellular carcinoma.","authors":"Atsushi Ono, C Nelson Hayes, Ryoichi Miura, Tomokazu Kawaoka, Masataka Tsuge, Shiro Oka","doi":"10.1007/s00535-025-02251-x","DOIUrl":"https://doi.org/10.1007/s00535-025-02251-x","url":null,"abstract":"<p><p>Long-term survival following a diagnosis of hepatocellular carcinoma (HCC) is greatly diminished when transplantation and surgical resection are ruled out. Fortunately, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced unresectable HCC (uHCC), prolonging median survival by over a year. T lymphocytes normally eliminate neoplastic cells, but some tumors suppress this response by binding to immune checkpoint receptors. Blocking this interaction via ICIs restores immune-mediated targeting of cancer cells. While ICI-based combination immunotherapy is currently recommended as the first-line systemic therapy for uHCC, the objective radiological response rate remains limited to 20-30%, as not all tumors exploit this mechanism. Consequently, strategies are being explored to modulate the immune microenvironment into a \"hot\" environment more responsive to ICIs by combining local therapies such as transarterial chemoembolization, ablation, and radiation therapy. Therapeutic options have also expanded beyond ICIs, emphasizing the importance of selecting the most appropriate treatment. Therefore, the development of biomarkers capable of predicting the efficacy of immunotherapy is a priority. Direct evaluation of immune cell infiltration through biopsy is currently the most effective method but involves issues such as invasiveness and susceptibility to sampling bias. In this review, we aim to highlight promising non-invasive biomarkers and scoring systems that have the potential to improve treatment outcomes, including blood-based biomarkers such as lymphocyte ratios, cytokines, C-reactive protein, and alpha-fetoprotein; imaging biomarkers such as MRI, ultrasound, and contrast-enhanced CT; and other clinical indicators such as sarcopenia, grip strength, and diversity of the gut microbiome.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular imaging of gastrointestinal stromal tumor using anti-c-KIT antibody and its fragments.","authors":"Takanori Kashihara, Yutaka Kawano, Shota Fujimoto, Tatsuya Segawa, Mamoru Shimizu, Takanori Miyake, Koichi Okamoto, Naoki Muguruma, Yasushi Sato, Tetsuji Takayama","doi":"10.1007/s00535-025-02264-6","DOIUrl":"https://doi.org/10.1007/s00535-025-02264-6","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal stromal tumors (GISTs) are malignant subepithelial tumors, known for their poor prognosis due to distant metastasis. Because GIST is covered by a normal mucosal layer, effective tissue biopsy under conventional endoscopy is difficult, thereby leading to delayed diagnosis and a dismal prognosis. We performed molecular imaging of GIST targeting c-KIT using fluorescence-labeled anti-c-KIT antibody/fragments and fluorescent endoscopy.</p><p><strong>Methods: </strong>Mouse anti-human c-KIT monoclonal antibody, its F(ab')₂ and Fab fragments were labeled with AF680. Two GIST cell lines (GIST-T1, GIST-882M) were used for experiments. Antibodies were intravenously administered to mice xenografted with GIST-T1 or GIST-882M, and each tumor was observed using IVIS Spectrum and self-developed simple fluorescent endoscopy.</p><p><strong>Results: </strong>The GIST-T1 cell live imaging revealed strong signals on cell membranes after 1 min incubation, and thereafter, they aggregated and internalized inside the cells within 130 min in all antibody/fragment groups. In vivo mouse experiments, AF680-labeled IgG slowly accumulated in tumors peaking at 24 h after injection. However, AF680-labeled F(ab')₂ and Fab rapidly accumulated in tumors peaking at 1-2 h, and completely cleared from the body within 24 h. Fab showed the strongest fluorescence intensity in tumors. Fluorescence endoscopy could clearly detect GIST xenograft tumors 1-2 h after AF680-labeled F(ab')₂ and Fab injection.</p><p><strong>Conclusions: </strong>AF680-labeled antibody/fragments showed clear and specific fluorescence signals in GIST xenografts in mice. Particularly, AF680-labeled Fab showed the strongest signal intensity at 1-2 h post-administration and rapid clearance, suggestive of the safety. This approach may enable molecular imaging diagnosis of GIST by endoscopy in outpatient settings in the future.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of neuropilin-1 and hepatocyte growth factor/C-Met pathway in liver fibrosis progression in hepatocyte-specific NRP-1 knockout mice.","authors":"Han Ding, Huanran Lv, Minghao Sui, Xinyu Wang, Yanning Sun, Miaomiao Tian, Shujun Ma, Yuchan Xue, Miao Zhang, Xin Wang, Jianni Qi, Le Wang, Qiang Zhu","doi":"10.1007/s00535-025-02262-8","DOIUrl":"https://doi.org/10.1007/s00535-025-02262-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocyte growth factor (HGF)/c-Met signaling critically influences liver fibrosis, but its interaction with neuropilin-1 (NRP-1) in hepatocytes remains unclear. We investigated the role of hepatocyte-specific NRP-1 deletion in liver fibrosis progression and its relationship with the HGF/c-Met pathway.</p><p><strong>Methods: </strong>Hepatocyte-specific NRP-1 knockout mice were generated using the Cre-lox system, and liver fibrosis was induced by carbon tetrachloride injections or a methionine- and choline-deficient diet. Fibrosis severity, hepatocyte injury, and cytokine secretion were evaluated via histology, biochemical assays, and molecular analyses in isolated hepatocytes. In vitro experiments were conducted in primary hepatocytes and Huh7 cells using lentiviral overexpression and knockdown of NRP-1. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to analyze transcription factor binding to the NRP-1 promoter.</p><p><strong>Results: </strong>Hepatocyte NRP-1 expression increased significantly during liver fibrosis and was positively correlated with HGF/c-Met expression and fibrosis severity. In vivo, NRP-1 inhibition reduced extracellular matrix accumulation and abnormal angiogenesis in Alb-Cre NRP-1^f/f mice. In vitro, NRP-1 blockade inhibited c-Met activation and reduced transforming growth factor-beta and vascular endothelial growth factor secretion in hepatocytes. NRP-1 functioned as a co-receptor for HGF/c-Met, with HGF upregulating NRP-1 expression at transcript and protein levels. NRP-1 promoted fibrosis through the Met/extracellular signal-regulated kinase pathway. Furthermore, HGF increased retinoic acid receptor alpha expression, promoting NRP-1 transcription.</p><p><strong>Conclusions: </strong>HGF-induced upregulation of hepatocyte NRP-1, mediated by RARA binding to its promoter, drives liver fibrosis through c-Met pathway activation, highlighting NRP-1 as a potential therapeutic target for liver fibrosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEC61G promotes colorectal cancer progression by regulating cytosolic Ca²⁺ concentration.","authors":"Satoshi Higuchi, Hajime Otsu, Takaaki Masuda, Masahiro Hashimoto, Yusuke Nakano, Kiyotaka Hosoda, Kosuke Hirose, Tomohiko Ikehara, Takashi Ofuchi, Yasuo Tsuda, Yusuke Yonemura, Mamoru Uemura, Hidetoshi Eguchi, Yuichiro Doki, Koshi Mimori","doi":"10.1007/s00535-025-02259-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02259-3","url":null,"abstract":"<p><strong>Background: </strong>Intracellular calcium (Ca²⁺) signaling regulates key cancer processes. Research findings suggest that the SEC61 complex, involved in protein translocation, contributes to calcium leakage from the endoplasmic reticulum. However, the mechanism by which SEC61 Translocon Subunit Gamma (SEC61G), a component of this complex, influences colorectal cancer (CRC) progression remains unclear.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed using The Cancer Genome Atlas data sets to identify candidate genes on chromosome 7p, examine their association with DNA copy number amplification. In addition, SEC61G expression in CRC cells and tissues was validated using reverse-transcription quantitative polymerase chain reaction and immunohistochemistry. Moreover, in vitro and in vivo experiments were performed to investigate the effects of SEC61G overexpression and knockdown on CRC cell proliferation. Furthermore, publicly available single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) data were used to validate the role of SEC61G in CRC.</p><p><strong>Results: </strong>SEC61G was significantly upregulated in CRC tissues and was correlated with poor prognosis in patients with CRC. SEC61G overexpression enhanced cell proliferation and activated the EGFR pathway, promoting cell cycle progression from the G1 to S phase. In addition, SEC61G overexpression increased cytosolic Ca²⁺ levels, which activated EGFR signaling via calmodulin. Moreover, analyses of scRNA-seq and ST-seq data confirmed that SEC61G expression was higher in tumor epithelial cells and that it was co-expressed with EGFR pathway-related genes.</p><p><strong>Conclusions: </strong>SEC61G promotes CRC progression by regulating cytosolic Ca²⁺ concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis.","authors":"Motoi Sawahashi, Yoichi Kakuta, Takeo Naito, Soshi Okazaki, Kinuko Ohneda, Masatsugu Orui, Taku Obara, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Fuji Nagami, Atsushi Hozawa, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Tsuyoshi Shirai, Hiroshi Fujii, Atsushi Masamune","doi":"10.1007/s00535-025-02263-7","DOIUrl":"https://doi.org/10.1007/s00535-025-02263-7","url":null,"abstract":"<p><strong>Background: </strong>A method for predicting ulcerative colitis (UC) onset has not been established. Serum autoantibodies have been suggested as potential predictive biomarkers for UC onset. We aimed to validate the risks associated with serological and environmental factors and construct a model for predicting UC development.</p><p><strong>Methods: </strong>Using the population-based cohort studies (n > 83,000), we identified 42 individuals who were diagnosed with UC later in life and compared them with matched healthy controls. We analyzed serum anti-integrin αvβ6 antibody (anti-αvβ6) and anti-endothelial protein C receptor antibody (anti-EPCR) titers, and lifestyle and dietary habits to explore UC onset predictors. The predictive performance of the models was evaluated based on these predictors.</p><p><strong>Results: </strong>The sensitivity and specificity of anti-EPCR for predicting UC onset were 51.4% and 97.8%, respectively, comparable to those of anti-αvβ6 (52.5% and 97.6%, respectively). The proportion of individuals with insomnia was significantly higher in the preclinical UC group (adjusted odds ratio = 2.14, 95% confidence interval [CI] 1.11-4.04, p = 0.019). The predictive performance of anti-EPCR alone was high with an area under the curve (AUC) of 0.89 (95%CI 0.83-0.96), and that of anti-EPCR combined with anti-αvβ6 was even better with an AUC of 0.92 (95%CI 0.87-0.97); the lifestyle model had lower predictive accuracy (AUC = 0.65, 95%CI 0.55-0.74).</p><p><strong>Conclusions: </strong>Anti-EPCR and anti-αvβ6 each strongly predict UC onset. The combined anti-EPCR and anti-αvβ6 model had stronger predictive performance than the single models.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External validation of the eCura system and comparison with the W-eCura score for predicting lymph node metastasis after non-curative endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective cohort study.","authors":"Yohei Yabuuchi, Yuichi Masui, Ken Kumagai, Hiroyoshi Iwagami, Katsuyuki Murai, Takeshi Setoyama, Tomomasa Tochio, Takahiro Utsumi, Takaaki Yoshikawa, Osamu Araki, Shintaro Murakami, Motoya Kitami, Kenshi Matsuura, Naoki Kanda, Eriko Hishitani, Junya Tanaka, Saiko Marui, Kozo Ikuta, Hiroyuki Yoshida, Yoshitaka Nishikawa, Yuki Nakanishi, Hiroshi Seno","doi":"10.1007/s00535-025-02261-9","DOIUrl":"https://doi.org/10.1007/s00535-025-02261-9","url":null,"abstract":"<p><strong>Background: </strong>The eCura system is a widely used risk-scoring model for predicting lymph node metastasis (LNM) after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), but its external validation is limited. Recently, the W-eCura score, a modified version, was proposed. We aimed to validate the eCura system and compare its discriminatory performance with the W-eCura score.</p><p><strong>Methods: </strong>A multicenter retrospective study was conducted using data from 19 Japanese institutions. The patients who underwent ESD for EGC followed by gastrectomy with lymph node dissection were included. The predictive performance of the eCura system, including calibration and discrimination, was evaluated and its discrimination was compared with the W-eCura score.</p><p><strong>Results: </strong>Among 901 eligible patients, 65 cases (7.2%) showed LNM. The eCura system demonstrated good calibration, with a calibration-in-the-large of -0.008 (95% confidence interval [CI] -0.024-0.010), an observed-to-expected ratio of 0.905 (95% CI 0.707-1.121), and a calibration slope of 0.975 (95% CI 0.692-1.257). Discrimination was also good, with a C-statistic of 0.741 (95% CI 0.676-0.806). In patients evaluable for both systems, the C-statistics for the eCura system and W-eCura score were 0.745 (95% CI 0.675-0.816) and 0.750 (95% CI 0.684-0.817), respectively, showing no significant difference (P = 0.547).</p><p><strong>Conclusions: </strong>The eCura system was validated as a reliable tool for predicting LNM following ESD in real-world clinical settings.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between excessive supragastric belching and esophageal reflux factors in patients with PPI-refractory GERD in Japan.","authors":"Yukihiro Shuto, Masahiro Saito, Tomoyuki Koike, Kaoru Koizumi, Yumiko Kaise, Kazuma Yachi, Yutaka Hatayama, Yohei Ogata, Xiaoyi Jin, Takeshi Kanno, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune","doi":"10.1007/s00535-025-02258-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02258-4","url":null,"abstract":"<p><strong>Background: </strong>No studies have evaluated the prevalence of supragastric belching (SGB) in Japanese patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD) under off-PPI conditions. This study aimed to clarify the association between excessive SGB and esophageal reflux factors.</p><p><strong>Methods: </strong>Seventy-nine patients with PPI-refractory NERD under off-PPI treatment were evaluated using 24-h multichannel intraluminal impedance pH monitoring and high-resolution impedance manometry.</p><p><strong>Results: </strong>The prevalence values of excessive SGB overall and in the true NERD, reflux hypersensitivity, and function heartburn subtypes were 19.0%, 35.7%, 5.3%, and 12.5%, respectively. The monitoring results demonstrated that, compared with those without excessive SGB, patients with excessive SGB had a significantly higher total number of reflux events (63 episodes vs. 39 episodes, p = 0.01) and significantly greater acid exposure time (6.1% vs. 1.35%, p = 0.01). However, bolus exposure did not differ significantly between the groups (p = 0.09). The manometry findings showed no significant differences in lower esophageal sphincter pressure, integrated relaxation pressure, and distal contractile integral between the groups. Regarding gastroesophageal reflux, 22% of the SGB episodes were preceded by reflux, 55% occurred independently, and 23% were followed by reflux.</p><p><strong>Conclusions: </strong>The prevalence of excessive SGB in Japanese patients with PPI-refractory NERD under off-PPI conditions was 19.0% and most commonly observed in patients with true NERD (35.7%). Patients with excessive SGB exhibited increased esophageal acid exposure, and reflux events were sometimes observed before SGB episodes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer.","authors":"Satoshi Nishiwada, Kota Nakamura, Naoki Ozu, Taichi Terai, Yuichiro Kohara, Minako Nagai, Takeshi Sakata, Shunsuke Doi, Yasuko Matsuo, Satoshi Yasuda, Toshihiro Tanaka, Masayuki Sho","doi":"10.1007/s00535-025-02260-w","DOIUrl":"https://doi.org/10.1007/s00535-025-02260-w","url":null,"abstract":"<p><strong>Background: </strong>Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC.</p><p><strong>Methods: </strong>To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53].</p><p><strong>Results: </strong>The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86).</p><p><strong>Conclusions: </strong>We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormalities of intracellular organelles in metabolic dysfunction-associated steatotic disease.","authors":"Hidenori Kido, Eishiro Mizukoshi, Masahiro Yanagi, Li Shihui, Takuya Seike, Hidetoshi Nakagawa, Tetsumori Yamashima, Yoshitake Shiraishi, Noriyuki Ozaki, Kenichi Harada, Hikari Okada, Hisanori Goto, Kumi Kimura, Yasuhiko Yamamoto, Taro Yamashita","doi":"10.1007/s00535-025-02257-5","DOIUrl":"https://doi.org/10.1007/s00535-025-02257-5","url":null,"abstract":"<p><strong>Background: </strong>The concept of metabolic dysfunction-associated steatotic disease (MASLD) is increasingly being recognized. The mechanisms contributing to hepatocellular injury include oxidative stress owing to mitochondrial dysfunction, endoplasmic reticulum (ER) stress owing to abnormal protein accumulation in the rough ER, and disruption of cellular homeostasis and metabolic regulation to autophagic dysfunction. However, the morphological abnormalities of these intracellular organelles remain unclear.</p><p><strong>Methods: </strong>Liver tissues from model mice of MASLD, patients with MASLD, and respective controls were subjected to histopathological examination using light microscopy, and intracellular organelles were analyzed via transmission electron microscopy (TEM).</p><p><strong>Results: </strong>In model mice of MASLD, the progression of MASLD pathology was associated with abnormalities in mitochondria, glycogen granules, and rough ER. Based on these findings, the electron microscopic observations of these intracellular organelles were classified, weighted, and evaluated in liver tissues of patients with MASLD. The electron microscopic findings were significantly relatively frequent in patients with MASLD and correlated with existing histopathological scoring.</p><p><strong>Conclusions: </strong>Using TEM, we identified characteristic abnormalities in intracellular organelles specific to MASLD. These findings contribute to the understanding of the mechanisms underlying hepatocellular injury in MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}