Journal of Gastroenterology最新文献

{"title":"Low HDL cholesterol levels in women and hypertriglyceridemia in men: predictors of MASLD onset in individuals without steatosis.","authors":"Tsubasa Tsutsumi, Takumi Kawaguchi, Hideki Fujii, Yoshihiro Kamada, Yuichiro Suzuki, Koji Sawada, Miwa Tatsuta, Tatsuji Maeshiro, Hiroshi Tobita, Takemi Akahane, Chitomi Hasebe, Miwa Kawanaka, Takaomi Kessoku, Yuichiro Eguchi, Hayashi Syokita, Atsushi Nakajima, Tomoari Kamada, Hitoshi Yoshiji, Hiroshi Sakugawa, Asahiro Morishita, Tsutomu Masaki, Takumi Ohmura, Toshio Watanabe, Yoshioki Yoda, Nobuyuki Enomoto, Masafumi Ono, Kanako Fuyama, Kazufumi Okada, Naoki Nishimoto, Yoichi M Ito, Hirokazu Takahashi, Michael R Charlton, Mary E Rinella, Yoshio Sumida","doi":"10.1007/s00535-025-02242-y","DOIUrl":"10.1007/s00535-025-02242-y","url":null,"abstract":"<p><strong>Background: </strong>Individuals with metabolic-associated steatotic liver disease (MASLD) have a worse prognosis compared to patients without steatosis, and its prevalence is increasing. However, detailed risk factors based on obesity and sex remain unclear. We aimed to investigate the impact of cardiometabolic risk factors (CMRFs) on the risk of MASLD in individuals without pre-existing SLD.</p><p><strong>Methods: </strong>SLD was diagnosed by ultrasonography. Non-SLD individuals were followed 65,657 person-years. Incidence rates of MASLD were assessed by Kaplan-Meier analysis. Furthermore, independent factors associated with the development of MASLD were identified using Cox regression analysis, stratified by four groups: obese men, non-obese men, obese women, and non-obese women.</p><p><strong>Results: </strong>The overall incidence rate of MASLD was 39.3/1,000 person-years. The cumulative incidence was highest in obese men, followed by obese women, non-obese men, and non-obese women. Two or more CMRFs increased the risk of MASLD in all groups. Low HDL cholesterol level was the strongest independent risk factor in both obese and non-obese women and hypertriglyceridemia for both obese and non-obese men. The impact of these CMRFs was stronger in non-obese individuals. (HR [95% CI]: women non-obese 1.9 [1.5-2.4], obese 1.4 [1.1-1.8]; men non-obese 2.3 [1.9-2.9], obese 1.5 [1.2-2.0]).</p><p><strong>Conclusions: </strong>Multiple CMRFs are important to MASLD development, regardless of sex and obesity. In this Japanese cohort, low HDL cholesterol in women and hypertriglyceridemia in men were the most significant risk factors, especially among the non-obese group. These findings suggest that sex-specific CMRFs may play a role in the development of MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"891-904"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649169","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":"Myeloid-derived MANF ameliorates ethanol-induced liver injury by enhancing microRNA-223 expression.","authors":"Huiyuan Xie, Pingping Zhang, Shanru Yang, Jia Du, Yan Ren, Xianxian Gao, Na Li, Tao Yang, Yang Ma, Xin Hou","doi":"10.1007/s00535-025-02240-0","DOIUrl":"10.1007/s00535-025-02240-0","url":null,"abstract":"<p><strong>Background: </strong>Myeloid cells play a pivotal role in the pathogenesis of alcoholic liver disease (ALD), yet the mechanisms regulating their function and specific contributions to ALD remain inadequately understood. This study aims to investigate the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in the development of ALD.</p><p><strong>Methods: </strong>Myeloid-specific Manf knockout mice and wild-type controls were fed an ethanol-based diet for 10 days, followed by a single ethanol binge. Hepatic MANF levels, along with the correlation between MANF and inflammatory factors in patients with alcoholic hepatitis, were analyzed using the GSE28619 dataset.</p><p><strong>Results: </strong>Our study demonstrated that myeloid MANF expression in the liver was upregulated following chronic-plus-binge ethanol exposure. Deletion of the Manf gene in myeloid cells, including neutrophils, exacerbated ethanol-induced liver injury, steatosis, neutrophil infiltration, and reactive oxygen species production. Mechanistic analysis revealed that MANF promotes neutrophil miR-223 expression, a key anti-inflammatory factor in these cells. MANF enhances miR-223 transcription by increasing the expression of the transcription factor PU.1 via p38 mitogen-activated protein kinase signaling. In addition, hepatic MANF levels were elevated in patients with alcoholic hepatitis and correlated with IL-6, IL-1β, and phagocytic oxidase (phox) p47^phoxlevels.</p><p><strong>Conclusion: </strong>Myeloid-derived MANF mitigates alcohol-induced liver injury by upregulating the neutrophilic p38-PU.1-miR-223 axis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"877-890"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669980","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":"Posttreatment serum CXCL10 level stratifies survival in compensated and decompensated cirrhotic patients due to chronic hepatitis C virus infection after direct-acting antiviral therapy.","authors":"Takanori Suzuki, Kentaro Matsuura, Yuki Tahata, Hayato Hikita, Ryotaro Sakamori, Norifumi Kawada, Nobuyuki Enomoto, Daiki Miki, Hiroshi Yatsuhashi, Hidekatsu Kuroda, Taro Yamashita, Hitoshi Yoshiji, Masayuki Kurosaki, Seiichi Mawatari, Hisamitsu Miyaaki, Yasuhiro Asahina, Yoichi Hiasa, Satoshi Mochida, Yasunari Nakamoto, Taro Takami, Takahiro Kodama, Tomohide Tatsumi, Tetsuo Takehara","doi":"10.1007/s00535-025-02282-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02282-4","url":null,"abstract":"<p><strong>Aim: </strong>We investigated the usefulness of serum CXCL10 levels for predicting prognosis in hepatitis C virus (HCV)-infected patients with compensated and decompensated cirrhosis (cLC and dLC) after direct-acting antiviral (DAA) therapy.</p><p><strong>Methods: </strong>This nationwide multicenter study enrolled 212 HCV-associated LC patients, consisting of 113 cLC and 99 dLC patients, receiving DAA therapy, who had preserved serum samples. Serum CXCL10 levels were measured at pretreatment (pre-CXCL10) and posttreatment (12 or 24 weeks after the end of treatment: EOT12W or EOT24W) (post-CXCL10). We evaluated the relationship between these levels and liver transplantation (LT)-free overall survival (OS) and clinical outcomes.</p><p><strong>Results: </strong>During the observational period (median: 37 months), 27 patients developed dLC events and 20 died. The post-CXCL10 levels were significantly higher in dLC than in cLC (P = 0.006) and among patients who died than those who survived (P < 0.001). The cutoff value of serum post-CXCL10 level for discriminating the occurrence of death (345 pg/mL) could predict LT-free OS in groups of all, cLC, and dLC patients (P < 0.001, P = 0.007, and P < 0.001, respectively). Multivariate analysis on factors associated with LT-free OS demonstrated that age (HR 1.076; P = 0.013), Child-Pugh score at EOT12W (HR 1.575; P = 0.009), and serum post-CXCL10 level (HR 1.003; P = 0.001) were independent factors.</p><p><strong>Conclusions: </strong>The serum post-CXCL10 level was independently related to survival in HCV-associated LC patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540501","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":"Impact of early aggressive treatment on long-term biochemical marker patterns in inflammatory bowel disease.","authors":"Yu Kyung Jun, Yonghoon Choi, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee, Soyeon Ahn, Hyuk Yoon","doi":"10.1007/s00535-025-02244-w","DOIUrl":"10.1007/s00535-025-02244-w","url":null,"abstract":"<p><strong>Backgrounds: </strong>The disease course of inflammatory bowel disease (IBD) is highly variable; early and precise identification of patients with poor outcomes is crucial. We aimed to classify the long-term disease course of IBD using biochemical markers and evaluate the clinical factors associated with different disease courses.</p><p><strong>Methods: </strong>A latent class mixed model was employed to identify distinct trajectories of C-reactive protein (CRP) and fecal calprotectin (FCP) levels in 256 and 635 patients with Crohn's disease (CD) and ulcerative colitis (UC), respectively, from a tertiary hospital cohort. Multinomial logistic regression was used to evaluate the relationships between various trajectories and clinical variables.</p><p><strong>Results: </strong>Three trajectories were identified for CD and UC: class 1, early and sustained biochemical remission; class 2, delayed remission; and class 3, prolonged difficulty in achieving remission for > 5 years. For patients with CD, early immunomodulator initiation was associated with a high likelihood of belonging to class 1 in the CRP trajectory analysis, whereas early advanced therapy increased the probability of belonging to class 1 in the FCP trajectory analysis. CRP trajectory analysis showed no significant associations in patients with UC. Younger age at diagnosis and early immunomodulator initiation were associated with higher odds of being in class 2 or 3, whereas current smoking was associated with a high likelihood of being in class 1 in the FCP trajectory analysis.</p><p><strong>Conclusions: </strong>Early aggressive medical treatment for CD may lead to long-term biochemical remission, whereas no similar association was observed in UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"854-865"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age distribution and risk factors for Barrett's esophagus by sex at health check-up settings in Japan.","authors":"Sho Fukuda, Kenta Watanabe, Dai Kubota, Nobutake Yamamichi, Yu Takahashi, Yoshitaka Watanabe, Kyoichi Adachi, Norihisa Ishimura, Tomoyuki Koike, Hideyuki Sugawara, Kiyotaka Asanuma, Yasuhiko Abe, Takashi Kon, Eikichi Ihara, Kazuhiro Haraguchi, Yoshihiro Otsuka, Rie Yoshimura, Yugo Iwaya, Takuma Okamura, Noriaki Manabe, Akira Horiuchi, Mio Matsumoto, Kengo Onochi, So Takahashi, Tatsuki Yoshida, Yosuke Shimodaira, Katsunori Iijima","doi":"10.1007/s00535-025-02222-2","DOIUrl":"10.1007/s00535-025-02222-2","url":null,"abstract":"<p><strong>Background: </strong>Given the high prevalence of esophageal adenocarcinoma and Barrett's esophagus (BE), a precancerous lesion, among males, it is important to understand the characteristics of BE by sex to develop an effective endoscopic surveillance program in Japan. The present study examined the age distribution and risk factors for BE in the Japanese health check-up cohort by sex.</p><p><strong>Methods: </strong>The data set at baseline of our preceding multicenter study, comprising a total of 33,478 individuals who underwent upper endoscopic screening at 17 health check-up institutes across Japan, was utilized. BE and long-segment BE (LSBE) were defined as a columnar-lined esophagus ≥ 1 cm and ≥ 3 cm, respectively. Logistic regression analyses were performed to ascertain the factors associated with BE.</p><p><strong>Results: </strong>BE was relatively common (10-20%) across all 10-year age groups in men and women. Although the prevalence of LSBE was rare (0.2%), it began to increase at younger ages in men. In the multivariable analysis of the male cohort, while body mass index (BMI) was negatively associated with BE with an adjusted odds ratio (95% confidence interval) of 0.84 (0.74-0.95), waist circumference (WC) was positively associated with 1.26 (1.13-1.41). Furthermore, this association was more pronounced in LSBE. In contrast, no such association was observed between BMI or WC and BE in women.</p><p><strong>Conclusion: </strong>The nationwide Japanese multicenter study yielded insights into the age distribution of BE in the Japanese population. Furthermore, our findings indicate that a low BMI/high WC represents a significant risk factor for BE in the Japanese male population.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"820-828"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion.","authors":"Ryota Mori, Takayuki Ogino, Mari Murakami, Hisako Kayama, Daisuke Okuzaki, Atsuyo Ikeda, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Hidekazu Takahashi, Norikatsu Miyoshi, Mamoru Uemura, Hiroki Ikeuchi, Kiyoshi Takeda, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi","doi":"10.1007/s00535-025-02243-x","DOIUrl":"10.1007/s00535-025-02243-x","url":null,"abstract":"<p><strong>Background: </strong>Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance.</p><p><strong>Methods: </strong>Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study.</p><p><strong>Results: </strong>Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-γ expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-γ-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (≥ 80%) had shorter relapse-free survival (P = 0.03).</p><p><strong>Conclusions: </strong>Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-γ secretion, affecting post-surgery intestinal outcomes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"838-853"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current management and future perspectives of covert hepatic encephalopathy in Japan: a nationwide survey.","authors":"Takao Miwa, Mio Tsuruoka, Hajime Ueda, Tamami Abe, Hiroki Inada, Yoshimi Yukawa-Muto, Masatsugu Ohara, Taeang Arai, Yasuyuki Tamai, Hiroshi Isoda, Tomoko Tadokoro, Tatsunori Hanai, Takanori Ito, Nobuharu Tamaki, Akira Sakamaki, Yoshihiko Aoki, Fujimasa Tada, Sachiyo Yoshio, Hirokazu Takahashi, Asahiro Morishita, Tsuyoshi Ishikawa, Jun Inoue, Goki Suda, Chikara Ogawa, Masanori Atsukawa, Atsushi Hiraoka, Hidekatsu Kuroda, Tadashi Namisaki, Takashi Honda, Takumi Kawaguchi, Yasuhito Tanaka, Shuji Terai, Tadashi Ikegami, Hitoshi Yoshiji, Motoh Iwasa, Masahito Shimizu","doi":"10.1007/s00535-025-02232-0","DOIUrl":"10.1007/s00535-025-02232-0","url":null,"abstract":"<p><strong>Background: </strong>Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan.</p><p><strong>Methods: </strong>A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated.</p><p><strong>Results: </strong>Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams.</p><p><strong>Conclusions: </strong>Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"866-876"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of targeted α-emitter therapy in gastroenteropancreatic neuroendocrine neoplasms.","authors":"Naoyuki Yamaguchi, Jing-Jing Wei, Hajime Isomoto","doi":"10.1007/s00535-025-02241-z","DOIUrl":"10.1007/s00535-025-02241-z","url":null,"abstract":"<p><p>Effective therapeutic strategies for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remain challenging, including a lack of response to therapy and post-treatment relapse. The rapid development of targeted radionuclide therapy (TRT) offers promising data for patients with somatostatin receptor (SSTR)-expressing tumors. This approach exhibits more advantages than somatostatin analog (SSA) therapy, which is primarily effective for well-differentiated and slow-growing GEP-NENs. Fortunately, some clinical studies on peptide receptor radionuclide therapy (PRRT) labeled with α-emitting radionuclides for GEP-NENs patients showed effective results for those with more advanced GEP-NENs, or those with malignant metastasis. For the improvement of clinical efficacy and the decline in the incidence of treatment-related relapse, recent progress in developing novel techniques and effective disease management strategies for optimal targeting has led to the emergence of targeted alpha therapy (TAT) in GEP-NENs patients. For instance, labeled technology and combination therapy could contribute to significantly improved long-term outcomes. However, the exact dosimetry for precision oncology, the shortage of radionuclides, and the stability of disease control are still under careful consideration. More high-quality, large-scale prospective studies are essential for obtaining valuable evidence on challenging problems and for further exploration.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"809-819"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic liquid biopsy of bile: superior diagnostic and prognostic performance of bile-derived exosomal miR-21-5p for biliary tract cancers.","authors":"Michihiro Yoshida, Tadashi Toyohara, Yasuki Hori, Akihisa Kato, Hidenori Sahashi, Kayoko Kuno, Akihisa Adachi, Yusuke Kito, Kenji Urakabe, Kazuki Hayashi, Itaru Naitoh, Fumihiro Okumura, Hiromu Kondo, Makoto Natsume, Naruomi Jinno, Kenta Kachi, Hiromi Kataoka, Yasuhito Tanaka","doi":"10.1007/s00535-025-02250-y","DOIUrl":"10.1007/s00535-025-02250-y","url":null,"abstract":"<p><strong>Background: </strong>Compared to peripheral blood, bile as a microenvironment within the biliary tract is expected to contain a higher concentration of tumor-associated factors secreted directly by primary biliary tumors, making it a promising source for tumor analysis. This study explores the diagnostic and prognostic utility of exosomal miR-21-5p in bile and serum for biliary tract cancers (BTCs).</p><p><strong>Methods: </strong>miR-21-5p expression was analyzed in 110 bile samples (55 BTC, 55 controls) collected during endoscopic retrograde cholangiopancreatography using qRT-PCR. The diagnostic and prognostic performances of miR-21-5p levels in bile and serum were evaluated. To enhance clinical applicability, we also developed a novel diagnostic parameter termed \"miR-21-5p bile/serum (B/S) ratio\", calculated by determining the ratio of bile to serum miR-21-5p within individuals.</p><p><strong>Results: </strong>miR-21-5p expression was significantly elevated in both the bile and serum of patients with BTC. Bile miR-21-5p showed superior diagnostic performance (AUC: 0.913) over serum miR-21-5p (AUC: 0.628) and CA19-9 (AUC: 0.793). Prognostically, a higher bile miR-21-5p was associated with poorer overall survival and was identified as an independent predictor (HR: 2.446, p = 0.002), whereas serum miR-21-5p lacked significant prognostic value. B/S ratio also showed high diagnostic accuracy when ≥ 2 (AUC: 0.870), and a B/S ratio ≥ 13 was associated with significantly poorer overall survival and found as an independent prognostic predictor (HR: 2.554, p = 0.008).</p><p><strong>Conclusions: </strong>Bile miR-21-5p and miR-21-5p B/S ratio are promising biomarkers for BTC diagnosis and prognosis that outperform traditional markers, highlighting the potential of bile-derived miRNAs for clinical use.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"905-916"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026500","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":"Identification of novel plasma proteins as promising noninvasive biomarker for early diagnosis and surveillance of pancreatic ductal adenocarcinoma.","authors":"Shuang Liu, Jiachun Su, Hongzhe Zhao, Ruihong Bai, Lingxing Zeng, Chunling Xue, Shuang Deng, Shaoqiu Liu, Ziming Chen, Zilan Xu, Yifan Zhou, Sihan Zhao, Xiaoyu Wu, Xinyi Peng, Jialiang Zhang, Xudong Huang, Jian Zheng, Chongyu Zhao, Lu Zheng","doi":"10.1007/s00535-025-02252-w","DOIUrl":"10.1007/s00535-025-02252-w","url":null,"abstract":"<p><strong>Background: </strong>Although cancer antigen 19-9 (CA 19-9) is the only FDA-approved biomarker for pancreatic ductal adenocarcinoma (PDAC), its diagnostic effectiveness is limited, as it may not be elevated in 15-25% of patients. This study aims to explore novel plasma proteins associated with PDAC as potential biomarkers for early diagnosis and clinical surveillance.</p><p><strong>Methods: </strong>Novel plasma protein biomarkers potentially causally associated with PDAC were identified using Mendelian randomization (MR). These biomarkers were validated in a multicenter study encompassing 230 tissue and 1,011 plasma samples to establish a diagnostic model for PDAC. Furthermore, their pre- and post-operative levels were compared to evaluate their potential as clinical surveillance biomarkers.</p><p><strong>Results: </strong>Genetically predicted expression of seven proteins potentially causally associated with an increased risk of PDAC. In a multicenter, large-scale study, Keratin 5 (KRT5) and Versican (VCAN) were identified as promising biomarkers for PDAC, with an area under the curve (AUC) of 0.90, and a combined panel including CA 19-9 achieved an AUC of 0.95. Additionally, plasma KRT5 and VCAN demonstrated superior diagnostic performance for early-stage PDAC with CA 19-9 levels below 37 U/mL (Stage I, AUC 0.85; Stage II, AUC 0.85). The specificity of plasma KRT5 and VCAN for PDAC was further validated by comparing their expression levels across various digestive cancers. Moreover, a significant decrease in plasma KRT5 and VCAN levels was observed post-surgery (P < 0.05), supporting their potential as biomarkers for clinical surveillance of PDAC.</p><p><strong>Conclusions: </strong>Plasma KRT5 and VCAN proteins may serve as promising valuable biomarkers for the early diagnosis and clinical surveillance of PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"917-931"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986338","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}