Clinics and research in hepatology and gastroenterology最新文献_第5页

Current advances in nanoparticle-based approaches for the hepatocellular carcinoma treatment 基于纳米颗粒的肝细胞癌治疗方法的进展。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102508

Sathishbabu Paranthaman , Umme Hani , Riyaz Ali M. Osmani , Rohit R. Bhosale , Nazima Haider

Hepatocellular carcinoma (HCC) is the most common form of liver (LC) with a high mortality rate, driven by risk factors including viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. The incident of HCC increases 2–4% of the worldwide population each year which would most certainly exceed one million per year by 2025. Despite advances in our knowledge, 25% of HCC tumors have actionable mutations which demands for innovative treatments strategies. In this perspective, we are providing a comprehensive summary of nanoparticles (NPs) based therapeutic approaches for HCC. We begin with an overview of HCC, concentrating on its pathogenesis, current conventional therapies, and their limitations. Then we delve into the therapeutic application of various nanoparticles (NPs) platforms for HCC, including polymeric micelles, dendrimers, liposomes, solid-lipid nanoparticles, nanostructured lipid carriers, exosomes, niosomes, mesoporous silica nanoparticles, carbon nanotubes. Special attention is given to the application of NPs in photothermal and photodynamic treatment was also investigated, with a focus on their effectiveness in targeted cancer ablation. Additionally, the review discusses recent patents and clinical studies that demonstrate the promise of NPs-based therapies in improving HCC treatment outcomes. This article underscores the potential of NPs based technologies to address the challenges faced by traditional therapies and offers insights into future directions for HCC management.

肝细胞癌（HCC）是最常见的肝脏（LC）形式，死亡率高，其危险因素包括病毒性肝炎、酒精性肝病和非酒精性脂肪性肝炎。HCC的发病率每年增加2-4%的世界人口，到2025年肯定会超过100万。尽管我们的知识有所进步，但25%的HCC肿瘤具有可操作的突变，这需要创新的治疗策略。从这个角度来看，我们提供了基于纳米颗粒（NPs）的HCC治疗方法的综合总结。我们首先概述HCC的发病机制、目前的常规治疗方法及其局限性。然后，我们深入研究了各种纳米颗粒（NPs）平台在HCC中的治疗应用，包括聚合物胶束、树突、脂质体、固体脂质纳米颗粒、纳米结构脂质载体、外泌体、乳泌体、介孔二氧化硅纳米颗粒、碳纳米管。特别关注NPs在光热和光动力治疗中的应用也进行了研究，重点是它们在靶向癌症消融中的有效性。此外，本综述还讨论了最近的专利和临床研究，这些研究表明基于nps的疗法有望改善HCC的治疗结果。本文强调了基于NPs的技术在解决传统疗法面临的挑战方面的潜力，并为HCC管理的未来方向提供了见解。

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引用次数: 0

Toward automated small bowel capsule endoscopy reporting using a summarizing machine learning algorithm: The SUM UP study 使用总结机器学习算法的自动小肠胶囊内窥镜报告：SUM UP研究。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102509

Charles Houdeville , Marc Souchaud , Romain Leenhardt , Lia CMJ Goltstein , Guillaume Velut , Hanneke Beaumont , Xavier Dray , Aymeric Histace

Background and objectives

Deep learning (DL) algorithms demonstrate excellent diagnostic performance for the detection of vascular lesions via small bowel (SB) capsule endoscopy (CE), including vascular abnormalities with high (P2), intermediate (P1) or low (P0) bleeding potential, while dramatically decreasing the reading time. We aimed to improve the performance of a DL algorithm by characterizing vascular abnormalities using a machine learning (ML) classifier, and selecting the most relevant images for insertion into reports.

Materials and methods

A training dataset of 75 SB CE videos was created, containing 401 sequences of interest that encompassed 1,525 images of various vascular lesions. Several image classification algorithms were tested, to discriminate “typical angiodysplasia” (P2/P1) and “other vascular lesion” (P0) and to select the most relevant image within sequences with repetitive images. The performances of the best-fitting algorithms were subsequently assessed on an independent test dataset of 73 full-length SB CE video recordings.

Results

Following DL detection, a random forest (RF) method demonstrated a specificity of 91.1 %, an area under the receiving operating characteristic curve of 0.873, and an accuracy of 84.2 % for discriminating P2/P1 from P0 lesions while allowing an 83.2 % reduction in the number of reported images. In the independent testing database, after RF was applied, the output number decreased by 91.6 %, from 216 (IQR 108–432) to 12 (IQR 5–33). The RF algorithm achieved 98.0 % agreement with initial, conventional (human) reporting. Following DL detection, the RF method allowed better characterization and accurate selection of images of relevant (P2/P1) SB vascular abnormalities for CE reporting without impairing diagnostic accuracy. These findings pave the way for automated SB CE reporting.

背景与目的：深度学习（DL）算法在小肠（SB）胶囊内窥镜（CE）血管病变检测中表现出优异的诊断性能，包括高（P2）、中（P1）或低（P0）出血潜能的血管异常，同时显著缩短了读取时间。我们的目标是通过使用机器学习（ML）分类器来表征血管异常，并选择最相关的图像插入到报告中，从而提高DL算法的性能。材料和方法：创建了一个包含75个SB CE视频的训练数据集，其中包含401个感兴趣序列，其中包含1,525张各种血管病变图像。测试了几种图像分类算法，以区分“典型血管发育不良”（P2/P1）和“其他血管病变”（P0），并在重复图像序列中选择最相关的图像。随后在73个完整的SB CE视频记录的独立测试数据集上评估了最佳拟合算法的性能。结果：DL检测后，随机森林（RF）方法的特异性为91.1%，接收工作特征曲线下面积为0.873，区分P2/P1和P0病变的准确率为84.2%，同时减少了83.2%的报告图像数量。在独立测试数据库中，应用射频后，输出数量减少了91.6%，从216个（IQR 108-432）减少到12个（IQR 5-33）。RF算法与初始的传统（人类）报告达到98%的一致性。在DL检测后，RF方法可以更好地表征和准确选择相关（P2/P1） SB血管异常的图像，用于CE报告，而不会损害诊断准确性。这些发现为自动化SB CE报告铺平了道路。

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引用次数: 0

Construction and validation of a machine learning-based prediction model for short-term mortality in critically ill patients with liver cirrhosis 基于机器学习的肝硬化危重患者短期死亡率预测模型的构建与验证。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102507

ZhanJin Wang , Fu Yuan Li , JunJie Cai , ZhangTuo Xue , Ying Zhou , Zhan Wang

Objective

Critically ill patients with liver cirrhosis generally have a poor prognosis due to complications such as multiple organ failure. This study aims to develop a machine learning-based prediction model to forecast short-term mortality in critically ill cirrhotic patients in the intensive care unit (ICU), thereby assisting clinical decision-making for intervention and treatment.

Methods

Machine learning models were developed using clinical data from critically ill cirrhotic patients in the MIMIC database, with multicenter validation performed using data from the eICU database and Qinghai University Affiliated Hospital(QUAH). Various machine learning models, including a Stacking ensemble model, were employed, with the SHAP method used to enhance model interpretability.

Results

The Stacking ensemble model demonstrated superior predictive performance through internal and external validation, with AUC and AP values surpassing those of individual algorithms. The AUC values were 0.845 in the internal validation set, 0.819 in the eICU external validation, and 0.761 in the QUAH validation set. Additionally, the SHAP method highlighted key prognostic variables such as INR, bilirubin, and urine output. The model was ultimately deployed as a web-based calculator for bedside decision-making.

Conclusion

The machine learning model effectively predicts short-term mortality risk in critically ill cirrhotic patients in the ICU, showing strong predictive performance and generalizability. The model's robust interpretability and its deployment as a web-based calculator suggest its potential as a valuable tool for assessing the prognosis of cirrhotic patients.

目的：肝硬化危重患者多器官功能衰竭等并发症，预后较差。本研究旨在建立一种基于机器学习的预测模型，预测重症监护病房（ICU）重症肝硬化患者的短期死亡率，从而辅助临床干预和治疗决策。方法：使用MIMIC数据库中重症肝硬化患者的临床数据建立机器学习模型，并使用eICU数据库和青海大学附属医院（QUAH）的数据进行多中心验证。采用了各种机器学习模型，包括堆叠集成模型，并使用了SHAP方法来增强模型的可解释性。结果：通过内部和外部验证，叠加集成模型显示出优越的预测性能，AUC和AP值超过单个算法。内部验证集的AUC值为0.845，eICU外部验证集的AUC值为0.819，QUAH验证集的AUC值为0.761。此外，SHAP方法强调了关键的预后变量，如INR、胆红素和尿量。该模型最终被部署为一个基于网络的床边决策计算器。结论：该机器学习模型可有效预测ICU重症肝硬化患者短期死亡风险，具有较强的预测性能和通用性。该模型强大的可解释性及其作为基于网络的计算器的部署表明，它有潜力成为评估肝硬化患者预后的有价值工具。

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引用次数: 0

A heterogeneous subtype of biliary epithelial senescence may be involved in the pathogenesis of primary biliary cholangitis 胆道上皮衰老的异质性亚型可能参与原发性胆道胆管炎的发病机制。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102512

Motoko Sasaki , Yasunori Sato , Yasuni Nakanuma

Background & aims

Biliary epithelial senescence is involved in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that a unique subtype of programmed death-ligand 1 (PD-L1)-positive senescent biliary epithelial cells (BECs) may be related to the pathogenesis of PBC in association with cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) pathway.

Approach & results

The expression of PD-L1, STING and their association with senescent markers p16^INK4a and p21^WAF1/Cip1 were immunohistochemically determined in livers taken from the patients with PBC (n = 87) and 97 diseased and normal control livers. The expression of PD-L1 was significantly increased in a part of senescent BECs with p21^WAF1/Cip1 expression in BECs in the damaged small bile ducts in PBC, compared to control livers (p < 0.01). In contrast, PD-L1 was not expressed in BECs in ductular reactions. The expression of STING was significantly increased in BECs in small bile ducts and ductular reactions in PBC, compared to control livers (p < 0.01). The expression of PD-L1, STING and senescence associated secretory phenotypes (SASPs) including interferon (IFN)-beta was significantly increased in senescent BECs induced by a treatment with serum depletion or glycochenodeoxycholic acid (GCDC) for 4–7 days (p < 0.01) and the increase was significantly suppressed by a knockdown of STING using siRNA (p < 0.01). Induction of cellular senescence induced by a treatment with serum depletion or GCDC was significantly suppressed by a knockdown of STING in BECs. (p < 0.01).

Conclusion

A unique subtype of senescent BECs with PD-L1 expression associated with cGAS-STING pathway may be involved in the pathogenesis of PBC.

背景与目的：胆道上皮衰老参与原发性胆道胆管炎（PBC）的发病机制。我们假设程序性死亡配体1 （PD-L1）阳性的衰老胆道上皮细胞（BECs）的一个独特亚型可能与PBC的发病机制有关，该亚型与环GMP-AMP合成酶(cGAS)-干扰素基因刺激因子（STING）通路有关。方法与结果：采用免疫组织化学方法检测了PBC患者（87例）和97例患病及正常对照肝脏中PD-L1、STING的表达及其与衰老标志物p16INK4a和p21WAF1/Cip1的关系。与对照组相比，PBC受损小胆管中部分表达p21WAF1/Cip1的衰老BECs中PD-L1的表达显著升高(PBC结论：一种独特的与cGAS-STING通路相关的PD-L1表达的衰老BECs亚型可能参与了PBC的发病机制。

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引用次数: 0

α-L-Fucosidase: A potential biomarker for differential diagnosis of autoimmune hepatitis and drug-induced autoimmune hepatitis α-L-聚焦酶：自身免疫性肝炎和药物性自身免疫性肝炎鉴别诊断的潜在生物标志物

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102517

Yingying Lin , Xinyu Cui , Yanyan Li , Na Zhu , Xin Li

引用次数: 0

An ileo-anal pouch doing the twist (with video) 回肠肛管做扭转（有视频）。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102511

Flore de Castelbajac, Nicolas Billet, Laurence Monnier-Chollet, Aziz Zaanan, Philippe Seksik, Xavier Dray

A 37-year-old female patient had a past history of proctocolectomy for Crohn's disease, with ileal J-pouch-anal anastomosis. She was admitted for acute obstructive symptoms. CT scan revealed a 180 twisted ileo-anal anastomosis without signs of severe ischemia (Fig. 1 and video), prompting urgent endoscopic treatment. Lower endoscopy showed a complete spiral of the J-pouch which was easily untwisted and passed. Aspiration followed by placement of a multiperforated Faucher tube allowed immediate symptoms relief. The tube was withdrawn 2 days later and the patient was discharged on the same evening. Although the patient was warned for recurrences, no further episode had occurred at last (60 days) follow-up.

The term "twisted syndrome" refers to the twisting of the ileal pouch around its mesenteric axis, creating a volvulus, possibly leading to acute intestinal obstruction. It is often caused by insufficient adhesion of the ileum to the pelvis or to excessive length of the mesentery. If untreated, the twist can disrupt vascularization, leading to pouch ischemia and necrosis. The treatment typically involves emergency endoscopy to untwist the pouch whereas redo pouch-surgery should be discussed to prevent future episodes. Other mechanisms of pouch obstruction include prolapse (also known as “floppy pouch complex”) [2], inflammation, fibrosis, dysplasia or cancer related to inflammatory bowel disease, or rare extraluminal causes.

This case highlights the importance of combining emergency CT-scan and endoscopy to diagnose various pouch complications, to untwist the pouch in case of a volvulus, and to enhance the strategy for pouch salvage. Three-dimensional CT-based pouchography is also an advanced option to better guide decisions [3].

37岁女性，既往因克罗恩病行直结肠切除术，回肠j袋-肛门吻合术。她因急性阻塞性症状入院CT扫描显示回肠肛管吻合口180度扭曲，无严重缺血征象（图1和视频），提示紧急内镜治疗。下内镜显示j型囊呈完整螺旋状，易解扭并通过。抽吸后置入多孔福氏管可立即缓解症状。2天后拔管，当晚出院。虽然患者被警告复发，但在最后（60天）随访中没有再发生。“扭转综合征”是指回肠囊绕肠系膜轴扭曲，造成肠扭转，可能导致急性肠梗阻。它通常是由回肠与骨盆粘连不足或肠系膜过长引起的。如果不及时治疗，扭曲会破坏血管形成，导致眼袋缺血和坏死。治疗通常包括紧急内窥镜检查来解开眼袋，而重做眼袋手术应该讨论，以防止未来的发作。眼袋梗阻的其他机制包括脱垂（也称为“软眼袋复合物”）、炎症、纤维化、发育不良或与炎症性肠病相关的癌症，或罕见的腔外原因。本病例强调了急诊ct扫描和内窥镜检查结合诊断各种眼袋并发症的重要性，在扭转的情况下解开眼袋，并加强眼袋抢救策略。三维ct成像也是一种高级选择，可以更好地指导决策。

{"title":"An ileo-anal pouch doing the twist (with video)","authors":"Flore de Castelbajac, Nicolas Billet, Laurence Monnier-Chollet, Aziz Zaanan, Philippe Seksik, Xavier Dray","doi":"10.1016/j.clinre.2024.102511","DOIUrl":"10.1016/j.clinre.2024.102511","url":null,"abstract":"<div><div>A 37-year-old female patient had a past history of proctocolectomy for Crohn's disease, with ileal J-pouch-anal anastomosis. She was admitted for acute obstructive symptoms. CT scan revealed a 180 twisted ileo-anal anastomosis without signs of severe ischemia (<span><span>Fig. 1</span></span> <strong>and video</strong>), prompting urgent endoscopic treatment. Lower endoscopy showed a complete spiral of the J-pouch which was easily untwisted and passed. Aspiration followed by placement of a multiperforated Faucher tube allowed immediate symptoms relief. The tube was withdrawn 2 days later and the patient was discharged on the same evening. Although the patient was warned for recurrences, no further episode had occurred at last (60 days) follow-up.</div><div>The term \"twisted syndrome\" refers to the twisting of the ileal pouch around its mesenteric axis, creating a volvulus, possibly leading to acute intestinal obstruction. It is often caused by insufficient adhesion of the ileum to the pelvis or to excessive length of the mesentery. If untreated, the twist can disrupt vascularization, leading to pouch ischemia and necrosis. The treatment typically involves emergency endoscopy to untwist the pouch whereas redo pouch-surgery should be discussed to prevent future episodes. Other mechanisms of pouch obstruction include prolapse (also known as “floppy pouch complex”) [2], inflammation, fibrosis, dysplasia or cancer related to inflammatory bowel disease, or rare extraluminal causes.</div><div>This case highlights the importance of combining emergency CT-scan and endoscopy to diagnose various pouch complications, to untwist the pouch in case of a volvulus, and to enhance the strategy for pouch salvage. Three-dimensional CT-based pouchography is also an advanced option to better guide decisions [3].</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 1","pages":"Article 102511"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The flaming and pulled up anorectal line: Ulcerative colitis-associated squamous metaplasia of the lower rectum 燃烧和拉起的肛肠线：溃疡性结肠炎相关的下直肠鳞状皮化生。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102513

Vincent Zimmer

引用次数: 0

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A systematic review and meta-analysis 肿瘤浸润淋巴细胞在胃癌预后中的作用：一项系统综述和荟萃分析。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102510

Xiaoqing Cao , Yurou Kang , Ping Tai, Pei Zhang, Xin Lin, Fei Xu, Zhenlin Nie, Bangshun He

Background

To analyze the relationship between tumor-infiltrating lymphocytes (TILs) subtypes and infiltration locations and the prognosis of gastric cancer (GC) patients.

Methods

Eligible articles were obtained through systematic retrieval and rigorous screening, collecting study information and extracting hazard ratio (HR), 95 % confidence interval (CI) for pooled analyses of disease-free survival (DFS) and overall survival (OS).

Results

Higher CD4⁺ TILs were correlated with favorable OS (HR=0.79, 95 %CI: 0.66–0.94, P = 0.009), the similar results were observed in tumor center and in infiltration margin. Higher CD8⁺ TILs prolonged DFS (HR=0.69, 95 %CI: 0.51–0.95, P = 0.02) and OS (HR=0.96, 95 %CI: 0.94–0.99, P = 0.006); For OS, tumor center and infiltration margin groups showed positive results. Neither the overall analysis nor the subgroup analyses indicated that the level of FOXP3⁺ TILs was associated with prognosis (DFS: HR=0.89, 95 %CI: 0.66–1.19, P = 0.42; OS: HR=0.98, 95 %CI: 0.85–1.13, P = 0.75). Pooled results revealed that higher CD3⁺ TILs were correlated with favorable DFS (HR=0.69, 95 %CI: 0.56–0.84, P = 0.0003) but not OS (HR=1.00, 95 %CI: 0.99–1.01, P = 0.48).

Conclusions

High infiltrating CD3⁺, CD4⁺, CD8⁺ T cells prolong survival, and FOXP3⁺ subset is not related to prognosis in GC. For CD4⁺ and CD8⁺, positive correlations between the infiltration level and OS were present in tumor center and infiltration margin groups.

背景：分析胃癌（GC）患者肿瘤浸润淋巴细胞（tumor-浸润淋巴细胞，TILs）亚型及浸润部位与预后的关系。方法：通过系统检索和严格筛选，收集研究信息，提取风险比（HR）和95%置信区间（CI），对无病生存期（DFS）和总生存期（OS）进行合并分析，获得符合条件的文献。结果：CD4+ TILs越高，OS越好（HR=0.79, 95%CI: 0.66 ~ 0.94， P=0.009），肿瘤中心和浸润边缘的结果相似。较高的CD8+ TILs延长DFS （HR=0.69, 95%CI: 0.51 ~ 0.95， P=0.02）和OS (HR=0.96, 95%CI: 0.94 ~ 0.99， P=0.006)；肿瘤中心组和浸润边缘组OS阳性。总体分析和亚组分析均未显示FOXP3+ TILs水平与预后相关(DFS: HR=0.89, 95%CI: 0.66-1.19， P=0.42；Os: hr =0.98, 95%ci: 0.85-1.13, p =0.75)。综合结果显示，较高的CD3+ TILs与较好的DFS相关（HR=0.69, 95%CI: 0.56 ~ 0.84， P=0.0003），但与OS无关（HR=1.00, 95%CI: 0.99 ~ 1.01， P=0.48）。结论：高浸润的CD3+、CD4+、CD8+ T细胞延长了胃癌患者的生存期，FOXP3+亚群与预后无关。肿瘤中心组和浸润边缘组CD4+、CD8+浸润水平与OS呈正相关。

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引用次数: 0

Exploring gender disparities in hepatocellular carcinoma: Insights from a French study 探讨肝细胞癌的性别差异：来自法国研究的见解。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102518

Héloïse Giudicelli, Manon Allaire

引用次数: 0

Telomere-methylation genes: Novel prognostic biomarkers for hepatocellular carcinoma 端粒甲基化基因：肝细胞癌的新型预后生物标志物

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology

Pub Date : 2025-01-01 DOI: 10.1016/j.clinre.2024.102516

Jia-Wen Xie , Hui-Ling Wang , Ling-Qing Lin , Yin-Feng Guo , Mao Wang , Xiao-Zhen Zhu , Jian-Jun Niu , Li-Rong Lin

Background

Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.

Method

This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.

Result

The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.

Conclusion

This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.

背景：由于端粒长度和DNA甲基化都与肝细胞癌（HCC）的预后相关，端粒甲基化基因可能成为HCC预后的新标志物。方法：本研究首先通过孟德尔随机化分析研究HCC端粒长度与DNA甲基化之间的相互作用。随后，本研究利用TCGA-LIHC队列技术鉴定HCC中端粒甲基化基因，并探讨这些基因在HCC肿瘤微环境中的表达模式及其潜在机制。最后建立基于这些基因的HCC风险评分模型和预后模型，并对模型的性能进行评估。结果：发现端粒长度和DNA甲基化在HCC中存在双向关系。共鉴定出50个端粒甲基化基因，其中与预后相关的端粒甲基化基因与HCC肿瘤微环境中的Treg和tproif细胞亚群密切相关。端粒甲基化基因可能通过调节染色体稳定性和细胞周期影响HCC患者的预后。此外，构建的风险评分模型和预后预测模型的临床适用性较强，从受试者工作特征曲线、决策曲线分析和校准曲线均可看出。结论：本研究阐明了端粒甲基化基因作为HCC预后生物标志物的潜力，为HCC患者预后和治疗管理的新方法铺平了道路。

{"title":"Telomere-methylation genes: Novel prognostic biomarkers for hepatocellular carcinoma","authors":"Jia-Wen Xie , Hui-Ling Wang , Ling-Qing Lin , Yin-Feng Guo , Mao Wang , Xiao-Zhen Zhu , Jian-Jun Niu , Li-Rong Lin","doi":"10.1016/j.clinre.2024.102516","DOIUrl":"10.1016/j.clinre.2024.102516","url":null,"abstract":"<div><h3>Background</h3><div>Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.</div></div><div><h3>Method</h3><div>This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.</div></div><div><h3>Result</h3><div>The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.</div></div><div><h3>Conclusion</h3><div>This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.</div></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"49 1","pages":"Article 102516"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0