• 文章类型: Journal Article
    常规进行远端胃切除术(DG)和淋巴结清扫术治疗胃癌。在这个荟萃分析中,我们提供了腹腔镜DG(LDG)和机器人DG(RDG)的围手术期和肿瘤学结局的最新概述,以比较DG患者的安全性和总体结局.使用MEDLINE进行了广泛的搜索,EMBASE,PubMed,WebofScience,从数据库建立到2023年6月,Cochrane中央对照试验登记册用于比较RDG和LDG的随机临床试验。主要结果是手术结果,术后恢复,并发症,切除的充分性,和长期生存。我们确定了20项研究,评估5,447例患者(1,968例和3,479例接受RDG和LDG治疗的患者,分别)。我们观察到两组在近端切缘方面无显著差异,解剖的淋巴结数量,主要并发症,吻合部位渗漏,时间到了第一次排气,和住院时间。RDG组手术时间较长(P<0.00001),出血较少(P=0.0001),远端切除边缘较长(P=0.02),较早的口服时间(P=0.02),总体并发症较少(P=0.004),且费用高于LDG组(P<0.0001)。由于可接受的并发症和根治性切除的可能性,RDG是改善LDG的有前途的方法。更长的手术时间和更高的成本不应该阻止研究人员探索机器人手术的新应用。
    Distal gastrectomy (DG) with lymph node dissection for gastric cancer is routinely performed. In this meta-analysis, we present an updated overview of the perioperative and oncological outcomes of laparoscopic DG (LDG) and robotic DG (RDG) to compare their safety and overall outcomes in patients undergoing DG. An extensive search was conducted using the MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from the establishment of the database to June 2023 for randomized clinical trials comparing RDG and LDG. The primary outcome was operative results, postoperative recovery, complications, adequacy of resection, and long-term survival. We identified twenty studies, evaluating 5,447 patients (1,968 and 3,479 patients treated with RDG and LDG, respectively). We observed no significant differences between the two groups in terms of the proximal resection margin, number of dissected lymph nodes, major complications, anastomosis site leakage, time to first flatus, and length of hospital stay. The RDG group had a longer operative time (P < 0.00001), lesser bleeding (P = 0.0001), longer distal resection margin (P = 0.02), earlier time to oral intake (P = 0.02), fewer overall complications (P = 0.004), and higher costs (P < 0.0001) than the LDG group. RDG is a promising approach for improving LDG owing to acceptable complications and the possibility of radical resection. Longer operative times and higher costs should not prevent researchers from exploring new applications of robotic surgery.
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  • 文章类型: Journal Article
    目的/背景特质情绪智力与癌症患者的焦虑和抑郁症状以及生活质量相关。然而,关于特质情绪智力与焦虑关系的研究,抑郁症,胃癌患者的生活质量有限。本研究探讨胃癌患者特质情绪智力与抑郁情绪及生活质量的关系,为临床管理提供理论依据。方法选取2020年7月至2023年7月我院收治的270例胃癌患者,其中筛选出31例问卷缺失和漏诊的患者,结果纳入了239名胃癌患者。在这次调查中,自我管理的一般信息问卷,即特质情绪智力简称(TEIQue-SF),欧洲癌症研究和治疗组织的生活质量问卷-核心30(EORTCQLQ-C30),使用医院焦虑和抑郁量表(HADS)。结果TEIQue-SF总分与QLQ-C30得分呈正相关(p<0.001),与HADS-A、HADS-D得分呈负相关(p<0.001)。TEIQue-SF总分是QLQ-C30评分的阳性预测因子(β=0.412,p<0.001)和HADS评分的阴性预测因子(β=-0.740,p<0.001)。TEIQue-SF总分(β=0.141,p=0.006)和HADS评分(β=-0.665,p<0.001)是QLQ-C30评分的良好预测因子。TEIQue-SF总分对QLQ-C30评分的直接影响为0.141,而TEIQQUE-SF总分与QLQ-C30评分之间的HADS评分的介导效应值为0.492。结论特质情绪智力不仅直接影响生活质量,但也通过焦虑和抑郁间接影响生活质量。临床医生应该注意焦虑,抑郁症,提高胃癌患者的生活质量。
    Aims/Background Trait emotional intelligence is associated with anxiety and depression symptoms and quality of life in cancer patients. However, studies on the relationship of trait emotional intelligence with anxiety, depression, and quality of life in gastric cancer patients are limited. This study investigates the relationship of trait emotional intelligence with depression and quality of life in gastric cancer patients to provide a theoretical basis for clinical management. Methods A total of 270 patients with gastric cancer treated in our hospital from July 2020 to July 2023 were selected, of which 31 patients with missing questionnaire entries and missed visits were screened out, resulting in the enrolment of 239 gastric cancer patients in this study. In this survey, self-administered general information questionnaires, namely Trait Emotional Intelligence Short Form (TEIQue-SF), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) were used. Results TEIQue-SF total scores were positively correlated with QLQ-C30 scores (p < 0.001) and negatively correlated with HADS-A and HADS-D scores (p < 0.001). TEIQue-SF total score was a superior positive predictor of the QLQ-C30 score (β = 0.412, p < 0.001) and a superior negative predictor of the HADS score (β = -0.740, p < 0.001). TEIQue-SF total score (β = 0.141, p = 0.006) and HADS score (β = -0.665, p < 0.001) were good predictors of QLQ-C30 score. The direct effect of TEIQue-SF total score on QLQ-C30 score was 0.141, while HADS score between TEIQue-SF total score and QLQ-C30 score had a mediated effect value of 0.492. Conclusion Trait emotional intelligence not only directly affects the quality of life, but also indirectly affects the quality of life through anxiety and depression. Clinicians should pay attention to the anxiety, depression, and emotional intelligence of patients with gastric cancer to help them improve their quality of life.
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  • 文章类型: Journal Article
    背景:肌肉减少性肥胖(SO)影响各种恶性肿瘤的预后。然而,其在接受新辅助化疗(NAC)治疗局部进展期胃癌(LAGC)患者中的临床意义尚不清楚.这项研究调查了NAC前后SO对术后发病率和生存率的影响。
    方法:来自207例LAGC患者的数据,在2010年1月至2019年10月期间接受NAC后接受根治性胃切除术的患者进行了回顾性分析.使用计算机断层扫描在NAC前后测量骨骼肌质量和内脏脂肪面积,以定义肌肉减少症和肥胖。共存的定义为SO。
    结果:在患者中,52(25.1%)和38(18.4%)在NAC前后发展了SO,分别。术前(34.6%)和术后(47.4%)NACSO与术后发病率最高相关;然而,仅NAC后SO是术后发病率的独立危险因素[风险比(HR)=9.550,95%置信区间(CI)=2.818-32.369;P<.001].NAC前的SO与较差的3年总体独立相关[46.2%与61.3%;HR=1.258(95%CI=1.023-1.547);P=.049]且无复发[39.3%vs.55.4%;HR1.285(95%CI1.045-1.579);P=0.017]生存率。
    结论:Pre-NACSO是接受NAC的LAGC患者的独立预后因素;NAC后SO独立预测术后发病率。
    BACKGROUND: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival.
    METHODS: Data from 207 patients with LAGC, who underwent NAC followed by radical gastrectomy between January 2010 and October 2019, were reviewed. Skeletal muscle mass and visceral fat area were measured pre- and post-NAC using computed tomography to define sarcopenia and obesity, the coexistence of which was defined as SO.
    RESULTS: Among the patients, 52 (25.1%) and 38 (18.4%) developed SO before and after NAC, respectively. Both pre- (34.6%) and post- (47.4%) NAC SO were associated with the highest postoperative morbidity rates; however, only post-NAC SO was an independent risk factor for postoperative morbidity [hazard ratio (HR) = 9.550, 95% confidence interval (CI) = 2.818-32.369; P < .001]. Pre-NAC SO was independently associated with poorer 3-year overall [46.2% vs. 61.3%; HR = 1.258 (95% CI = 1.023-1.547); P = .049] and recurrence-free [39.3% vs. 55.4%; HR 1.285 (95% CI 1.045-1.579); P = .017] survival.
    CONCLUSIONS: Pre-NAC SO was an independent prognostic factor in patients with LAGC undergoing NAC; post-NAC SO independently predicted postoperative morbidity.
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  • 文章类型: Journal Article
    胃癌根治术后并发症严重影响术后恢复,需要准确预测风险。因此,本研究旨在开发一种预测模型,用于指导胃癌患者围手术期并发症的临床决策.回顾性分析2022年4月至2023年6月在南京医科大学第一附属医院行胃癌根治术的患者。共纳入166例患者。患者人口学特征,实验室检查结果,并记录手术病理特征。术前腹部CT扫描通过3Dslicer对患者的内脏脂肪区域进行分割,采用3D卷积神经网络(3D-CNN)提取图像特征,并采用LASSO回归模型进行特征选择。此外,采用集成学习策略训练胃癌的特征并预测术后并发症。LGBM(光梯度升压机)的预测性能,XGB(XGBoost),RF(随机森林),通过五次交叉验证对GBDT(梯度提升决策树)模型进行了评估。本研究成功构建了基于优化算法的胃癌根治术后早期并发症预测模型,LGBM.LGBM模型的AUC值为0.9232,准确率为87.28%(95%CI,75.61-98.95%),超越其他型号的性能。通过对围手术期临床数据和内脏脂肪影像组学的集成学习和整合,建立了预测LGBM模型。该模型有可能促进胃癌术后患者的个体化临床决策和早期康复。
    Postoperative complications of radical gastrectomy seriously affect postoperative recovery and require accurate risk prediction. Therefore, this study aimed to develop a prediction model specifically tailored to guide perioperative clinical decision-making for postoperative complications in patients with gastric cancer. A retrospective analysis was conducted on patients who underwent radical gastrectomy at the First Affiliated Hospital of Nanjing Medical University between April 2022 and June 2023. A total of 166 patients were enrolled. Patient demographic characteristics, laboratory examination results, and surgical pathological features were recorded. Preoperative abdominal CT scans were used to segment the visceral fat region of the patients through 3Dslicer, a 3D Convolutional Neural Network (3D-CNN) to extract image features and the LASSO regression model was employed for feature selection. Moreover, an ensemble learning strategy was adopted to train the features and predict postoperative complications of gastric cancer. The prediction performance of the LGBM (Light Gradient Boosting Machine), XGB (XGBoost), RF (Random Forest), and GBDT (Gradient Boosting Decision Tree) models was evaluated through fivefold cross-validation. This study successfully constructed a model for predicting early complications following radical gastrectomy based on the optimal algorithm, LGBM. The LGBM model yielded an AUC value of 0.9232 and an accuracy of 87.28% (95% CI, 75.61-98.95%), surpassing the performance of other models. Through ensemble learning and integration of perioperative clinical data and visceral fat radiomics, a predictive LGBM model was established. This model has the potential to facilitate individualized clinical decision-making and the early recovery of patients with gastric cancer post-surgery.
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  • 文章类型: Journal Article
    胃癌(GC)是全球癌症相关死亡的主要原因。这种癌症是由多种(epi)遗传和环境因素决定的;可以发生在胃的不同解剖位置;并显示高度异质性,具有不同的细胞起源和不同的组织学和分子特征。这种异质性阻碍了充分理解GC病理学和开发有效疗法的努力。在过去的十年里,气相色谱法的研究取得了很大进展,特别是在分子亚型中,免疫微环境的调查,定义进化路径和动力学。临床前小鼠模型,特别是模拟人类GC的细胞和分子特征的免疫能力模型,结合类器官培养和临床研究,为阐明GC病理学和免疫逃避的分子和细胞机制提供了强大的工具,以及新型治疗策略的发展。在这里,我们首先简要介绍GC研究的进展和挑战,然后总结免疫活性GC小鼠模型,强调基因工程小鼠模型在抗肿瘤免疫和免疫治疗研究中的潜在应用。
    Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. This cancer is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.
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  • 文章类型: Journal Article
    胃微生物群落在胃癌(GC)中起着基础性作用,以及GC的两种主要解剖亚型,非贲门和贲门GC,与不同的危险因素(非贲门GC的幽门螺杆菌)相关。为了破译GC的不同微生物空间群落,我们进行了多中心回顾性分析,以表征223例GC患者的胃微生物群,包括幽门螺杆菌阳性或阴性患者,肿瘤和配对的邻近正常组织,使用第三代测序。在独立验证队列中,收集牙菌斑和GC肿瘤组织样本并进行测序.在GC肿瘤组织和匹配的非肿瘤组织中,使用荧光原位杂交(FISH)测定法验证了幽门螺杆菌和口腔相关细菌的患病率。我们发现胃微生物群的垂直分布,在上层,中间,和较低的第三个GC站点,可能是引起GC肿瘤组织中微生物多样性的重要因素。口腔相关微生物群集群,其中包括小维罗氏菌,口链球菌,和中间的普雷沃特拉,在GC的上三分之一中更为丰富。然而,幽门螺杆菌在GC的下三分之一中更丰富,并表现出明显的高度微生物相关性。口腔相关的微生物群模块与幽门螺杆菌在GC肿瘤组织的较低的第三个部位是共同排斥的。重要的是,幽门螺杆菌阴性GC患者与口腔相关的胃微生物群显示较差的总生存率,而幽门螺杆菌阳性GC患者中微生物丰度的增加显示总生存期无差异。在独立的验证阶段,牙菌斑和GC组织样本中细小弧菌的患病率是一致的。我们表明,口腔相关物种细小弧菌和口腔链球菌与总体生存率相关。我们的研究强调了口腔相关微生物群在GC的上三分之一中的作用。此外,口腔相关物种可作为治疗GC的非侵入性筛查工具,也是幽门螺杆菌阴性GC的独立预后因素.
    目的:我们的研究强调了口腔相关微生物群在上三分之一胃癌(GC)中的作用。我们表明,与口腔相关的物种小静脉菌和口腔链球菌与总体生存率相关。此外,口腔相关物种可作为治疗GC的非侵入性筛查工具,也是幽门螺杆菌阴性GC的独立预后因素.
    The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.
    OBJECTIVE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.
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  • 文章类型: Retraction of Publication
    在本文发表之后,有关读者注意到,无花果中显示的某些数据引起了编辑的注意。2A和4F与由不同研究机构的不同作者撰写的其他文章中以不同形式出现的数据惊人地相似,这些文章大约在同一时间提交给各自的期刊;此外,同样的数据显然也包括在图中的西方印迹中。图5A显示Parkin和mito‑LCIII蛋白带。由于不清楚这里提交惊人相似数据的原始地点是什么,编辑要求作者向我们发送受影响数字的所有原始数据;然而,提交人在询问时未能遵守这一要求。鉴于作者无法按要求提供支持数据,由于对所提供的数据缺乏信心,《国际肿瘤学杂志》的编辑已决定将这篇论文从该杂志撤回.作者被要求解释这些担忧,但是编辑部没有得到满意的答复。编辑对读者造成的不便表示歉意。[国际肿瘤学杂志52:367-378,2018;DOI:10.3892/ijo.2017.4216]。
    Following the publication of this paper, it was drawn to the Editor\'s attention by a concerned reader that certain of the data shown in Figs. 2A and 4F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that were submitted to their respective journals at around the same time; moreover, the same data had apparently been included in the western blots featured in Fig. 5A to show the Parkin and mito‑LCIII protein bands. As it was not clear what had been the original venue for the submission of the strikingly similar data here, the Editor requested that the authors send to us all the raw data underlying the affected figures; however, the authors were not able to comply with this request at the time of asking. Given that the authors were unable to provide the supporting data as requested, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 52: 367‑378, 2018; DOI: 10.3892/ijo.2017.4216].
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  • 文章类型: Journal Article
    背景:胃癌(GC)是全球癌症相关死亡的主要原因。其分子机制,特别是关于自噬和各种信号通路,没有完全理解。脂肪酸结合蛋白6(FABP6)和RE1沉默转录因子(REST)在这种情况下成为潜在的关键参与者。本研究旨在分析FABP6和REST与自噬的功能关系及其对GC细胞内Akt/mTOR信号通路的影响。
    方法:使用综合生物信息学方法来鉴定GC的关键预后标志物。通过包括蛋白质印迹(WB)在内的技术分析了FABP6和REST对自噬以及Akt/mTOR信号通路的影响。流式细胞术,Transwell分析,双荧光素酶报告分析,和其他人。
    结果:FABP6在GC中被鉴定为过表达,与预后不良有关。FABP6沉默降低GC细胞增殖,引起S-和G2-阶段停滞,并下调细胞周期蛋白CDK2和CDK4。它还抑制GC细胞侵袭/迁移和自噬,MG132抵消的影响。当与PI3K抑制剂LY294002c联合使用时,FABP6敲低显示协同抗增殖作用,调节Akt/mTOR途径。此外,转录因子REST已被证明直接调节FABP6的表达,以FABP6依赖性方式影响自噬和Akt/mTOR信号通路。
    结论:REST正向调节自噬,并以FABP6依赖性方式对GC细胞中的Akt/mTOR信号通路产生负面影响,为涉及FABP6和REST的监管网络提供有价值的见解。
    BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways, are not fully understood. Fatty Acid Binding Protein 6 (FABP6) and RE1 Silencing Transcription Factor (REST) emerge as potential key players in this context. This study sought to analyze the functional relationship of FABP6 and REST concerning autophagy and their implications on the Akt/mTOR signaling pathway within GC cells.
    METHODS: A comprehensive bioinformatics approach was used to identify key prognostic markers in GC. The effects of FABP6 and REST on autophagy along with Akt/mTOR signaling pathways were analyzed by techniques including Western blotting (WB), flow cytometry, Transwell assay, dual luciferase reporter assay, and others.
    RESULTS: FABP6 was identified as overexpressed in GC, linked with poor prognosis. FABP6 silencing reduces GC cell proliferation, induces S- and G2-phase arrest, and downregulates cyclins CDK2 and CDK4. It also inhibited GC cell invasion/migration and autophagy, effects that were counteracted by MG132. When combined with PI3K inhibitor LY294002c, FABP6 knockdown showed synergistic anti-proliferative effects, modulating the Akt/mTOR pathway. Besides, the transcription factor REST has been shown to directly regulate FABP6 expression, affecting autophagy and the Akt/mTOR signaling pathway in a FABP6-dependent manner.
    CONCLUSIONS: REST positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving FABP6 and REST.
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  • 文章类型: Journal Article
    背景:本研究旨在开发一种新型的六基因表达生物标志物组,以增强局部晚期胃癌(LAGC)腹膜复发和微转移的早期检测和风险分层。
    方法:我们使用全基因组转录组分析和严格的生物信息学来鉴定六基因表达生物标志物组。使用组织和液体活检样本在多个临床队列中验证了该小组,以预测LAGC患者的腹膜复发和微转移。
    结果:通过全基因组表达谱,我们鉴定了6个mRNAs,并使用来自手术样本训练队列的196个样本建立了风险预测模型.这个模型,纳入具有临床特征的6-mRNA组,对胃癌患者的腹膜复发具有很高的预测准确性,AUC为0.966(95%CI:0.944-0.988)。从侵入性手术或内窥镜活检过渡到非侵入性液体活检,该模型保留了其预测功效(AUC=0.963;95%CI:0.926-1.000).此外,在95例外周血标本中,6-mRNA组有效区分有或无腹膜转移的患者(AUC=0.970;95%CI:0.936-1.000),并高效鉴定腹膜微转移(AUC=0.941;95%CI:0.874-1.000).
    结论:我们的研究提供了一个新的基因表达生物标志物组,可显著提高LAGC患者腹膜复发和微转移的早期检测。RSA模型的预测能力为量身定制的治疗策略提供了一个有前途的工具,强调在精准肿瘤学中整合分子生物标志物与临床参数的重要性。
    BACKGROUND: This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC).
    METHODS: We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC.
    RESULTS: Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000).
    CONCLUSIONS: Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model\'s predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.
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  • 文章类型: Journal Article
    目的:泛素特异性肽酶10(USP10),一种典型的去泛素酶,已被发现在人类癌症中起着双重作用。以前,我们报道USP10的表达与胃壁浸润深度呈负相关,淋巴结转移,胃癌(GC)患者的预后。然而,目前尚不清楚USP10是否可以通过其去泛素化功能调节GC细胞的转移。
    方法:在本研究中,蛋白质组,泛素组,并进行转录组分析以全面鉴定GC细胞中USP10的新型去泛素化靶标。随后,一系列验证实验,包括体外细胞培养研究,体内转移肿瘤模型,和临床样本分析,进行以阐明USP10及其去泛素化靶标在GC转移中的调节机制。
    结果:在GC细胞中过表达USP10后,146种蛋白质,489个泛素位点,61个mRNA表现出差异表达。通过整合多组学的结果,我们最终筛选了USP10的9种潜在底物,包括TNFRSF10B,SLC2A3、CD44、CSTF2、RPS27、TPD52、GPS1、RNF185和MED16。其中,通过Co-IP和蛋白质稳定化测定进一步证实TNFRSF10B是USP10的直接去泛素化靶标。在体外和体内模型中,USP10或TNFRSF10B的失调影响了GC细胞的迁移和侵袭。分子机制研究表明,USP10通过增加TNFRSF10B蛋白的稳定性抑制上皮间质转化(EMT)过程,从而调控GC细胞的迁徙和侵袭。最后,回顾性临床样本研究表明,TNFRSF10B表达的下调与7个GC队列中的4个患者的低生存率相关,TNFRSF10B蛋白的表达与远处转移的发生率呈显著负相关,漫反射类型,和粘性差的癌。
    结论:我们的研究建立了筛选USP10去泛素化靶标的高通量策略,并进一步证实抑制TNFRSF10B的泛素化可能是GC转移的有希望的治疗策略。
    OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function.
    METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis.
    RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma.
    CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.
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