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sCD36 as a Biomarker for Progression and Recurrence in Type 2 Diabetes Mellitus Associated Hepatocellular Carcinoma. sCD36作为2型糖尿病相关肝细胞癌进展和复发的生物标志物
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-14 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S565006
Weiwei Dai, Fan Yang, Furao Guo, Yuling Ding, Deying He, Jiajia Zhang, Ying Guo, Yingying Gao, Anhua Xiao

Background: To evaluate the relationship between soluble CD36 (sCD36) and type 2 diabetes mellitus complicated by hepatocellular carcinoma (T2DM-HCC), and to explore its potential clinical prognostic value.

Methods: A prospective study was conducted enrolling newly diagnosed T2DM-HCC patients from two medical centers, along with control groups including healthy individuals (HC), T2DM patients, and HCC patients. Clinical, biochemical, and pathological data were collected. Serum sCD36 levels were measured by ELISA. Univariate and multivariate analyses were used to identify recurrence risk factors, and ROC analysis was performed to evaluate diagnostic performance.

Results: Among 258 participants, the T2DM-HCC group exhibited the highest sCD36 levels, impaired liver function, lower platelets, and mild chronic inflammation. In this group, sCD36 levels positively correlated with tumor stage, size, and proliferation. In univariable analysis, it was associated with postoperative recurrence (OR = 2.57, 95% CI: 0.68-9.67). The predictive ability of sCD36 for recurrence (AUC = 0.86) was comparable to AFP (AUC = 0.89), while their combination showed the highest accuracy (AUC = 0.94).

Conclusion: sCD36 is associated with tumor progression in T2DM-HCC patients and serves as an independent risk factor for recurrence. To the best of our knowledge, this is the first study to identify sCD36 as a critical clinical biomarker for disease progression in T2DM-HCC, with strong potential for clinical application.

Trial registration: This study was registered in September 2024 with the Chinese Clinical Trial Registry (ChiCTR), registration number: ChiCTR2400089651.

背景:探讨可溶性CD36 (sCD36)与2型糖尿病合并肝细胞癌(T2DM-HCC)的关系,并探讨其潜在的临床预后价值。方法:一项前瞻性研究纳入了来自两个医疗中心的新诊断的T2DM-HCC患者,以及包括健康人(HC)、T2DM患者和HCC患者在内的对照组。收集临床、生化及病理资料。ELISA法检测血清sCD36水平。采用单因素和多因素分析确定复发危险因素,采用ROC分析评价诊断效果。结果:258名参与者中,T2DM-HCC组sCD36水平最高,肝功能受损,血小板降低,轻度慢性炎症。在该组中,sCD36水平与肿瘤分期、大小和增殖呈正相关。在单变量分析中,它与术后复发相关(OR = 2.57, 95% CI: 0.68-9.67)。sCD36对复发的预测能力(AUC = 0.86)与AFP (AUC = 0.89)相当,两者联合预测准确率最高(AUC = 0.94)。结论:sCD36与T2DM-HCC患者的肿瘤进展相关,是复发的独立危险因素。据我们所知,这是第一个确定sCD36作为T2DM-HCC疾病进展的关键临床生物标志物的研究,具有很强的临床应用潜力。试验注册:本研究于2024年9月在中国临床试验注册中心(ChiCTR)注册,注册号:ChiCTR2400089651。
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引用次数: 0
Clinical Implications and Novel Insights into Adolescent Primary Liver Cancer: A Nightmare for Adolescents? 青少年原发性肝癌的临床意义和新见解:青少年的噩梦?
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-07 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S538084
Huidong Guo, Xiaojun Chen, Rong Li, Jianzhen Shen, Donghui Gan, Yue Yin, Hehui Zhang, Jiachen Xie, Longfei Xie, Yanquan Liu

Objective: This study retrospectively analyzed clinical data from adolescent primary liver cancer (PLC) cases over the past decade, summarizing clinical characteristics, diagnostic approaches, and prognostic outcomes to provide guidance for prevention, early diagnosis, and timely treatment of adolescent PLC.

Methods: Clinical data of 497 cases of adolescent PLC patients were collected from January 1, 2014, to December 31, 2024. The baseline demographic data, general condition, imaging, laboratory findings, and pathological features of these patients were described, and the diagnostic and therapeutic processes were analyzed, univariate and multivariate Cox regression analyses were conducted to identify significant prognostic factors.

Results: The age of onset for patients was 13.75 (10.25-19.00) years, with 311 males (62.58%) and 186 females (37.42%), yielding a male-to-female ratio of 1.67:1. Elevated ALT and GGT levels were observed in most patients, while all patients exhibited elevated ChE. Among all patients included in this study, 320 cases (64.39%) were infected with HBV, 469 cases (94.36%) were diagnosed with hepatocellular carcinoma (HCC), 14 cases (2.82%) with intrahepatic cholangiocarcinoma, and 14 cases (2.82%) with mixed hepatocellular-intrahepatic cholangiocarcinoma. The follow-up results showed the 1-year, 2-year, and 3-year survival rates in adolescent PLC patients were 45.27%, 20.32%, and 8.45%, respectively. The univariate Cox regression analysis revealed that adolescent PLC patients who accompanied with portal vein tumor thrombus, ascites, advanced CNLC stage, abnormalities in AFP, ALT, AST, AST/ALT ratio, GGT, ALP and TBIL, high ECOG score and non-surgical treatment had shorter OS (P < 0.05). Multivariate Cox regression analysis showed that portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing the OS of adolescent PLC patients (P < 0.05).

Conclusion: Clinical manifestations and symptoms of adolescent PLC patients lack specificity, and portal vein tumor thrombus, advanced CNLC stage, abnormalities in AFP, GGT, and non-surgical treatment were independent prognostic factors influencing OS in adolescent PLC.

目的:回顾性分析近十年来青少年原发性肝癌(PLC)病例的临床资料,总结其临床特点、诊断方法及预后,为青少年原发性肝癌的预防、早期诊断和及时治疗提供指导。方法:收集2014年1月1日至2024年12月31日497例青少年PLC患者的临床资料。描述这些患者的基线人口统计学资料、一般情况、影像学、实验室检查和病理特征,分析诊断和治疗过程,进行单因素和多因素Cox回归分析,以确定重要的预后因素。结果:患者发病年龄为13.75(10.25 ~ 19.00)岁,其中男性311例(62.58%),女性186例(37.42%),男女比例为1.67:1。大多数患者ALT和GGT水平升高,而所有患者均表现为ChE升高。本研究纳入的所有患者中,320例(64.39%)感染HBV, 469例(94.36%)诊断为肝细胞癌,14例(2.82%)诊断为肝内胆管癌,14例(2.82%)诊断为肝细胞-肝内胆管癌。随访结果显示,青少年PLC患者1年、2年、3年生存率分别为45.27%、20.32%、8.45%。单因素Cox回归分析显示,合并门静脉肿瘤血栓、腹水、CNLC晚期、AFP、ALT、AST、AST/ALT、GGT、ALP、TBIL异常、ECOG评分高且非手术治疗的青少年PLC患者生存期较短(P < 0.05)。多因素Cox回归分析显示,门静脉肿瘤血栓、CNLC晚期、AFP、GGT异常、非手术治疗是影响青少年PLC患者OS的独立预后因素(P < 0.05)。结论:青少年PLC患者的临床表现和症状缺乏特异性,门静脉肿瘤血栓、CNLC晚期、AFP、GGT异常及非手术治疗是影响青少年PLC OS的独立预后因素。
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引用次数: 0
Low Aggregate Index of Systemic Inflammation Values Correlate with Favorable Prognosis and High Abundance of Parabacteroides in Hepatocellular Carcinoma. 在肝细胞癌中,全身性炎症综合指数低与预后良好和副芽孢杆菌高丰度相关。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-06 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S538192
Wenju Sun, Fengqin Zhou, Chengyu Shi, Congcong Xu, Zhihai Wang, Xufeng Guo

Purpose: Systemic inflammatory response is reported to occupy a crucial role in the progression of hepatocellular carcinoma (HCC). The prognostic significance of SII and PNI in HCC has been explored, but the prognostic significance of aggregate index of systemic inflammation (AISI) in HCC is still unknown. This study was designed to determine the prognostic significance of AISI in HCC and explain the potential underlying mechanisms via gut microbiota and fecal metabolomic profiling.

Patients and methods: A cohort of 109 cases of HCC individuals during January 2023 to August 2024 was included into this clinical research, and the clinical information and fresh fecal samples were collected. The fecal samples were collected for 16S rRNA sequence and metabolomics analysis.

Results: Survival analysis revealed that HCC patients in low AISI group tend to experience relatively longer survival time compared with those in high AISI group. Then, we employed ROC analysis to measure the predictive performance of AISI for the survival outcome, and ROC curve showed that levels of AISI had good predictive performance for the survival status with an AUC of 0.771 (95%CI: 0.671-0.871). 16S rRNA sequencing results revealed that levels of Parabacteroides were up-regulated in the low AISI group, and levels of Fusicatenibacter were up-regulated in the high AISI group. Metabolic analysis demonstrated that cavipetin A, pemptoporphyrin, and 8-Oxo-dGMP with high VIP value were the most distinct fecal metabolites.

Conclusion: AISI is a potential prognostic biomarker in individuals with HCC. A low level of AISI was correlated with high abundance of Parabacteroides and some metabolites, indicating that AISI might affect the prognosis of HCC individuals via the regulations of gut microbes and metabolites.

目的:据报道,全身炎症反应在肝细胞癌(HCC)的进展中起着至关重要的作用。SII和PNI在HCC中的预后意义已被探讨,但系统性炎症总指数(AISI)在HCC中的预后意义尚不清楚。本研究旨在确定AISI在HCC中的预后意义,并通过肠道微生物群和粪便代谢组学分析解释潜在的潜在机制。患者与方法:选取2023年1月至2024年8月期间109例HCC患者作为临床研究对象,收集临床资料及新鲜粪便样本。采集粪便样本进行16S rRNA测序和代谢组学分析。结果:生存分析显示,与高AISI组相比,低AISI组HCC患者的生存时间相对较长。然后,我们采用ROC分析测量AISI水平对生存结局的预测性能,ROC曲线显示AISI水平对生存状态有较好的预测性能,AUC为0.771 (95%CI: 0.671-0.871)。16S rRNA测序结果显示,低AISI组Parabacteroides水平上调,高AISI组Fusicatenibacter水平上调。代谢分析表明,高VIP值的cavipetin A、pemptoporphyrin和8-Oxo-dGMP是最明显的粪便代谢产物。结论:AISI是HCC患者潜在的预后生物标志物。低水平的AISI与高丰度的拟副杆菌及部分代谢物相关,提示AISI可能通过调节肠道微生物及代谢物影响HCC患者预后。
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引用次数: 0
Risk Factors for Recurrence in Patients with Hepatocellular Carcinoma After Curative Resection or Ablation. 肝癌根治性切除或消融后复发的危险因素。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-06 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S552316
Fanzheng Meng, Jizhou Wang, Xiao-Dong Zhu, Meng Zhang, Xiaowu Zhang, Dantong Cheng, Xijie Zhang, Lianxin Liu

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a high incidence in China, largely due to the high prevalence of hepatitis B virus (HBV) infection. HBV‑related HCC often presents with aggressive characteristics but preserved liver function. Resection and ablation are approaches to achieve potentially curative outcomes. However, the recurrence rate is high, with up to 70% within five years. Curative surgery or ablation is used more broadly in China than in Western countries, so identifying patients at high risk of recurrence is essential: risk stratification can inform postoperative management, including surveillance intensity and avoidance of over- or under-treatment. Baseline characteristics provide a simple method of prediction, the impacts of which differ in early and late recurrence. To our knowledge, this is the first narrative review to comprehensively understand the identification, prevalence, and impact of risk factors for both early and late HCC recurrence in Chinese patients following curative‑intent resection or ablation. The review suggests that the most impactful risk factors for early recurrence are aggressive tumor features including tumor size, number and vascular invasion. For late recurrence, key risk factors are patient characteristics such as sex, viral infections and liver cirrhosis. As these risk factors are interrelated, several integrated predictive models like nomograms and artificial intelligence (AI) applications have been proposed, which may enhance risk stratification and inform personalized management strategies. These models should be further validated in large prospective studies to achieve clinical application.

肝细胞癌(HCC)是最常见的肝癌,在中国发病率很高,主要是由于乙型肝炎病毒(HBV)感染的高流行率。HBV相关的HCC通常表现为侵袭性特征,但保留了肝功能。切除和消融是达到潜在治愈效果的方法。然而,复发率高,5年内复发率高达70%。在中国,治疗性手术或消融的应用比西方国家更广泛,因此识别复发风险高的患者至关重要:风险分层可以为术后管理提供信息,包括监测强度和避免治疗过度或治疗不足。基线特征提供了一种简单的预测方法,其影响在早期和晚期复发中有所不同。据我们所知,这是第一个全面了解中国患者在治疗目的切除或消融后早期和晚期HCC复发的识别、患病率和危险因素影响的叙述性综述。综述表明,早期复发最重要的危险因素是肿瘤的侵袭性特征,包括肿瘤的大小、数量和血管侵犯。对于晚期复发,关键的危险因素是患者的特征,如性别、病毒感染和肝硬化。由于这些风险因素是相互关联的,因此提出了几种综合预测模型,如nomogram和人工智能(AI)应用,这些模型可以增强风险分层并为个性化管理策略提供信息。这些模型需要在大型前瞻性研究中进一步验证,以实现临床应用。
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引用次数: 0
ANT Score Nomogram for Predicting Very Early Recurrence of Hepatocellular Carcinoma. 预测肝细胞癌早期复发的ANT评分Nomogram。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-05 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S556733
Zichen Yu, Hanyu Wang, Qiang Huo, Wenli Cao, Liming Jin, Jie Liu, Fangqiang Wei

Background: Very early recurrence (VER), defined as recurrence within one year after curative resection of hepatocellular carcinoma (HCC), significantly impacts long-term survival. This study aimed to develop and validate the ANT Score, a novel prognostic model integrating nutrition, inflammation, and tumor burden to refine VER prediction.

Methods: A retrospective cohort of HCC patients undergoing curative liver resection was analyzed. Key predictors were identified using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, forming the ANT Score. Model performance was evaluated through receiver operating characteristic (ROC) curve analysis, DeLong's test, calibration curves, and decision curve analysis (DCA). The prognostic value of capsule integrity was also assessed.

Results: Among 459 included patients, 118 (25.7%) experienced VER. Patients were randomly assigned to training (70%) and test (30%) cohorts. The ANT Score, comprising albumin-to-alkaline phosphatase ratio (AAPR), neutrophil-to-albumin ratio (NPAR), and tumor burden score (TBS), demonstrated superior predictive performance (area under the curve [AUC] = 0.751, 95% confidence interval: 0.669-0.832, P < 0.05) compared to conventional markers. Capsule incompleteness was an independent risk factor but did not significantly enhance predictive accuracy (AUC = 0.76 vs 0.751, P > 0.05, DeLong test). The ANT Score-based nomogram exhibited excellent calibration and clinical utility in DCA.

Conclusion: The ANT Score is an independent and superior predictor of VER after curative HCC resection. The ANT Score-based nomogram showed promising predictive value, offering a practical tool for individualized risk assessment. External validation and prospective studies are warranted to further assess its clinical applicability.

背景:非常早期复发(VER),定义为肝细胞癌(HCC)根治性切除后一年内的复发,显著影响长期生存。本研究旨在开发和验证ANT评分,这是一种整合营养、炎症和肿瘤负担的新型预后模型,以完善VER预测。方法:对行根治性肝切除术的HCC患者进行回顾性队列分析。使用最小绝对收缩和选择算子(LASSO)回归和多元逻辑回归确定关键预测因子,形成ANT评分。通过受试者工作特征(ROC)曲线分析、德龙检验、校正曲线和决策曲线分析(DCA)评价模型的性能。还评估了胶囊完整性的预后价值。结果:459例患者中,有118例(25.7%)发生VER。患者被随机分配到训练组(70%)和测试组(30%)。由白蛋白与碱性磷酸酶比值(AAPR)、中性粒细胞与白蛋白比值(NPAR)和肿瘤负荷评分(TBS)组成的ANT评分与常规标记物相比,显示出更优越的预测性能(曲线下面积[AUC] = 0.751, 95%可信区间:0.669-0.832,P < 0.05)。胶囊不完整是独立的危险因素,但没有显著提高预测准确性(AUC = 0.76 vs 0.751, P < 0.05, DeLong检验)。基于ANT评分的图在DCA中表现出良好的校准和临床应用。结论:ANT评分是肝癌根治性切除术后VER的独立且优越的预测指标。基于ANT评分的nomogram显示了良好的预测价值,为个体化风险评估提供了实用的工具。需要外部验证和前瞻性研究来进一步评估其临床适用性。
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引用次数: 0
Predictive Value of Hepatic Steatosis for Postoperative Recurrence in Hepatitis B-Related Hepatocellular Carcinoma: Development of a Machine Learning-Based Prognostic Model. 肝脂肪变性对乙型肝炎相关肝细胞癌术后复发的预测价值:基于机器学习的预后模型的发展
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-11-01 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S536629
Aoyun Hao, Changlei Li, Ruitao Sun, Bin Tan, Guanming Shao, Kun Li, Na Li, Weiyu Hu, Chao Qu, Jingyu Cao

Background: With the increasing prevalence of obesity and type 2 diabetes, the number of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) coexisting with hepatic steatosis is steadily rising. However, the impact of hepatic steatosis on tumor recurrence following radical resection remains unclear.

Methods: We retrospectively analyzed a cohort of 733 HBV-infected patients diagnosed with HCC who underwent curative liver resection. Propensity score matching (PSM) was performed at a 1:2 ratio using 12 covariates to reduce selection bias and explore the association between preoperative hepatic steatosis and recurrence-free survival (RFS). Furthermore, we constructed a postoperative recurrence prediction model based on hepatic steatosis and other clinicopathological factors using 101 combinations of machine learning algorithms. The optimal model was identified through comprehensive evaluation and validation.

Results: After PSM, survival analysis revealed that patients without hepatic steatosis had significantly better RFS compared to those with steatosis. Multivariate Cox regression analysis confirmed that preoperative hepatic steatosis was an independent risk factor for recurrence following radical resection ( P = 0.006, HR:1.564, 95% CI:1.137-2.150). A recurrence prediction model was developed using hepatic steatosis and additional clinicopathological features through machine learning. Among the 101 models tested, the Random Survival Forest (RSF) model exhibited the best predictive performance, achieving a C-index of 0.719 in the training cohort. The model demonstrated high predictive accuracy for 1-, 2-, and 3-year recurrence, with AUC of 0.782, 0.856, and 0.898, respectively. Compared to conventional staging systems such as BCLC and CNLC, our model achieved superior performance, and decision curve analysis (DCA) demonstrated favorable clinical utility.

Conclusion: Preoperative hepatic steatosis is an independent predictor of recurrence after radical resection in patients with HBV-related HCC. The RSF-based machine learning model incorporating hepatic steatosis and other clinicopathological factors effectively predicts postoperative recurrence risk and may facilitate personalized clinical decision-making in this patient population.

背景:随着肥胖和2型糖尿病患病率的增加,乙型肝炎病毒(HBV)相关肝细胞癌(HCC)合并肝脂肪变性的患者数量稳步上升。然而,肝脂肪变性对根治性切除后肿瘤复发的影响尚不清楚。方法:我们回顾性分析了733例诊断为HCC并行根治性肝切除术的hbv感染患者。采用12个协变量,以1:2的比例进行倾向评分匹配(PSM),以减少选择偏倚,并探讨术前肝脂肪变性与无复发生存率(RFS)之间的关系。此外,我们使用101种机器学习算法组合构建了基于肝脂肪变性和其他临床病理因素的术后复发预测模型。通过综合评价和验证,确定了最优模型。结果:PSM后,生存分析显示无肝脂肪变性患者的RFS明显优于肝脂肪变性患者。多因素Cox回归分析证实术前肝脂肪变性是根治术后复发的独立危险因素(P = 0.006, HR:1.564, 95% CI:1.137 ~ 2.150)。通过机器学习,利用肝脂肪变性和其他临床病理特征建立了复发预测模型。在101个被测试的模型中,随机生存森林(RSF)模型的预测性能最好,在训练队列中的c指数为0.719。该模型对1年、2年和3年复发的预测精度较高,AUC分别为0.782、0.856和0.898。与传统的分期系统(如BCLC和CNLC)相比,我们的模型取得了更好的性能,决策曲线分析(DCA)显示了良好的临床实用性。结论:术前肝脂肪变性是hbv相关HCC根治术后复发的独立预测因子。结合肝脂肪变性和其他临床病理因素的基于rsf的机器学习模型可有效预测术后复发风险,并可促进该患者群体的个性化临床决策。
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引用次数: 0
The Role of Nuclear Medicine in Predicting Treatment Response to Immunotherapy and Targeted Therapy in Hepatocellular Carcinoma: A Narrative Review. 核医学在预测肝细胞癌免疫治疗和靶向治疗反应中的作用:综述。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-10-31 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S544565
Haibin Tu, Dingluan Lin, Cailong Chen

Objective: Targeted and immunotherapy offer new treatment options for patients with advanced hepatocellular carcinoma (HCC); however, the proportion of patients who benefit from these therapies remains limited. Moreover, these treatments can involve complications and add financial burdens to patients, underscoring the need to identify those who are likely to benefit. As an advanced molecular imaging technique, nuclear medicine has the potential to predict treatment efficacy in targeted and immunotherapy, though its predictive accuracy remains uncertain. This narrative review aims to summarize existing research on nuclear medicine applications in this area, providing clinicians with new perspectives.

Materials and methods: We conducted a literature review across multiple medical databases, including PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Relevant studies were identified, organized, and summarized to present findings in the field.

Results: The findings indicate that metrics such as maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) correlate with the efficacy of targeted and immunotherapy. Additionally, emerging nuclear medicine techniques have shown promise in predicting PD-L1 expression.

Conclusion: Nuclear medicine holds potential for identifying patients who are likely to benefit from targeted and immunotherapy. However, further refinements are necessary to optimize its predictive capabilities.

目的:靶向和免疫治疗为晚期肝细胞癌(HCC)患者提供新的治疗选择;然而,从这些疗法中受益的患者比例仍然有限。此外,这些治疗可能涉及并发症并增加患者的经济负担,因此需要确定哪些人可能受益。核医学作为一种先进的分子成像技术,具有预测靶向治疗和免疫治疗疗效的潜力,但其预测准确性尚不确定。本文旨在对核医学在这一领域的应用进行综述,为临床医生提供新的视角。材料和方法:我们对多个医学数据库进行了文献综述,包括PubMed、Embase、Cochrane Library、Web of Science和Scopus。相关研究被确定、组织和总结,以呈现该领域的发现。结果:研究结果表明,最大标准化摄取值(SUVmax)和代谢肿瘤体积(MTV)等指标与靶向治疗和免疫治疗的疗效相关。此外,新兴的核医学技术在预测PD-L1表达方面显示出了希望。结论:核医学在识别可能受益于靶向和免疫治疗的患者方面具有潜力。然而,需要进一步改进以优化其预测能力。
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引用次数: 0
Cms1 Ribosomal Small Subunit Homolog Promotes HCC Proliferation and Migration by Modulating the TNF/NF-κB Signaling Pathway. Cms1核糖体小亚基同源物通过调节TNF/NF-κB信号通路促进HCC增殖和迁移。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-10-28 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S549003
Tuo Zhang, Yongping Huang, Sha Hu, Yongjie Yu, Fang Qin, Yu Zhang, Zeming Cai, Haitao Wang, Peng Zhang, Jing Dai

Purpose: The study aims to further classify hepatocellular carcinoma (HCC) based on proliferative capacity, identify hub genes associated with highly proliferative HCC, and investigate its regulatory roles in HCC.

Materials and methods: Bioinformatics analysis was employed to establish classification of HCC and further identify the hub gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, Western Blot assay and tumor xenograft assay were employed to detect the proliferation of HCC cells. Transwell assay and Western blot assay were employed to detect the migration of HCC cells. RNA sequencing analysis was employed to explore the signaling pathways activated by the gene and verify it through rescue experiments.

Results: We classified HCC into three more precise subtypes termed Prolifer-low, Prolifer-mid and Prolifer-high, and also found that Cms1 ribosomal small subunit homolog 1 (CMSS1) was a hub gene associated with stronger proliferative capacity subgroup of HCC. Functional studies revealed that CMSS1 overexpression significantly promoted the proliferation of HCC cells in vitro and in vivo. Additionally, CMSS1 could also promote the migration and epithelial-mesenchymal transition of HCC cells. Mechanistically, RNA sequencing analysis revealed that CMSS1 knockdown inhibited the tumor necrosis factor (TNF) and downstream nuclear factor kappa B (NF-κB) signaling pathways. More importantly, TNF or NF-κB suppression could reverse the promoting effects of CMSS1 on HCC cells proliferation and migration.

Conclusion: The study suggested that CMSS1 could be a critical modulator of HCC tumorigenesis and metastasis through the TNF/NF-κB signaling pathway, thus being considered as a potential therapeutic target for HCC. Targeting CMSS1 may offer a novel strategy to inhibit NF-κB-driven inflammatory signaling and suppress tumor progression in HCC.

目的:本研究旨在进一步根据增殖能力对肝细胞癌(HCC)进行分类,鉴定与高增殖性HCC相关的枢纽基因,探讨其在HCC中的调控作用。材料与方法:采用生物信息学分析方法建立HCC的分类,进一步鉴定中心基因。采用细胞计数试剂盒-8 (CCK-8)法、集落形成法、Western Blot法和肿瘤异种移植法检测肝癌细胞的增殖情况。采用Transwell法和Western blot法检测肝癌细胞的迁移情况。通过RNA测序分析,探索该基因激活的信号通路,并通过抢救实验进行验证。结果:我们将HCC精确地分为低增殖体、中增殖体和高增殖体三种亚型,并发现Cms1核糖体小亚单位同源物1 (CMSS1)是与HCC增殖能力强亚群相关的枢纽基因。功能研究显示,CMSS1过表达可显著促进体外和体内肝癌细胞的增殖。此外,CMSS1还能促进HCC细胞的迁移和上皮间质转化。机制上,RNA测序分析显示,CMSS1敲低抑制肿瘤坏死因子(TNF)和下游核因子κB (NF-κB)信号通路。更重要的是,TNF或NF-κB抑制可逆转CMSS1对HCC细胞增殖和迁移的促进作用。结论:本研究提示CMSS1可能通过TNF/NF-κB信号通路成为HCC发生转移的重要调节因子,被认为是HCC潜在的治疗靶点。靶向CMSS1可能提供一种新的策略来抑制NF-κ b驱动的炎症信号并抑制HCC的肿瘤进展。
{"title":"Cms1 Ribosomal Small Subunit Homolog Promotes HCC Proliferation and Migration by Modulating the TNF/NF-κB Signaling Pathway.","authors":"Tuo Zhang, Yongping Huang, Sha Hu, Yongjie Yu, Fang Qin, Yu Zhang, Zeming Cai, Haitao Wang, Peng Zhang, Jing Dai","doi":"10.2147/JHC.S549003","DOIUrl":"10.2147/JHC.S549003","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to further classify hepatocellular carcinoma (HCC) based on proliferative capacity, identify hub genes associated with highly proliferative HCC, and investigate its regulatory roles in HCC.</p><p><strong>Materials and methods: </strong>Bioinformatics analysis was employed to establish classification of HCC and further identify the hub gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, Western Blot assay and tumor xenograft assay were employed to detect the proliferation of HCC cells. Transwell assay and Western blot assay were employed to detect the migration of HCC cells. RNA sequencing analysis was employed to explore the signaling pathways activated by the gene and verify it through rescue experiments.</p><p><strong>Results: </strong>We classified HCC into three more precise subtypes termed Prolifer-low, Prolifer-mid and Prolifer-high, and also found that Cms1 ribosomal small subunit homolog 1 (CMSS1) was a hub gene associated with stronger proliferative capacity subgroup of HCC. Functional studies revealed that CMSS1 overexpression significantly promoted the proliferation of HCC cells in vitro and in vivo. Additionally, CMSS1 could also promote the migration and epithelial-mesenchymal transition of HCC cells. Mechanistically, RNA sequencing analysis revealed that CMSS1 knockdown inhibited the tumor necrosis factor (TNF) and downstream nuclear factor kappa B (NF-κB) signaling pathways. More importantly, TNF or NF-κB suppression could reverse the promoting effects of CMSS1 on HCC cells proliferation and migration.</p><p><strong>Conclusion: </strong>The study suggested that CMSS1 could be a critical modulator of HCC tumorigenesis and metastasis through the TNF/NF-κB signaling pathway, thus being considered as a potential therapeutic target for HCC. Targeting CMSS1 may offer a novel strategy to inhibit NF-κB-driven inflammatory signaling and suppress tumor progression in HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 ","pages":"2429-2443"},"PeriodicalIF":3.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spontaneous Rupture of Hepatocellular Carcinoma: Pathogenesis, Clinical Management, Prognostic Factors, and Future Directions. 肝细胞癌自发性破裂:发病机制、临床管理、预后因素及未来发展方向。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S540510
Yuan Cheng, Feng Ye, Yongjun Chen

Spontaneous rupture of hepatocellular carcinoma (srHCC) is a life-threatening complication with complex pathophysiology and heterogeneous clinical presentations. This review aims to provide an up-to-date summary of the pathogenesis, clinical features, treatment strategies, prognostic factors, and emerging research in srHCC. We discuss current understanding of risk factors and rupture mechanisms, outline diagnostic and therapeutic approaches-including surgical, interventional, and systemic options-and explore postoperative management and prognosis. We also highlight recent clinical evidence and unmet research needs. Understanding the multifaceted nature of srHCC is essential to improve outcomes and guide future research directions.

肝细胞癌自发性破裂(srHCC)是一种危及生命的并发症,具有复杂的病理生理和异质性的临床表现。本文综述了srHCC的发病机制、临床特征、治疗策略、预后因素和最新研究进展。我们讨论了目前对危险因素和破裂机制的理解,概述了诊断和治疗方法,包括手术、介入和全身选择,并探讨了术后管理和预后。我们还强调了最近的临床证据和未满足的研究需求。了解srHCC的多面性对于改善预后和指导未来的研究方向至关重要。
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引用次数: 0
Postoperative Adjuvant Transcatheterarterial Chemoembolization Should Be Considered Selectively for Patients with Cytokeratin-19 Positive Hepatocellular Carcinoma. 细胞角蛋白-19阳性肝癌患者术后应选择性考虑经导管动脉化疗栓塞。
IF 3.4 3区 医学 Q2 ONCOLOGY Pub Date : 2025-10-27 eCollection Date: 2025-01-01 DOI: 10.2147/JHC.S537915
Rong-Yun Mai, Zheng Tao, Hong-Yang Huang, Can Zeng, Kai-Xiang Mo, Dan-Dan Zeng, Rong Liang, Yan Lin, Xiao-Bo Wang, Tao Bai, Le-Qun Li, Jia-Zhou Ye, Guo-Bin Wu

Background: This study aimed to evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) patients and to identify cases that may benefit from PA-TACE.

Methods: We conducted a retrospective analysis of 453 CK19+ HCC patients who underwent hepatectomy between November 2013 and June 2019 at our institution. We compared the recurrence-free survival (RFS) and overall survival (OS) between patients who received PA-TACE and those who did not, utilizing propensity score matching (PSM) to balance the groups.

Results: Before and after PSM, both RFS and OS were significantly greater in PA-TACE group compared to the non-TACE group. Multivariable analysis identified PA-TACE as a significantly favorable factor of RFS and OS. In subgroups analyses, PA-TACE significantly improved RFS and OS in patients with CK19+ HCC under the following conditions: alpha-fetoprotein ≥ 400 ng/mL, cirrhosis, tumor size ≥ 5 cm, multiple tumors, major resection, Edmondson-Steiner stage III-IV, macrovascular invasion and microvascular invasion. Similar results were obtained in patients with higher tumor stages. Further recurrence model analyses revealed that PA-TACE significantly reduced early recurrence in patients with high-risk of postoperative recurrence, but had little effect on late recurrence.

Conclusion: Among CK19+ HCC patients with higher recurrence of postoperative risk, PA-TACE could greatly improve RFS and OS.

背景:本研究旨在评估细胞角蛋白19阳性(CK19+)肝细胞癌(HCC)患者术后辅助经动脉化疗栓塞(PA-TACE)的临床疗效,并确定可能受益于PA-TACE的病例。方法:我们对2013年11月至2019年6月在我院接受肝切除术的453例CK19+ HCC患者进行了回顾性分析。我们比较了接受PA-TACE和未接受PA-TACE的患者的无复发生存期(RFS)和总生存期(OS),利用倾向评分匹配(PSM)来平衡组间的差异。结果:PSM前后,PA-TACE组RFS和OS均显著高于非tace组。多变量分析表明,PA-TACE是RFS和OS的显著有利因素。在亚组分析中,PA-TACE显著改善了以下条件下CK19+ HCC患者的RFS和OS:甲胎蛋白≥400 ng/mL、肝硬化、肿瘤大小≥5 cm、多发肿瘤、大切除、edmonson - steiner III-IV期、大血管和微血管侵袭。在肿瘤分期较高的患者中也获得了类似的结果。进一步的复发模型分析显示,PA-TACE可显著降低术后复发高危患者的早期复发,但对晚期复发影响不大。结论:在术后复发风险较高的CK19+ HCC患者中,PA-TACE可显著改善RFS和OS。
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引用次数: 0
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Journal of Hepatocellular Carcinoma
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