Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.2147/JHC.S484027
Dong Liu, Jianmin Wu, Han Wang, Hui Dong, Lei Chen, Ningyang Jia
Objective: To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored.
Methods: Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC's effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI's independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity.
Results: EC was an independent risk factor for MVI (p=0.038, OR=1.304 (95% CI: 1.014-1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737-0.836) vs AUC=0.748(95% CI: 0.694-0.802, p=0.005)). MVI was an independent risk factor for early recurrence (p<0.001, HR = 2.254 (95% CI: 1.557-3.263)). IS was negatively correlated with lymphocyte counts (R=-0.311, p=0.022), and positively correlated with EC (R=0.301, p=0.027) and RS (R = 0.315, p = 0.018).
Conclusion: EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.
{"title":"The Enhanced Role of Eosinophils in Radiomics-Based Diagnosis of Microvascular Invasion and Its Association with the Immune Microenvironment in Hepatocellular Carcinoma.","authors":"Dong Liu, Jianmin Wu, Han Wang, Hui Dong, Lei Chen, Ningyang Jia","doi":"10.2147/JHC.S484027","DOIUrl":"https://doi.org/10.2147/JHC.S484027","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored.</p><p><strong>Methods: </strong>Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC's effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI's independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity.</p><p><strong>Results: </strong>EC was an independent risk factor for MVI (<i>p</i>=0.038, OR=1.304 (95% CI: 1.014-1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737-0.836) vs AUC=0.748(95% CI: 0.694-0.802, <i>p</i>=0.005)). MVI was an independent risk factor for early recurrence (<i>p</i><0.001, HR = 2.254 (95% CI: 1.557-3.263)). IS was negatively correlated with lymphocyte counts (R=-0.311, <i>p</i>=0.022), and positively correlated with EC (R=0.301, <i>p</i>=0.027) and RS (R = 0.315, <i>p</i> = 0.018).</p><p><strong>Conclusion: </strong>EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1789-1800"},"PeriodicalIF":4.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348144","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}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.2147/JHC.S483861
Fangqian Du, Yuwei Xie, Shengze Wu, Mengling Ji, Bingzi Dong, Chengzhan Zhu
Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.
{"title":"Expression and Targeted Application of Claudins Family in Hepatobiliary and Pancreatic Diseases.","authors":"Fangqian Du, Yuwei Xie, Shengze Wu, Mengling Ji, Bingzi Dong, Chengzhan Zhu","doi":"10.2147/JHC.S483861","DOIUrl":"https://doi.org/10.2147/JHC.S483861","url":null,"abstract":"<p><p>Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1801-1821"},"PeriodicalIF":4.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348142","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}
Background: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.
Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.
Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.
Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.
{"title":"Impact of Duration of Adjuvant Therapy on Patients with Initially Unresectable Hepatocellular Carcinoma After Conversion Surgery: A Propensity Score Matching Study.","authors":"Zhong-Tai Lin, Shao-Ming Wei, Jun-Yi Wu, Zhi-Bo Zhang, Shuang-Jia Wang, Jian-Yin Zhou, Meng-Chao Luo, Zhen-Xin Zeng, Xiang-Ye Ou, Yang-Kai Fu, Han Li, De-Yi Liu, Jia-Yi Wu, Mao-Lin Yan","doi":"10.2147/JHC.S477019","DOIUrl":"https://doi.org/10.2147/JHC.S477019","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.</p><p><strong>Methods: </strong>This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.</p><p><strong>Results: </strong>No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.</p><p><strong>Conclusion: </strong>At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1777-1787"},"PeriodicalIF":4.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348143","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}
Xiaoju Huang, Mengmeng Wang, Dan Zhang, Junpeng Meng, Pian Liu
Background: Liver cancer is the sixth most common cancer worldwide, and hepatocellular carcinoma (HCC) presents one of the most challenging global health issues. ZDHHC20, a member of the ZDHHC palmitoyltransferase (ZDHHC-PAT) family, is involved in a reversible lipid modification known as palmitoylation, which contributes to the occurrence and progression of various tumors. However, the specific mechanisms underlying the involvement of ZDHHC20 in this process are unclear. Methods: The effects of both ZDHHC20 knockdown and overexpression on hepatocellular carcinoma cell proliferation were evaluated using PCR, Western blotting, CCK-8 assay, colony formation assay, cell cycle analysis, apoptosis analysis, and EDU assay. The TCGA-LIHC dataset was analyzed bioinformatically, and the phosphorylation level of PI3K and AKT in SK-Hep1 and Huh7 cells was assessed using Western blotting. Nude mouse subcutaneous xenograft experiments were conducted to evaluate the effects of different treatment conditions on mouse tumor growth. Results: ZDHHC20 knockdown inhibited cell proliferation and promoted apoptosis, while overexpression of ZDHHC20 promoted cell proliferation and inhibited apoptosis. Knockdown of ZDHHC20 also decreased phosphorylation of PI3K and AKT in HCC, whereas overexpression of ZDHHC20 increased phosphorylation of PI3K and AKT. The PI3K-AKT pathway inhibitors, LY294002 and MK2206, effectively inhibited the promotional effects of ZDHHC20 on the proliferation and growth of HCC. Conclusion: High expression of ZDHHC20 promotes the proliferation and tumor growth of HCC by activating the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 and the AKT inhibitor MK2206 inhibit the promotional effects of ZDHHC20 on the proliferation of HCC and the growth of tumors.
{"title":"ZDHHC20 Activates AKT Signaling Pathway to Promote Cell Proliferation in Hepatocellular Carcinoma","authors":"Xiaoju Huang, Mengmeng Wang, Dan Zhang, Junpeng Meng, Pian Liu","doi":"10.2147/jhc.s457682","DOIUrl":"https://doi.org/10.2147/jhc.s457682","url":null,"abstract":"<strong>Background:</strong> Liver cancer is the sixth most common cancer worldwide, and hepatocellular carcinoma (HCC) presents one of the most challenging global health issues. ZDHHC20, a member of the ZDHHC palmitoyltransferase (ZDHHC-PAT) family, is involved in a reversible lipid modification known as palmitoylation, which contributes to the occurrence and progression of various tumors. However, the specific mechanisms underlying the involvement of ZDHHC20 in this process are unclear.<br/><strong>Methods:</strong> The effects of both ZDHHC20 knockdown and overexpression on hepatocellular carcinoma cell proliferation were evaluated using PCR, Western blotting, CCK-8 assay, colony formation assay, cell cycle analysis, apoptosis analysis, and EDU assay. The TCGA-LIHC dataset was analyzed bioinformatically, and the phosphorylation level of PI3K and AKT in SK-Hep1 and Huh7 cells was assessed using Western blotting. Nude mouse subcutaneous xenograft experiments were conducted to evaluate the effects of different treatment conditions on mouse tumor growth.<br/><strong>Results:</strong> ZDHHC20 knockdown inhibited cell proliferation and promoted apoptosis, while overexpression of ZDHHC20 promoted cell proliferation and inhibited apoptosis. Knockdown of ZDHHC20 also decreased phosphorylation of PI3K and AKT in HCC, whereas overexpression of ZDHHC20 increased phosphorylation of PI3K and AKT. The PI3K-AKT pathway inhibitors, LY294002 and MK2206, effectively inhibited the promotional effects of ZDHHC20 on the proliferation and growth of HCC.<br/><strong>Conclusion:</strong> High expression of ZDHHC20 promotes the proliferation and tumor growth of HCC by activating the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 and the AKT inhibitor MK2206 inhibit the promotional effects of ZDHHC20 on the proliferation of HCC and the growth of tumors.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"39 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to identify dendritic cells (DCs) related genes in hepatocellular carcinoma (HCC) patients, establish DC-related subtypes and signatures, and correlate them with prognosis and treatment response. Methods: DC-related genes were screened using Weighted Gene Co-expression Network Analysis (WGCNA) based on RNA sequencing from the TCGA (374 samples), GSE14520 (242 samples), and GSE76427 datasets (115 samples), following immune infiltration assessment by the TIME method. Two DC-related subtypes in HCC were identified through unsupervised clustering. A DC-related signature (DCRS) predictive of overall survival was constructed using LASSO and Cox regression models, and validated across the three datasets. Additionally, genetic mutation characteristics, immune infiltration levels, and treatment sensitivity were explored in DCRS risk groups. The expression levels of DCRS genes and risk scores were validated in the transcriptome of 13 HCC patients receiving combined targeted therapy and immunotherapy in the Guangxi cohort using Wilcoxon test. Results: A signature consisting of 13 genes related to DCs was constructed, and the superior prognostic consistency of the low DCRS risk group was validated across the TCGA (P=0.003), GSE76427 (P=0.005), and GSE14520 (P=0.047) datasets. Furthermore, in the 147-sample transarterial chemoembolization (TACE) treatment dataset GSE104580, the response group exhibited lower risk scores than the non-response group (P=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (P=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (P=0.027), the risk scores were higher in the response group. We also validated the gene expression levels of DCRS and the higher risk scores in the response group of the Guangxi cohort (P=0.034). Conclusion: A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy.
背景：本研究旨在鉴定肝细胞癌（HCC）患者的树突状细胞（DCs）相关基因，建立DC相关亚型和特征，并将其与预后和治疗反应相关联：根据TCGA（374个样本）、GSE14520（242个样本）和GSE76427数据集（115个样本）中的RNA测序结果，采用加权基因共表达网络分析（WGCNA）筛选了DC相关基因，并采用TIME方法评估了免疫浸润情况。通过无监督聚类，确定了两种与 HCC 中 DC 相关的亚型。利用 LASSO 和 Cox 回归模型构建了可预测总生存期的 DC 相关特征（DCRS），并在三个数据集中进行了验证。此外，还探讨了DCRS风险组的基因突变特征、免疫浸润水平和治疗敏感性。在广西队列中接受联合靶向治疗和免疫治疗的13例HCC患者的转录组中，使用Wilcoxon检验验证了DCRS基因的表达水平和风险评分：结果：由13个与DCs相关的基因组成的特征被构建出来，低DCRS风险组的预后一致性在TCGA（P=0.003）、GSE76427（P=0.005）和GSE14520（P=0.047）数据集中得到了验证。此外，在147个样本的经动脉化疗栓塞（TACE）治疗数据集GSE104580中，应答组的风险评分低于非应答组（P=0.01），而在140个样本的索拉非尼治疗数据集GSE109211（P=0.041）和17个样本的抗PD-1治疗数据集GSE202069（P=0.027）中，应答组的风险评分更高。我们还验证了DCRS的基因表达水平和广西队列中应答组较高的风险评分（P=0.034）：结论：在HCC中建立了由13个基因组成的DCRS，有助于预测患者的预后以及对TACE、靶向治疗和免疫治疗的反应性。
{"title":"Dendritic Cell-Related Gene Signatures in Hepatocellular Carcinoma: An Analysis for Prognosis and Therapy Efficacy Evaluation","authors":"Huasheng Huang, Shayong Peng, Yongguang Wei, Chenlu Lan, Wei Qin, Xiwen Liao, Cheng-Kun Yang, Guangzhi Zhu, Xin Zhou, Tao Peng","doi":"10.2147/jhc.s481338","DOIUrl":"https://doi.org/10.2147/jhc.s481338","url":null,"abstract":"<strong>Background:</strong> This study aimed to identify dendritic cells (DCs) related genes in hepatocellular carcinoma (HCC) patients, establish DC-related subtypes and signatures, and correlate them with prognosis and treatment response.<br/><strong>Methods:</strong> DC-related genes were screened using Weighted Gene Co-expression Network Analysis (WGCNA) based on RNA sequencing from the TCGA (374 samples), GSE14520 (242 samples), and GSE76427 datasets (115 samples), following immune infiltration assessment by the TIME method. Two DC-related subtypes in HCC were identified through unsupervised clustering. A DC-related signature (DCRS) predictive of overall survival was constructed using LASSO and Cox regression models, and validated across the three datasets. Additionally, genetic mutation characteristics, immune infiltration levels, and treatment sensitivity were explored in DCRS risk groups. The expression levels of DCRS genes and risk scores were validated in the transcriptome of 13 HCC patients receiving combined targeted therapy and immunotherapy in the Guangxi cohort using Wilcoxon test.<br/><strong>Results:</strong> A signature consisting of 13 genes related to DCs was constructed, and the superior prognostic consistency of the low DCRS risk group was validated across the TCGA (<em>P</em>=0.003), GSE76427 (<em>P</em>=0.005), and GSE14520 (<em>P</em>=0.047) datasets. Furthermore, in the 147-sample transarterial chemoembolization (TACE) treatment dataset GSE104580, the response group exhibited lower risk scores than the non-response group (<em>P</em>=0.01), whereas in the 140-sample Sorafenib treatment dataset GSE109211 (<em>P</em>=0.041) and the 17-sample anti-PD-1 treatment dataset GSE202069 (<em>P</em>=0.027), the risk scores were higher in the response group. We also validated the gene expression levels of DCRS and the higher risk scores in the response group of the Guangxi cohort (<em>P</em>=0.034).<br/><strong>Conclusion:</strong> A DCRS consisting of 13 genes was established in HCC, facilitating the prediction of patient prognosis and responsiveness to TACE, targeted therapy, and immunotherapy. <br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Letter for the article An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization
致信《与氧化应激相关的预后特征可预测经动脉化疗栓塞术后肝细胞癌的治疗反应和疗效
{"title":"Predicting Treatment Response and Prognosis in Patients with Hepatocellular Carcinoma after Interventional Therapy [Letter]","authors":"Hang Li, Xiping Shen, Ji Wu","doi":"10.2147/jhc.s494470","DOIUrl":"https://doi.org/10.2147/jhc.s494470","url":null,"abstract":"Letter for the article An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<strong>Purpose:</strong> Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC.<br/><strong>Patients and Methods:</strong> A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score–matching (PSM).<br/><strong>Results:</strong> The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs).<br/><strong>Conclusion:</strong> Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.<br/><br/><strong>Plain Language Summary:</strong> Infiltrative hepatocellular carcinoma (HCC) is an odd group that is not well adjudicated in the current staging systems, and treatment options for patients with infiltrative HCC are challenging with scant and insufficient clinical evidence. In this multi-center study, we innovatively analyzed the outcome of hepatic arterial infusion chemotherapy (HAIC) combined lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1) was associated longer progression-free survival and overall survival than Lenvatinib plus PD-1 inhibitor combination (Len+PD-1) for patient with infiltrative HCC. In addition, further intragroup analysis revealed that OS of patients with and without metastasis in Len+PD-1 group was significant difference. However, no difference was observed in OS for patients with and without metastasis in HAIC+Len+PD-1 group. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. Our research provides evidence that HAIC combined Lenvatinib and PD-1 inhibitor results in clinically significant improvements in infiltrative HCC. It could be recommended as a first choice for infiltr
{"title":"Hepatic Arterial Infusion Chemotherapy Combined Lenvatinib and PD-1 Inhibitor Showed Improved Survival for Infiltrative Hepatocellular Carcinoma: A Multicenter Cohort Study","authors":"Ruixia Li, Xiaohui Wang, Hui Li, Murong Wang, Juncheng Wang, Wei Wang, Qunfang Zhou","doi":"10.2147/jhc.s477872","DOIUrl":"https://doi.org/10.2147/jhc.s477872","url":null,"abstract":"<strong>Purpose:</strong> Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC.<br/><strong>Patients and Methods:</strong> A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score–matching (PSM).<br/><strong>Results:</strong> The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs).<br/><strong>Conclusion:</strong> Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.<br/><br/><strong>Plain Language Summary:</strong> Infiltrative hepatocellular carcinoma (HCC) is an odd group that is not well adjudicated in the current staging systems, and treatment options for patients with infiltrative HCC are challenging with scant and insufficient clinical evidence. In this multi-center study, we innovatively analyzed the outcome of hepatic arterial infusion chemotherapy (HAIC) combined lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1) was associated longer progression-free survival and overall survival than Lenvatinib plus PD-1 inhibitor combination (Len+PD-1) for patient with infiltrative HCC. In addition, further intragroup analysis revealed that OS of patients with and without metastasis in Len+PD-1 group was significant difference. However, no difference was observed in OS for patients with and without metastasis in HAIC+Len+PD-1 group. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. Our research provides evidence that HAIC combined Lenvatinib and PD-1 inhibitor results in clinically significant improvements in infiltrative HCC. It could be recommended as a first choice for infiltr","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"33 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shanshan Chen, Youjia Duan, Yongchao Zhang, Long Cheng, Liang Cai, Xiaopu Hou, Xiaojun Wang, Wei Li
Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.
Keywords: thermal ablation, aspirin, hepatocellular carcinoma, survival analysis, retrospective study
{"title":"Effect of Low-Dose Aspirin Use After Thermal Ablation in Patients with Hepatocellular Carcinoma: A Retrospective Study","authors":"Shanshan Chen, Youjia Duan, Yongchao Zhang, Long Cheng, Liang Cai, Xiaopu Hou, Xiaojun Wang, Wei Li","doi":"10.2147/jhc.s435524","DOIUrl":"https://doi.org/10.2147/jhc.s435524","url":null,"abstract":"<strong>Purpose:</strong> To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation.<br/><strong>Methods:</strong> A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.<br/><strong>Results:</strong> A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (<em>P</em> = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (<em>P</em> = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups.<br/><strong>Conclusion:</strong> Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.<br/><br/><strong>Keywords:</strong> thermal ablation, aspirin, hepatocellular carcinoma, survival analysis, retrospective study<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"118 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Powell, Cristian Coarfa, Elisa Ruiz-Echartea, Sandra L Grimm, Omar Najjar, Bing Yu, Luis Olivares, Michael E Scheurer, Christie Ballantyne, Abeer Alsarraj, Emad Mohamed Salem, Aaron P Thrift, Hashem B El Serag, Salma Kaochar
Background: Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection. Methods: We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used machine learning models to identify a minimal panel to distinguish between cases and controls. Results: Among cases compared with controls, 124 metabolites and 246 lipids were upregulated, while 208 metabolites and 73 lipids were downregulated. The top upregulated metabolites were glycoursodeoxycholic acid, 5-methyltetrahydrofolic acid, octanoyl-coenzyme A, and glycocholic acid. Elevated lipids comprised glycerol lipids, cardiolipin, and phosphatidylethanolamine, whereas suppressed lipids included oxidized phosphatidylcholine and lysophospholipids. There was an overlap between differentially expressed metabolites and lipids and previously published transcriptomic signatures, illustrating an association with liver disease severity. A panel of 12 metabolites that distinguished between cases and controls with an area under the receiver operating curve of 0.98 for the support vector machine (interquartile range, 0.9– 1). Conclusion: Using prediagnostic serum samples, we identified a promising metabolites panel that accurately identifies patients with cirrhosis who progressed to HCC. Further validation of this panel is required.
背景：早期检测肝细胞癌（HCC）对改善患者预后至关重要，但我们缺乏可靠的临床生物标志物。本研究旨在确定用于早期检测 HCC 的代谢物和/或脂质面板：方法：我们开发了一种基于高分辨率液相色谱质谱（LC-MS）的分析平台，并评估了28份诊断前血清样本（来自随后发展为HCC的肝硬化患者（病例））与30份样本（来自无HCC的肝硬化患者（对照组））之间的全局代谢组和脂质组的差异。我们将差异表达的代谢物和脂质与公开数据集中的相关基因、蛋白质和转录组特征联系起来。我们使用机器学习模型确定了区分病例和对照组的最小面板：结果：与对照组相比，病例中有124种代谢物和246种脂类上调，208种代谢物和73种脂类下调。上调最多的代谢物是糖脱氧胆酸、5-甲基四氢叶酸、辛酰辅酶 A 和甘氨胆酸。升高的脂质包括甘油脂质、心磷脂和磷脂酰乙醇胺，而抑制的脂质包括氧化磷脂酰胆碱和溶血磷脂。差异表达的代谢物和脂质与之前发表的转录组特征有重叠，这说明它们与肝病的严重程度有关。支持向量机的接收器工作曲线下面积为 0.98（四分位间范围为 0.9-1），由此得出结论：12 种代谢物组成的小组能够区分病例和对照组：通过使用诊断前血清样本，我们发现了一个很有前景的代谢物面板，它能准确识别进展为 HCC 的肝硬化患者。我们还需要对这一面板进行进一步验证。
{"title":"Differences in Prediagnostic Serum Metabolomic and Lipidomic Profiles Between Cirrhosis Patients with and without Incident Hepatocellular Carcinoma","authors":"Hannah Powell, Cristian Coarfa, Elisa Ruiz-Echartea, Sandra L Grimm, Omar Najjar, Bing Yu, Luis Olivares, Michael E Scheurer, Christie Ballantyne, Abeer Alsarraj, Emad Mohamed Salem, Aaron P Thrift, Hashem B El Serag, Salma Kaochar","doi":"10.2147/jhc.s474010","DOIUrl":"https://doi.org/10.2147/jhc.s474010","url":null,"abstract":"<strong>Background:</strong> Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection.<br/><strong>Methods:</strong> We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used machine learning models to identify a minimal panel to distinguish between cases and controls.<br/><strong>Results:</strong> Among cases compared with controls, 124 metabolites and 246 lipids were upregulated, while 208 metabolites and 73 lipids were downregulated. The top upregulated metabolites were glycoursodeoxycholic acid, 5-methyltetrahydrofolic acid, octanoyl-coenzyme A, and glycocholic acid. Elevated lipids comprised glycerol lipids, cardiolipin, and phosphatidylethanolamine, whereas suppressed lipids included oxidized phosphatidylcholine and lysophospholipids. There was an overlap between differentially expressed metabolites and lipids and previously published transcriptomic signatures, illustrating an association with liver disease severity. A panel of 12 metabolites that distinguished between cases and controls with an area under the receiver operating curve of 0.98 for the support vector machine (interquartile range, 0.9– 1).<br/><strong>Conclusion:</strong> Using prediagnostic serum samples, we identified a promising metabolites panel that accurately identifies patients with cirrhosis who progressed to HCC. Further validation of this panel is required.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"19 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02eCollection Date: 2024-01-01DOI: 10.2147/JHC.S480082
Wei-Li Xia, Xiao-Hui Zhao, Yuan Guo, Hong-Tao Hu, Hai-Liang Li
Background and objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS.
Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.
Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02).
Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.
{"title":"TACE Combined with Portal Vein Tumor Thrombus <sup>125</sup>I Seed Implantation in the Treatment of HCC with Hepatic Arterioportal Shunts.","authors":"Wei-Li Xia, Xiao-Hui Zhao, Yuan Guo, Hong-Tao Hu, Hai-Liang Li","doi":"10.2147/JHC.S480082","DOIUrl":"10.2147/JHC.S480082","url":null,"abstract":"<p><strong>Background and objectives: </strong>Transarterial chemoembolization (TACE) and <sup>125</sup>I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and <sup>125</sup>I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT <sup>125</sup>I seed implantation in the treatment of HCC patients with APS.</p><p><strong>Methods: </strong>Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and <sup>125</sup>I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.</p><p><strong>Results: </strong>All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (<i>P</i>=0.02).</p><p><strong>Conclusion: </strong>For HCC patients with PVTT and APS, TACE combine with <sup>125</sup>I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1689-1697"},"PeriodicalIF":4.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154312","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}
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