Bo Jiang, Dong Lu, Jiaying Dai, Kunfeng Li, Qianqian Du, Bo Xie, Jun Xie, Xianhai Zhu, Xiang Xie
Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.
Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model
{"title":"A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE","authors":"Bo Jiang, Dong Lu, Jiaying Dai, Kunfeng Li, Qianqian Du, Bo Xie, Jun Xie, Xianhai Zhu, Xiang Xie","doi":"10.2147/jhc.s458657","DOIUrl":"https://doi.org/10.2147/jhc.s458657","url":null,"abstract":"<strong>Objective:</strong> To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).<br/><strong>Methods:</strong> Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems.<br/><strong>Results:</strong> The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems.<br/><strong>Conclusion:</strong> The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"332 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576861","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}
Yu-Kai Li, Song Wu, Yu-Shan Wu, Wei-Hu Zhang, Yan Wang, Yue-Hua Li, Qiang Kang, Song-Quan Huang, Kai Zheng, Gai-Ming Jiang, Qing-Bo Wang, Yu-Bo Liang, Jin Li, Yawhan Lakang, Chen Yang, Jing Li, Jia-Ping Wang, Xiang Kui, Yang Ke
Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.
背景:优势动脉供血是肝细胞癌(HCC)的一个特征。然而,血供能否预测肝癌患者肝切除术后的预后尚不清楚。这项回顾性研究调查了肝切除术后的 HCC 患者通过三相肝 CT 估测的门静脉和动脉血供(分别为门静脉系数 PVC 和肝动脉系数 HAC)的预后价值。方法:回顾性筛选2016年1月1日至2020年12月31日期间在昆明医科大学第二附属医院接受R0肝切除术的HCC患者,这些患者在肝切除术前2周接受了三相肝CT检测。采用最小绝对缩减和选择算子以及Cox比例危险回归模型,对他们的PVC和HAC以及其他变量进行分析,以预测总生存期(OS)和无复发生存期(RFS):共评估了 419 名患者(53.2 ± 10.6 岁,370 名男性)。较短的OS与较高的血白蛋白和总胆红素等级[危险比(HR)2.020,95%置信区间(CI)1.534- 2.660]、较高的巴塞罗那临床肝癌(BCLC)分期(HR 1.514,95% CI 1.290- 1.777)、PVC ≤ 0.386(HR 1.628,95% CI 1.149- 2.305)和HAC >0.029(HR 1.969,95% CI 1.380- 2.809)独立相关。RFS较短与男性(HR 1.652,95% CI 1.005- 2.716)、血清α-胎儿蛋白≥400 ng/mL(HR 1.672,95% CI 1.236- 2.HR1.641,95% CI 1.198- 2.249),肿瘤HAC> 0.029(HR 1.455,95% CI 1.060- 1.997):结论:肝切除术前的肿瘤PVC或HAC可独立预测HCC患者的术后生存率。
{"title":"Portal Venous and Hepatic Arterial Coefficients Predict Post-Hepatectomy Overall and Recurrence-Free Survival in Patients with Hepatocellular Carcinoma: A Retrospective Study","authors":"Yu-Kai Li, Song Wu, Yu-Shan Wu, Wei-Hu Zhang, Yan Wang, Yue-Hua Li, Qiang Kang, Song-Quan Huang, Kai Zheng, Gai-Ming Jiang, Qing-Bo Wang, Yu-Bo Liang, Jin Li, Yawhan Lakang, Chen Yang, Jing Li, Jia-Ping Wang, Xiang Kui, Yang Ke","doi":"10.2147/jhc.s462168","DOIUrl":"https://doi.org/10.2147/jhc.s462168","url":null,"abstract":"<strong>Background:</strong> The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.<br/><strong>Methods:</strong> HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.<br/><strong>Results:</strong> Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).<br/><strong>Conclusion:</strong> Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. <br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"2017 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576862","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: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME). Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system. Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1–derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration. Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.
{"title":"CD276 Promotes an Inhibitory Tumor Microenvironment in Hepatocellular Carcinoma and is Associated with Poor Prognosis","authors":"Wen-Feng Liu, Qiu-Yu Jiang, Zhuo-Ran Qi, Feng Zhang, Wen-Qing Tang, Hao-Qi Wang, Ling Dong","doi":"10.2147/jhc.s469529","DOIUrl":"https://doi.org/10.2147/jhc.s469529","url":null,"abstract":"<strong>Background:</strong> CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME).<br/><strong>Methods:</strong> The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system.<br/><strong>Results:</strong> CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8<sup>+</sup> T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1–derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration.<br/><strong>Conclusion:</strong> CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"4 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576864","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}
Purpose: The aim of our study was to investigate the relationship between albumin-bilirubin (ALBI) grade and recurrence in patients who underwent TACE sequential ablation. We developed and validated a nomogram to predict low levels of ALBI patients’ recurrence. Patients and Methods: A total of 880 patients undergoing TACE combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were retrospectively enrolled, including 415 patients with L-ALBI (≤-2.6) and 465 patients with high levels (>-2.6) of ALBI (H-ALBI). L-ALBI patients were randomized in a 7:3 ratio into the training cohort (N=289) and validation cohort (N=126). Multivariate Cox regression followed by random survival forest was carried out to identify independent risk factors for prediction nomogram construction. An examination of nomogram accuracy was performed using the C-index, receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) curves. According to the nomogram, the patients were divided into low-risk, intermediate-risk, and high-risk groups. Kaplan-Meier (KM) curves were applied to compare the difference in recurrence-free survival (RFS) among the three groups. Results: The median RFS in L-ALBI patients was significantly longer than the H-ALBI patients (40.8m vs 20.1m, HR:1.71, 95% CI:1.44– 2.04, P< 0.0001). The nomogram was composed of five variables, such as age, Barcelona Clinic Liver Cancer (BCLC) stage, globulin, gamma-glutamyl transferase to lymphocyte ratio (GLR), and international normalized ratio (INR). The C-index (0.722 and 0.731) and 1-, 3-, and 5-year AUCs (0.725, 0.803, 0.870, and 0.764, 0.816, 0.798) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves demonstrated good consistency and good clinical utility. There were significant differences in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001). Conclusion: L-ALBI Patients who underwent TACE combined ablation had better recurrence-free survival than patients with H-ALBI. The nomogram developed and validated in our study had good predictive ability in recurrence for L-ALBI patients.
{"title":"Recurrence of Hepatocellular Carcinoma in Patients with Low Albumin-Bilirubin Grade in TACE Combined with Ablation: A Random Forest Cox Predictive Model","authors":"Yiqi Xiong, Wenying Qiao, Tingting Mei, Kang Li, Ronghua Jin, Yonghong Zhang","doi":"10.2147/jhc.s465962","DOIUrl":"https://doi.org/10.2147/jhc.s465962","url":null,"abstract":"<strong>Purpose:</strong> The aim of our study was to investigate the relationship between albumin-bilirubin (ALBI) grade and recurrence in patients who underwent TACE sequential ablation. We developed and validated a nomogram to predict low levels of ALBI patients’ recurrence.<br/><strong>Patients and Methods:</strong> A total of 880 patients undergoing TACE combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were retrospectively enrolled, including 415 patients with L-ALBI (≤-2.6) and 465 patients with high levels (>-2.6) of ALBI (H-ALBI). L-ALBI patients were randomized in a 7:3 ratio into the training cohort (N=289) and validation cohort (N=126). Multivariate Cox regression followed by random survival forest was carried out to identify independent risk factors for prediction nomogram construction. An examination of nomogram accuracy was performed using the C-index, receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) curves. According to the nomogram, the patients were divided into low-risk, intermediate-risk, and high-risk groups. Kaplan-Meier (KM) curves were applied to compare the difference in recurrence-free survival (RFS) among the three groups.<br/><strong>Results:</strong> The median RFS in L-ALBI patients was significantly longer than the H-ALBI patients (40.8m vs 20.1m, HR:1.71, 95% CI:1.44– 2.04, P< 0.0001). The nomogram was composed of five variables, such as age, Barcelona Clinic Liver Cancer (BCLC) stage, globulin, gamma-glutamyl transferase to lymphocyte ratio (GLR), and international normalized ratio (INR). The C-index (0.722 and 0.731) and 1-, 3-, and 5-year AUCs (0.725, 0.803, 0.870, and 0.764, 0.816, 0.798) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves demonstrated good consistency and good clinical utility. There were significant differences in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).<br/><strong>Conclusion:</strong> L-ALBI Patients who underwent TACE combined ablation had better recurrence-free survival than patients with H-ALBI. The nomogram developed and validated in our study had good predictive ability in recurrence for L-ALBI patients.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, HCC, ablation, nomogram, recurrence, albumin-bilirubin, ALBI<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"29 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141576863","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: Posthepatectomy liver failure (PHLF) is a serious complication associated with high mortality rates. Machine learning (ML) has rapidly developed and may outperform traditional models in predicting PHLF in patients who have undergone hepatectomy. This study aimed to predict PHLF using ML and compare its performance with that of traditional scoring systems. Methods: The clinicopathological data of 334 patients who underwent liver resection were retrospectively collected. The Pycaret library, a simple, open-source machine learning library, was used to compare multiple classification models for PHLF prediction. The predictive performance of 15 ML algorithms was compared using the mean area under the receiver operating characteristic curve (AUROC) and accuracy, and the best-fit model was selected among 15 ML algorithms. Next, the predictive performance of the selected ML-PHLF model was compared with that of routine scoring systems, the albumin-bilirubin score (ALBI) and the fibrosis-4 (FIB-4) index, using AUROC. Results: The best model was extreme gradient boosting (accuracy:93.1%; AUROC:0.863) among the 15 ML algorithms. As compared with ALBI and FIB-4, the ML PHLF model had higher AUROC for predicting PHLF. Conclusion: The novel ML model for predicting PHLF outperformed routine scoring systems.
{"title":"Utility of Machine Learning in the Prediction of Post-Hepatectomy Liver Failure in Liver Cancer","authors":"Hirotaka Tashiro, Takashi Onoe, Naoki Tanimine, Sho Tazuma, Yoshiyuki Shibata, Takeshi Sudo, Haruki Sada, Norimitsu Shimada, Hirofumi Tazawa, Takahisa Suzuki, Yosuke Shimizu","doi":"10.2147/jhc.s451025","DOIUrl":"https://doi.org/10.2147/jhc.s451025","url":null,"abstract":"<strong>Background:</strong> Posthepatectomy liver failure (PHLF) is a serious complication associated with high mortality rates. Machine learning (ML) has rapidly developed and may outperform traditional models in predicting PHLF in patients who have undergone hepatectomy. This study aimed to predict PHLF using ML and compare its performance with that of traditional scoring systems.<br/><strong>Methods:</strong> The clinicopathological data of 334 patients who underwent liver resection were retrospectively collected. The Pycaret library, a simple, open-source machine learning library, was used to compare multiple classification models for PHLF prediction. The predictive performance of 15 ML algorithms was compared using the mean area under the receiver operating characteristic curve (AUROC) and accuracy, and the best-fit model was selected among 15 ML algorithms. Next, the predictive performance of the selected ML-PHLF model was compared with that of routine scoring systems, the albumin-bilirubin score (ALBI) and the fibrosis-4 (FIB-4) index, using AUROC.<br/><strong>Results:</strong> The best model was extreme gradient boosting (accuracy:93.1%; AUROC:0.863) among the 15 ML algorithms. As compared with ALBI and FIB-4, the ML PHLF model had higher AUROC for predicting PHLF.<br/><strong>Conclusion:</strong> The novel ML model for predicting PHLF outperformed routine scoring systems.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"2 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546418","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}
Purpose: The crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSCs) is one of the important mechanisms of liver cancer metastasis. The relationship between liver cancer metastasis and glycolysis has been extensively studied recently. However, the role of von Willebrand factor (vWF) mediated glycolysis mechanism in liver cancer metastasis is currently unknown. Methods: Western blot was used to verify the expression of vWF in HCC cells. PAS staining, glycogen and L-lactate content assays were used to reflect cellular glycolysis levels. The ability of cell migration was explored by Wound-healing and Transwell assays. Besides, the effect of vWF on the progression of HCC in vivo was also studied using subcutaneous xenograft model. Results: vWF derived from HCC cells promoted tumor migration by mediating glycolysis. Besides, vWF participated in the crosstalk between HCC cells and HSCs. HCC cells activated HSCs through vWF-mediated TGFB1 expression and secretion, and activated HSCs upregulated vWF expression in HCC cells through IL-6 secretion feedback. Further, in vitro and in vivo experiments also confirmed the importance of the JAK1/vWF/TGFB1 axis in regulating HSCs-derived IL-6 mediated HCC migration and growth. Conclusion: In summary, this article demonstrated that IL-6 released from hepatic stellate cells enhanced glycolysis and migration ability of liver cancer cells by activating JAK1/vWF/TGFB1 axis which may also be a potential target for inhibiting liver cancer metastasis.
Keywords: glycolysis, crosstalk, vWF, migration
目的:肝细胞癌(HCC)细胞与肝星状细胞(HSCs)之间的串联是肝癌转移的重要机制之一。肝癌转移与糖酵解之间的关系近来已得到广泛研究。然而,von Willebrand因子(vWF)介导的糖酵解机制在肝癌转移中的作用目前尚不清楚:方法:采用 Western 印迹法检测 HCC 细胞中 vWF 的表达。方法:用 Western blot 验证 HCC 细胞中 vWF 的表达,用 PAS 染色、糖原和 L-乳酸含量测定反映细胞的糖酵解水平。通过伤口愈合和 Transwell 试验检测细胞迁移能力。此外,还利用皮下异种移植模型研究了 vWF 对 HCC 在体内进展的影响。此外,vWF 还参与了 HCC 细胞与造血干细胞之间的串联。HCC细胞通过vWF介导的TGFB1表达和分泌激活造血干细胞,激活的造血干细胞通过IL-6分泌反馈上调HCC细胞中vWF的表达。此外,体外和体内实验也证实了JAK1/vWF/TGFB1轴在调节造血干细胞衍生的IL-6介导的HCC迁移和生长中的重要性:综上所述,本文证明了肝星状细胞释放的IL-6通过激活JAK1/vWF/TGFB1轴增强了肝癌细胞的糖酵解和迁移能力,这也可能是抑制肝癌转移的潜在靶点。
{"title":"IL-6 Released from Hepatic Stellate Cells Promotes Glycolysis and Migration of HCC Through the JAK1/vWF/TGFB1 Axis","authors":"Yifei Zhu, Jiayi Gu, Yuxin Lu, Qianying Tao, Xinliang Cao, Yanqing Zhu, Mu-qing Yang, Xin Liang","doi":"10.2147/jhc.s464880","DOIUrl":"https://doi.org/10.2147/jhc.s464880","url":null,"abstract":"<strong>Purpose:</strong> The crosstalk between hepatocellular carcinoma (HCC) cells and hepatic stellate cells (HSCs) is one of the important mechanisms of liver cancer metastasis. The relationship between liver cancer metastasis and glycolysis has been extensively studied recently. However, the role of von Willebrand factor (vWF) mediated glycolysis mechanism in liver cancer metastasis is currently unknown.<br/><strong>Methods:</strong> Western blot was used to verify the expression of vWF in HCC cells. PAS staining, glycogen and L-lactate content assays were used to reflect cellular glycolysis levels. The ability of cell migration was explored by Wound-healing and Transwell assays. Besides, the effect of vWF on the progression of HCC in vivo was also studied using subcutaneous xenograft model.<br/><strong>Results:</strong> vWF derived from HCC cells promoted tumor migration by mediating glycolysis. Besides, vWF participated in the crosstalk between HCC cells and HSCs. HCC cells activated HSCs through vWF-mediated TGFB1 expression and secretion, and activated HSCs upregulated vWF expression in HCC cells through IL-6 secretion feedback. Further, in vitro and in vivo experiments also confirmed the importance of the JAK1/vWF/TGFB1 axis in regulating HSCs-derived IL-6 mediated HCC migration and growth.<br/><strong>Conclusion:</strong> In summary, this article demonstrated that IL-6 released from hepatic stellate cells enhanced glycolysis and migration ability of liver cancer cells by activating JAK1/vWF/TGFB1 axis which may also be a potential target for inhibiting liver cancer metastasis.<br/><br/><strong>Keywords:</strong> glycolysis, crosstalk, vWF, migration<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"40 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546420","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}
Jiachen Ge, Ming Tao, Gaolei Zhang, Jianping Cai, Deyu Li, Lianyuan Tao
Purpose: Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC. Materials and Methods: We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells. Results: We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis. Conclusion: CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.
{"title":"New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma","authors":"Jiachen Ge, Ming Tao, Gaolei Zhang, Jianping Cai, Deyu Li, Lianyuan Tao","doi":"10.2147/jhc.s459150","DOIUrl":"https://doi.org/10.2147/jhc.s459150","url":null,"abstract":"<strong>Purpose:</strong> Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC.<br/><strong>Materials and Methods:</strong> We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells.<br/><strong>Results:</strong> We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis.<br/><strong>Conclusion:</strong> CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, lncRNA, T cell exhaustion, single-cell RNA-seq, machine learning, prognostic signature<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546417","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}
Ningning Wang, Yuanyuan Xu, Guangde Yang, He Chen, Xia Wang, Juanjuan Fu, Li Li, Xiucheng Pan
Purpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients’ survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient’s OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.
目的:关于质子泵抑制剂(PPIs)是否会影响免疫检查点抑制剂(ICIs)治疗肝细胞癌(HCC)的疗效的研究十分有限:我们对 2020 年 1 月 1 日至 2022 年 12 月 30 日期间接受 ICIs 联合治疗的乙型肝炎病毒(HBV)相关晚期 HCC 患者进行了回顾性分析。根据患者在接受 ICIs 治疗前后 30 天内是否接受过 PPI 治疗,将患者分为 PPI 组和非 PPI 组。评估了患者的存活率以及与 PPI 相关的死亡风险。此外,还对不良事件进行了评估:结果:共纳入183例接受ICI联合治疗的HBV相关HCC患者。PPI组和非PPI组的中位生存时间(12.5个月 vs 13.7个月,P = 0.285)和不良事件发生率(P = 0.729)无显著差异。即使经过倾向评分匹配,两组患者的中位总生存期(OS)差异也不显著(10.7 个月 vs 11.4 个月;P = 0.596),且患者的 OS 与 PPI 应用剂量无明显关系(P > 0.05).然而,根据我们的亚组分析,在血清 HBV DNA 浓度≥ 200 IU/mL 的 HCC 患者中,使用 PPIs 会显著增加接受 ICI 联合治疗患者的死亡风险(P = 0.024).结论:结论:PPIs不会明显影响接受ICI联合治疗的HBV相关晚期HCC患者的生存预后。然而,在 HBV DNA 水平较高的患者中,PPIs 会增加死亡风险。因此,对于 HBVDNA≥200 IU/mL 的患者,应加强抗病毒治疗。关键词:肝细胞癌;免疫检查点抑制剂;质子泵抑制剂;慢性乙型肝炎病毒感染
{"title":"The Impact of Proton Pump Inhibitors on the Efficacy of Immune Checkpoint Inhibitor Combinations in Patients with HBV-Associated Advanced Hepatocellular Carcinoma","authors":"Ningning Wang, Yuanyuan Xu, Guangde Yang, He Chen, Xia Wang, Juanjuan Fu, Li Li, Xiucheng Pan","doi":"10.2147/jhc.s464033","DOIUrl":"https://doi.org/10.2147/jhc.s464033","url":null,"abstract":"<strong>Purpose:</strong> There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs.<br/><strong>Methods:</strong> We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients’ survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated.<br/><strong>Results:</strong> A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, <em>P</em> = 0.285) and incidence of adverse events (<em>P</em> = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; <em>P</em> = 0.596) and the patient’s OS is not significantly related to the dosage of PPI application (<em>P</em> > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (<em>P</em> = 0.024).<br/><strong>Conclusion:</strong> PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, immune checkpoint inhibitors, proton pump inhibitors, chronic hepatitis B virus infection<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"23 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546419","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}
Robin Schmidt, Charlie Alexander Hamm, Christopher Rueger, Han Xu, Yubei He, Luzie Alexandra Gottwald, Bernhard Gebauer, Lynn Jeanette Savic
Purpose: Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE). Patients and Methods: Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher’s exact and t-test, Kaplan–Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson’s correlation. Results: OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed. Conclusion: The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.
Keywords: cancer imaging, hepatocellular carcinoma, microvascular invasion, magnetic resonance tomography, predictive imaging biomarkers
{"title":"Decision-Tree Models Indicative of Microvascular Invasion on MRI Predict Survival in Patients with Hepatocellular Carcinoma Following Tumor Ablation","authors":"Robin Schmidt, Charlie Alexander Hamm, Christopher Rueger, Han Xu, Yubei He, Luzie Alexandra Gottwald, Bernhard Gebauer, Lynn Jeanette Savic","doi":"10.2147/jhc.s454487","DOIUrl":"https://doi.org/10.2147/jhc.s454487","url":null,"abstract":"<strong>Purpose:</strong> Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE).<br/><strong>Patients and Methods:</strong> Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher’s exact and <em>t</em>-test, Kaplan–Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson’s correlation.<br/><strong>Results:</strong> OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed.<br/><strong>Conclusion:</strong> The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.<br/><br/><strong>Keywords:</strong> cancer imaging, hepatocellular carcinoma, microvascular invasion, magnetic resonance tomography, predictive imaging biomarkers<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531920","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}
Abstract: Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance.
{"title":"Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy","authors":"Xianmei Lv, Gaochen Lan, Lujian Zhu, Qiusheng Guo","doi":"10.2147/jhc.s469449","DOIUrl":"https://doi.org/10.2147/jhc.s469449","url":null,"abstract":"<strong>Abstract:</strong> Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance. <br/><br/><strong>Keywords:</strong> ferroptosis, hepatocellular carcinoma, chemotherapy, tyrosine kinase inhibitor, immunosuppressive therapy, radiotherapy<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"148 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141504594","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}