Journal of Hepatocellular Carcinoma最新文献

{"title":"Efficacy and Safety of Transarterial Chemoembolization and Repeated Partial Splenic Embolization for Hepatocellular Carcinoma with Hypersplenism and Thrombocytopenia.","authors":"Wei Hong, Zizhuo Wang, Wei Yao, Xin Zhang, Lijie Zhang, Bin Liang","doi":"10.2147/JHC.S455461","DOIUrl":"10.2147/JHC.S455461","url":null,"abstract":"<p><strong>Aim: </strong>Partial splenic embolization (PSE) combined with transarterial chemoembolization (TACE) has been reported in treatment of hepatocellular carcinoma (HCC) with cirrhotic hypersplenism and thrombocytopenia. However, efficacy and safety of repeated PSE when required are unclear. This study aims to investigate post-procedural changes in peripheral blood cell and hepatic function, progression-free survival (PFS), and safety of HCC patients with hypersplenism received TACE and repeated PSE compared to those received TACE alone.</p><p><strong>Methods: </strong>This retrospective study included 102 HCC patients with hypersplenism who received TACE (n = 73) or TACE+PSE (n = 29) from January 2014 to December 2021. Changes in peripheral blood cell and hepatic function were investigated at 1 week, 2, 6, 12, 18, and 24 months. TACE procedure sessions and adverse events were recorded. PFS and prognostic factors were analyzed.</p><p><strong>Results: </strong>Despite response to initial PSE being limited, repeated PSE increased platelet (PLT) again, which peaked at 18 months. It also continued to improve red blood cell (RBC) and hemoglobin, which showed significant differences in changes from baseline between two groups until 24 months, as well as Child-Pugh scores at 12 and 18 months. Mean TACE procedure sessions were significantly higher in TACE+PSE group than that in TACE alone group (4.55 vs 3.26, <i>P</i> = 0.019). TACE+PSE group had longer median PFS (19.4 vs 9.5 months, <i>P</i> = 0.023) than TACE alone group, where PSE was an independent protective factor (HR, 0.508; <i>P</i> = 0.014). Initial and repeated PSE showed no significant differences in safety.</p><p><strong>Conclusion: </strong>Repeated PSE is effective in increasing PLT again and improving RBC, hemoglobin and liver function. It contributed to performing serial TACE procedures thereafter. TACE combined with repeated PSE has significantly longer PFS than TACE alone, where PSE was an independent protective factor. Moreover, the safety of repeated PSE was comparable to initial PSE.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1065-1078"},"PeriodicalIF":4.1,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331106","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}

{"title":"Development and Validation of a Novel Prognostic Nomogram Based on Platelet and CD8⁺T Cell Counts in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis.","authors":"Wanxin Shi, Huiwen Yan, Xiaoli Liu, Lihua Yu, Yuqing Xie, Yuan Wu, Yuling Liang, Zhiyun Yang","doi":"10.2147/JHC.S452688","DOIUrl":"10.2147/JHC.S452688","url":null,"abstract":"<p><strong>Purpose: </strong>Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8⁺T cells (CD8⁺Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8⁺Ts on PVTT prognosis.</p><p><strong>Patients and methods: </strong>This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan-Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed.</p><p><strong>Results: </strong>We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8⁺Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (<100*10^9/L) and high CD8⁺Ts (>320 cells/μL) had a better prognosis.</p><p><strong>Conclusion: </strong>We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8⁺Ts, and found that PT-8 formed by PLT and CD8⁺Ts was an excellent predictor of the prognosis of PVTT.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1049-1063"},"PeriodicalIF":4.1,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306122","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}

{"title":"LAYN Serves as a Prognostic Biomarker and Downregulates Tumor-Infiltrating CD8⁺ T Cell Function in Hepatocellular Carcinoma.","authors":"Shuxiu Xiao, Lili Lu, Zhiyuan Lin, Xinming Ye, Sheng Su, Chenlu Zhang, Yang You, Wei Li, Xiaowu Huang, Weizhong Wu, Yuhong Zhou","doi":"10.2147/JHC.S464806","DOIUrl":"10.2147/JHC.S464806","url":null,"abstract":"<p><strong>Background: </strong>Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8⁺ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8⁺ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.</p><p><strong>Methods: </strong>TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN⁺CD8⁺ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.</p><p><strong>Results: </strong>The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8⁺ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8⁺ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN⁺CD8⁺ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8⁺ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8⁺ T cells.</p><p><strong>Conclusion: </strong>LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"1031-1048"},"PeriodicalIF":4.1,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300819","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}

{"title":"Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma","authors":"Bang-Bin Chen, Po-Chin Liang, Tiffany Ting-Fang Shih, Tsung-Hao Liu, Ying-Chun Shen, Li-Chun Lu, Zhong-Zhe Lin, Chiun Hsu, Chih-Hung Hsu, Ann-Lii Cheng, Yu-Yun Shao","doi":"10.2147/jhc.s462470","DOIUrl":"https://doi.org/10.2147/jhc.s462470","url":null,"abstract":"<strong>Purpose:</strong> We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib.<br/><strong>Patients and Methods:</strong> Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics.<br/><strong>Results:</strong> The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, <em>p</em> = 0.024) and durable clinical benefit (52.8% vs 25.7%, <em>p</em> = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate (<em>p</em> = 0.028) and multivariate (<em>p</em> = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS (<em>p</em> = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group.<br/><strong>Conclusion:</strong> Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.<br/><br/><strong>Plain Language Summary:</strong> The study provides significant evidence that an increase in spleen volume is associated with better treatment outcomes in advanced hepatocellular carcinoma patients undergoing immunotherapy. These findings offer oncologists a new potential biomarker for optimizing treatment strategies. Specifically, increased spleen volume could be used to predict higher rates of disease control and durable clinical benefits, allowing for more personalized care. <br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, immunotherapy, sorafenib, response, survival<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"74 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259850","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}

{"title":"Prolonged Complete Remission Using Tislelizumab for Hepatocellular Carcinoma After Adjuvant Chemotherapy Failure: A Case Report","authors":"Xianmin Zhu, Shuang Dong, Jing Tang, Rong Xie, Huijing Wu, Jun Guan, Sheng Hu","doi":"10.2147/jhc.s464519","DOIUrl":"https://doi.org/10.2147/jhc.s464519","url":null,"abstract":"<strong>Abstract:</strong> In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"25 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259199","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}

{"title":"A Comparison of Presentation, Treatment, and Survival After Hepatocellular Carcinoma of Viral and Non-Viral Etiology in Damietta, Egypt, 2007–2019","authors":"Kévin Jean, Ahmed Tawheed, Liem Binh Luong Nguyen, Tarek Heikal, Usama Eldaly, Neveen Gaber Elhadidy, Ahmed Elghaieb, Ahmed Aboudonia, Laura Tondeur, Amélie Dublineau, Arnaud Fontanet, Mohamed El-Kassas","doi":"10.2147/jhc.s455832","DOIUrl":"https://doi.org/10.2147/jhc.s455832","url":null,"abstract":"<strong>Context:</strong> The difference in prognosis between patients diagnosed with viral versus non-viral hepatocellular carcinoma (HCC) in Egypt remains unclear.<br/><strong>Methods:</strong> We used data from patients diagnosed with HCC between 2007 and 2019 from a large monocentric retrospective cohort at the Damietta Oncology referral center (northern Egypt). Presentation and treatment were compared between viral versus non-viral etiology HCC patients. Survival was compared relying on univariate and multivariate Cox regressions.<br/><strong>Results:</strong> Data from 4714 HCC patients were analyzed. Among them, 204 (4.3%) presented with a non-viral etiology. Patients with non-viral versus viral etiology had a similar presentation overall, especially regarding the BCLC stage at HCC diagnosis. After controlling for various individual characteristics, patients with non-viral versus viral etiology had poorer survival (adjusted Hazard Ratio: 1.244; 95% Confidence Interval: 1.069– 1.447).<br/><strong>Conclusion:</strong> Despite similar features, patients with non-viral- related HCC had poorer survival compared to patients with viral-related HCC.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, liver cancer, viral etiology, non-viral etiology, survival, epidemiology<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"15 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187967","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}

{"title":"CRISPR in Targeted Therapy and Adoptive T Cell Immunotherapy for Hepatocellular Carcinoma","authors":"Fahreddin Palaz, Mehmet Ozsoz, Ali Zarrinpar, Ilyas Sahin","doi":"10.2147/jhc.s456683","DOIUrl":"https://doi.org/10.2147/jhc.s456683","url":null,"abstract":"<strong>Abstract:</strong> Despite recent therapeutic advancements, outcomes for advanced hepatocellular carcinoma (HCC) remain unsatisfactory, highlighting the need for novel treatments. The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene-editing technology offers innovative treatment approaches, involving genetic manipulation of either cancer cells or adoptive T cells to combat HCC. This review comprehensively assesses the applications of CRISPR systems in HCC treatment, focusing on in vivo targeting of cancer cells and the development of chimeric antigen receptor (CAR) T cells and T cell receptor (TCR)-engineered T cells. We explore potential synergies between CRISPR-based cancer therapeutics and existing treatment options, discussing ongoing clinical trials and the role of CRISPR technology in improving HCC treatment outcomes with advanced safety measures. In summary, this review provides insights into the promising prospects and current challenges of using CRISPR technology in HCC treatment, with the ultimate goal of improving patient outcomes and revolutionizing the landscape of HCC therapeutics.<br/><br/><strong>Keywords:</strong> CRISPR, hepatocellular carcinoma, HCC, targeted cancer therapy, adoptive T cell immunotherapy, CAR T cell therapy<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"3 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187796","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}

{"title":"A Post-International Gastrointestinal Cancers’ Conference (IGICC) Position Statements","authors":"Suayib Yalcin, Sahin Lacin, Ahmed Omar Kaseb, Bora Peynircioğlu, Murat Cantasdemir, Barbaros Erhan Çil, Pervin Hurmuz, Ahmet Bülent Doğrul, Murat Fani Bozkurt, Hüseyin Abali, Okan Akhan, Halis Şimşek, Berksoy Sahin, Faruk N Aykan, İdris Yücel, Gürkan Tellioğlu, Fatih Selçukbiricik, Philip A Philip","doi":"10.2147/jhc.s449540","DOIUrl":"https://doi.org/10.2147/jhc.s449540","url":null,"abstract":"<strong>Abstract:</strong> Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40– 50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient’s medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, screening, imaging, diagnosis, treatment, immunotherapy, tyrosine kinase inhibitors<br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"14 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141168145","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}

{"title":"Construction of a Prognostic Model for Hepatocellular Carcinoma Based on Macrophage Polarization-Related Genes","authors":"Han Chen, Jianhao Li, Dan Cao, Hong Tang","doi":"10.2147/jhc.s453080","DOIUrl":"https://doi.org/10.2147/jhc.s453080","url":null,"abstract":"<strong>Background:</strong> The progression of hepatocellular carcinoma (HCC) is related to macrophage polarization (MP). Our aim was to identify genes associated with MP in HCC patients and develop a prognostic model based on these genes.<br/><strong>Results:</strong> We successfully developed a prognostic model consisting of six MP-related genes (SCN4A, EBF3, ADGRB2, HOXD9, CLEC1B, and MSC) to calculate the risk score for each patient. Patients were then classified into high- and low-risk groups based on their median risk score. The performance of the MP-related prognostic model was evaluated using Kaplan-Meier and ROC curves, which yielded favorable results. Additionally, the nomogram demonstrated good clinical effectiveness and displayed consistent survival predictions with actual observations. Gene Set Enrichment Analysis (GSEA) revealed enrichment of pathways related to KRAS signaling downregulation, the G2M checkpoint, and E2F targets in the high-risk group. Conversely, pathways associated with fatty acid metabolism, xenobiotic metabolism, bile acid metabolism, and adipogenesis were enriched in the low-risk group. The risk score positively correlated with the number of invasion-related genes. Immune checkpoint expression differed significantly between the two groups. Patients in the high-risk group exhibited increased sensitivity to mitomycin C, cisplatin, gemcitabine, rapamycin, and paclitaxel, while those in the low-risk group showed heightened sensitivity to doxorubicin. These findings suggest that the high-risk group may have more invasive HCC with greater susceptibility to specific drugs. IHC staining revealed higher expression levels of SCN4A in HCC tissues. Furthermore, experiments conducted on HepG2 cells demonstrated that supernatants from cells with reduced SCN4A expression promoted M2 macrophage polarization marker, CD163 in THP-1 cells. Reduced SCN4A expression induced HCC-related genes, while increased SCN4A expression reduced their expression in HepG2 cells.<br/><strong>Conclusion:</strong> The MP-related prognostic model comprising six MPRGs can effectively predict HCC prognosis, infer invasiveness, and guide drug therapy. SCN4A is identified as a suppressor gene in HCC.<br/><br/>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"148 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140926604","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}

{"title":"Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).","authors":"Srinivas Chava, Nergiz Ekmen, Pauline Ferraris, Yucel Aydin, Krzysztof Moroz, Tong Wu, Swan N Thung, Srikanta Dash","doi":"10.2147/JHC.S452152","DOIUrl":"10.2147/JHC.S452152","url":null,"abstract":"<p><strong>Introduction: </strong>Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC) treatment, encounters resistance in many patients. Deciphering the mechanisms underlying sorafenib resistance is crucial for devising alternative strategies to overcome it.</p><p><strong>Aim: </strong>This study aimed to investigate sorafenib resistance mechanisms using a diverse panel of HCC cell lines.</p><p><strong>Methods: </strong>HCC cell lines were subjected to continuous sorafenib treatment, and stable cell lines (Huh 7.5 and Huh 7PX) exhibiting sustained growth in its presence were isolated. The investigation of drug resistance mechanisms involved a comparative analysis of drug-targeted signal transduction pathways (EGFR/RAF/MEK/ERK/Cyclin D), sorafenib uptake, and membrane expression of the drug uptake transporter.</p><p><strong>Results: </strong>HCC cell lines (Huh 7.5 and Huh 7PX) with a higher IC50 (10μM) displayed a more frequent development of sorafenib resistance compared to those with a lower IC50 (2-4.8μM), indicating a potential impact of IC50 variation on initial treatment response. Our findings reveal that activated overexpression of Raf1 kinases and impaired sorafenib uptake, mediated by reduced membrane expression of organic cation transporter-1 (OCT1), contribute to sorafenib resistance in HCC cultures. Stable expression of the drug transporter OCT1 through cDNA transfection or adenoviral delivery of OCT1 mRNA increased sorafenib uptake and successfully overcame sorafenib resistance. Additionally, consistent with sorafenib resistance in HCC cultures, cirrhotic liver-associated human HCC tumors often exhibited impaired membrane expression of OCT1 and OCT3.</p><p><strong>Conclusion: </strong>Intrinsic differences among HCC cell clones, affecting sorafenib sensitivity at the expression level of Raf kinases, drug uptake, and OCT1 transporters, were identified. This study underscores the potential of HCC tumor targeted OCT1 expression to enhance sorafenib treatment response.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"839-855"},"PeriodicalIF":4.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916552","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}