Transcatheter Arterial Chemoembolization Therapy Research Articles

A Hypoxia-Related miRNA-mRNA Signature for Predicting the Response and Prognosis of Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma.

Transcatheter arterial chemoembolization (TACE) is commonly used in the treatment of hepatocellular carcinoma (HCC). However, not all patients respond to this treatment. TACE typically leads to hypoxia in the tumor microenvironment. Therefore, we aimed to construct a prognostic model based on hypoxia-related differentially expressed microRNA (miRNAs) in hepatocellular carcinoma (HCC) and to investigate the potential target mRNAs for predicting TACE response. The hypoxia-related miRNAs (HRMs) were identified in liver cancer cells, then global test was performed to further select the miRNAs which were associated with recurrence and vascular invasion. A prognostic model was constructed based on multivariate Cox regression analysis; qRT-PCR analysis was used to validate the differentially expressed miRNAs in HCC cell lines under hypoxic condition. We further identified the putative target genes of the miRNAs and investigate the relationship between the target genes and TACE response, immune cells infiltration. We established a HRMs prognostic model for HCC patients, containing two miRNAs (miR-638, miR-501-5p), the patients with high-HRMs score showed worse survival in discovery and validation cohort; qRT-PCR analysis confirmed that these two miRNAs are up-regulated in hepatoma cells under hypoxic condition. Furthermore, four putative target genes of these two miRNAs were identified (ADH1B, CTH, FTCD, RCL1), which were significantly associated with TACE response, immune score, immunosuppressive immune cells infiltration, PDCD1 and CTLA4. The HCC-HRMs signature may be utilized as a promising prognostic factor and may have implications for guiding TACE and immune therapy.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma.

Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC. To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC. This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed. The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05). TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

Higher Indocyanine Green Retention Is Associated with Improved Prognosis in Patients with Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization

PurposeTo test indocyanine green retention rate at 15 minutes (ICG-R15) as a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) therapy. Materials and MethodsThis retrospective cohort study was performed on the data of 278 consecutive patients with HCC treated with TACE after ICG-R15 testing at a single university hospital. Cox proportional hazard model analysis was performed to identify independent prognostic factors. After adjusting for age, sex, stage of HCC, albumin–bilirubin score, etiologies, and baseline year by propensity score matching, the prognostic impact of higher ICG-R15 was evaluated using the Kaplan–Meier curve. ResultsUnivariate and multivariate analyses identified higher ICG-R15 as a positive prognostic factor for overall survival. Propensity score matching generated two 77-patient cohorts: ICG-R15 <20% group and ICG-R15 >20% group. The overall survival of the ICG-R15 >20% group was significantly better than that of the ICG-R15 <20% group. ConclusionsHigher ICG-R15 acted as a positive long-term prognostic factor in patients with HCC treated with TACE.

Development of a Combined Oxidative Stress and Endoplasmic Reticulum Stress-Related Prognostic Signature for Hepatocellular Carcinoma.

Oxidative stress and endoplasmic reticulum stress are important components of the cellular stress process, which plays a critical role in tumor initiation and progression. First, the correlation between oxidative stress and endoplasmic reticulum stress was detected in 68 human hepatocellular carcinoma (HCC) tissue microarray samples by immunohistochemistry. Differentially expressed oxidative stress- and endoplasmic reticulum stressrelated genes (OESGs) then were screened in HCC. Next, an OESGs prognostic signature was constructed for HCC in the training cohort (TCGA-LIHC from The Cancer Genome Atlas), by least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses, and was verified in the external cohort (GSE14520 from the Gene Expression Omnibus). The MCP counter was employed to evaluate immune cell infiltration. The C-index was used to evaluate the predictive power of prognostic signature. Finally, a prognostic nomogram model was constructed to predict the survival probability of patients with HCC based on the results of Cox regression analysis. We demonstrated a positive correlation between oxidative stress and ER stress in human HCC samples. We then identified five OESGs as a prognostic signature consisting of IL18RAP, ECT2, PPARGC1A, STC2, and NQO1 for HCC. Related risk scores correlated with tumor stage, grade, and response to transcatheter arterial chemoembolization therapy, and the higher risk score group had less T cells, CD8+ T cells, cytotoxic lymphocytes and natural killer cell infiltration. The C-index of our OESGs prognostic signature was superior to four previously published signatures. Furthermore, we developed a nomogram based on the OESGs prognostic signature and clinical parameters for patients with HCC that is an effective quantitative analysis tool to predict patient survival. The OESGs signature showed excellent performance in predicting survival and therapeutic responses for patients with HCC.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Mapping research trends of transarterial chemoembolization for hepatocellular carcinoma from 2012 to 2021: A bibliometric analysis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-related deaths. Transcatheter arterial chemoembolization (TACE) is a therapy where drugs aimed to slow or halt tumor development are injected into the artery supplying for HCC tissues. A comprehensive analysis of all the articles on TACE for HCC can give us a general understanding of the progress in this field and provide guidance for future research. To analyze and visualize scientific results and research trends in TACE treatment for HCC. The "Web of Science" database was used to identify articles regarding TACE for the treatment of HCC from 2012 to 2021. VOSviewer and CiteSpace were used to analyze the publications trends, collaboration between countries/insti-tutions/authors, and the co-occurrence of keywords, keyword bursts, and references. A total of 5728 original articles on TACE for HCC were retrieved. Regarding the volume of publications, the total number of yearly publications showed a generally increasing trend. China had the highest number of articles, while the United States achieved the highest Hirsch index and highest number of citations. The Sun Yat-sen University in China was most prolific institution. The most active author was Park, J.W from South Korea. The Journal of Vascular and Interventional Radiology (234 articles) was the most productive journal. There is a growing trend toward international collaboration in TACE for HCC. Cluster networks of co-cited references suggested that practice guidelines and targeted therapies are an essential theme in this field. In addition, cluster analysis based on keyword co-occurrence identified the research topic "prediction of TACE treatment" as a hotspot, and propensity score matching can be used to help investigators conduct innovative studies in the future. The results of our bibliometric analysis provide the latest trends and hot topics in TACE therapy for HCC.

Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.

Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC). We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot. Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line. Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.

Identification of PANoptosis-Based Prognostic Signature for Predicting Efficacy of Immunotherapy and Chemotherapy in Hepatocellular Carcinoma.

PANoptosis has been a research hotspot, but the role of PANoptosis in hepatocellular carcinoma (HCC) remains widely unknown. Drug resistance and low response rate are the main limitations of chemotherapy and immunotherapy in HCC. Thus, construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy is necessary. The mRNA expression data of HCC patients was collected from TCGA database. Through LASSO and Cox regression, we developed a prognostic signature based on PANoptosis-related genes. KM analysis and ROC curve were implemented to evaluate the prognostic efficacy of this signature, and ICGC and GEO database were used as external validation cohorts. The immune cell infiltration, immune status, and IC50 of chemotherapeutic drugs were compared among different risk subgroups. The relationships between the signature and the efficacy of ICI therapy, sorafenib treatment, and transcatheter arterial chemoembolization (TACE) therapy were investigated. A 3-gene prognostic signature was constructed which divided the patients into low- and high-risk subgroups. Low-risk patients had better prognosis, and the risk score was proved to be an independent predictor of overall survival (OS), which had a well predictive effect. Patients in high-risk population had more immunosuppressive cells (Tregs, M0 macrophages, and MDSCs), higher TIDE score and TP53 mutation rate, and elevated activity of base excision repair (BER) pathways. Patients with low risk benefited more from ICI, TACE, and sorafenib therapy. The predictive value of the risk score was comparable with TIDE and MSI for OS under ICI therapy. The risk score could be a biomarker to predict the response to ICI, TACE, and sorafenib therapy. The novel signature based on PANoptosis is a promising biomarker to distinguish the prognosis predict the benefit of ICI, TACE, and sorafenib therapy, and forecast the response to them.

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB.

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs). Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy. Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child-Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs. Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.

Basement membrane-related regulators for prediction of prognoses and responses to diverse therapies in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) remains a global health threat. Finding a novel biomarker for assessing the prognosis and new therapeutic targets is vital to treating this patient population. Our study aimed to explore the contribution of basement membrane-related regulators (BMR) to prognostic assessment and therapeutic response prediction in HCC.Material and methodsThe RNA sequencing and clinical information of HCC were downloaded from TCGA-LIHC, ICGC-JP, GSE14520, GSE104580, and CCLE datasets. The BMR signature was created by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and used to separate HCC patients into low- and high-risk groups. We conducted analyses using various R 4.1.3 software packages to compare prognoses and responses to immunotherapy, transcatheter arterial chemoembolization (TACE), and chemotherapeutic drugs between the groups. Additionally, stemness indices, molecular functions, and somatic mutation analyses were further explored in these subgroups.ResultsThe BMR signature included 3 basement membrane-related genes (CTSA, P3H1, and ADAM9). We revealed that BMR signature was an independent risk contributor to poor prognosis in HCC, and high-risk group patients presented shorter overall survival. We discovered that patients in the high-risk group might be responsive to immunotherapy, while patients in the low-risk group may be susceptible to TACE therapy. Over 300 agents were screened to identify effective drugs for the two subgroups.ConclusionOverall, basement membrane-related regulators represent novel biomarkers in HCC for assessing prognosis, response to immunotherapy, the effectiveness of TACE therapy, and drug susceptibility.

Treatment with camrelizumab plus tyrosine kinase inhibitors with or without TACE for intermediate-advanced hepatocellular carcinoma: a clinical efficacy and safety study

Abstract Objectives This research compared the curative effect and safety of camrelizumab plus tyrosine kinase inhibitors (TKIs) combined with transcatheter arterial chemoembolization (TACE) to those of camrelizumab plus TKIs for the treatment of intermediate-advanced hepatocellular carcinoma (HCC). Methods From January 2019 to July 2021, 47 patients with intermediate-advanced HCC were included in this retrospective study. After screening, 44 eligible patients were split into two arms: the camrelizumab + TKI + TACE arm (n=28) and the camrelizumab + TKI arm (n=16). The primary endpoints were overall survival (OS) and progression-free survival (PFS), while tumor response and adverse events (AEs) served as secondary endpoints. Results The median OS was 12.60 months for the 44 patients. The median PFS (p=0.0248, 7.20 vs. 3 months), objective response rate (ORR) (21.43 vs. 6.25%) and disease control rate (DCR) (57.14 vs. 18.75%) were better for patients in the camrelizumab + TKI + TACE arm than in the camrelizumab + TKI arm. After correcting for the effects of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBil) levels, the treatment effect of the camrelizumab + TKI + TACE arm (HR=0.330, 95% CI=0.130–0.880, p=0.026) was still superior. The common AEs in the two groups included reactive cutaneous capillary hyperplasia (n=17), myelosuppression (n=19) and liver dysfunction (n=12). However, AEs of grade ≥3 were equal between the groups. Conclusions Camrelizumab + TKI + TACE therapy was more effective than camrelizumab + TKI therapy for intermediate-advanced HCC, and toxicity was manageable.

Longer Survival and Preserved Liver Function after Proton Beam Therapy for Patients with Unresectable Hepatocellular Carcinoma

Proton beam therapy (PBT) has been recently reported to achieve excellent tumor control with minimal toxicity in patients with unresectable hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) was investigated for larger HCC. This study was designed to evaluate the therapeutic effect of PBT on unresectable HCC in comparison with TACE combined with RFA. We retrospectively analyzed 70 patients with HCC which was difficult to control by surgical resection or RFA monotherapy, 24 patients treated with PBT and 46 patients with TACE plus RFA. The therapeutic effects were assessed as local progression-free survival (PFS) and overall survival (OS). The local PFS was more than 65% in 60 months for PBT and TACE plus RFA. The patients treated with PBT showed 82% OS at 60 months post-treatment. In contrast, those treated with TACE plus RFA showed 28% OS. When comparing the changes of ALBI scores in patients with different severities of chronic liver disease, the scores of PBT-treated patients were maintained at the baseline; however, those of TACE plus RFA-treated patients worsened after the treatments. The results indicated that PBT may show better benefits than TACE plus RFA therapy in terms of OS in patients with unresectable HCC by sparing the non-tumor liver tissues.

Chemoembolization combined radiofrequency ablation vs. chemoembolization alone for treatment of beyond the Milan criteria viable hepatocellular carcinoma (CERFA): study protocol for a randomized controlled trial

BackgroundMany previous studies evaluated a combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating early hepatocellular carcinoma (HCC); however, studies evaluating combination therapy for beyond-the-Milan criteria HCC are scarce.MethodsA total of 120 patients with beyond-the-Milan criteria HCC who have viable tumour after first TACE will be enrolled in this multi-institutional, parallel, pragmatic, randomized controlled trial. Patients with metastasis, vascular invasion, or a sum of tumour diameter > 8 cm will be excluded. Eligible patients will be randomly assigned to combination TACE and RFA therapy or TACE monotherapy groups. Patients in the combination therapy group will receive a second TACE and subsequent RFA at the viable tumour. Patients in the TACE monotherapy group will receive only second TACE. Patients in both groups will undergo magnetic resonance imaging 4–6 weeks after second TACE. The primary endpoint is 1-month tumour response, and secondary endpoints are progression-free survival, overall response rate, number of treatments until CR, overall survival, and change in liver function.DiscussionAlthough TACE can be used to treat intermediate-stage HCC, it is difficult to achieve CR by first TACE in most intermediate-stage patients. Recent studies show a survival advantage of combination therapy over monotherapy. However, most studies evaluating combination therapy included patients with a single tumour sized < 5 cm, and no studies included patients with intermediate-stage but more advanced (i.e., beyond-the-Milan criteria) HCC. This study will evaluate the efficacy of combined TACE and RFA therapy for patients with advanced HCC within the intermediate stage.Trial registrationClinical Research Information Service (CRiS) KCT0006483.

Analysis of factors influencing the distribution of 131-I in combined treatment of Licartin with transcatheter arterial chemoembolization in primary hepatic carcinoma.

To analyze the factors influencing the distribution of 131-I in the liver of patients with advanced hepatic carcinoma treated with the combination of Licartin (131I Metuximab) and transcatheter arterial chemoembolization (TACE). This study provides a reference and basis for the clinic on how to choose the best time for the treatment of Licartin and how to reduce other possible factors affecting the role of Licartin. Data from 41 patients with advanced hepatic carcinoma treated with the combination of Licartin and TACE in the Interventional Department of our hospital from March 2014 to December 2020 were collected. This included general characteristics, history of open and interventional surgery, interval between the last interventional surgery and the Licartin treatment, selected arteries in the Licartin perfusion, and 131-I distribution in the liver. Regression analysis was conducted to investigate the factors affecting the distribution of 131I in the liver. In 14 cases (34.1%), 131-I was evenly distributed in the liver, and there was no correlation between the cause of even distribution with age(OR=0.961, P = 0.939), previous open surgery history(OR=3.547,P= 0.128), previous history of interventional therapy(OR=0.140,P = 0.072), the interval between the last interventional surgery and the Licartin treatment(OR=0.858,P = 0.883), or the choice of the perfusion artery in the Licartin treatment (OR=1.489,P = 0.419). In 14 cases (34.1%), there was higher aggregation in the tumor than in the normal liver, which was related to previous interventional surgery (OR=7.443,P = 0.043). In 13 cases (31.7%), there was lower aggregation in the tumor than in the normal liver, which was related to the selected vessels in the Licartin perfusion (OR=0.23,P = 0.013). The effective aggregation of 131-I in the liver, even in tumors, the previous history of TACE, and the choice of vessels in the Licartin infusion might be the factors influencing the distribution of 131-I in the liver during hepatic artery infusion of Licartin in combination with TACE therapy.

Impact of particle size of multivesicular liposomes on the embolic and therapeutic effects in rabbit VX2 liver tumor

Transcatheter arterial chemoembolization (TACE) is usually considered more efficacious in the local treatment of parenchyma-sparing hepatocellular carcinoma (HCC). At present, embolic agents commonly used in TACE, include DC pellets, Hepasphere, Lipiodol, etc. Except that iodine oil is a viscous fluid embolic agent, other solid microsphere particles used clinically range from 70 to 700 µm, among which 100 to 300 µm is the most commonly used. With the technology development of micro-invasive interventional therapy, the specific distal embolization through TACE to occlude tumor arterial blood supply in patients with HCC is also required more accurately. Effective terminal embolization is considered to be a preferred option for TACE therapy due to significantly improving the survival rate of patients and preserving liver function. In this article, we prepared the multifunctional multivesicular liposomes (IVO-DOX-MVLs) (<100 µm) that can simultaneously encapsulate ioversol and doxorubicin based on the high-phase transition temperature (T m) lipid ingredients, and evaluated its local artery embolization and therapeutic effect in rabbit VX-2 tumor model. The influence of particle size on occlusion and therapeutic effect of MVLs on rabbit VX-2 liver tumor models were well evaluated, including the tumor volume change, tumor growth rate, and necrosis rate, which were evaluated by magnetic resonance (MR). MVL samples with average particle size distribution of 50–60 µm exhibited fewer off-target embolization. Through TACE, IVO-DOX-MVLs were directly transported to the tumor tissues, playing roles of embolization performance, CT imaging effect, and local tumor killing effect. The feasibility of MVLs as a multifunctional embolic agent in its clinical application can be further improved by optimization of lipid composition and preparation process.

95P Additional survival follow-up of TACTICS-L: Transcatheter arterial chemoembolization therapy (TACE) in combination strategy with lenvatinib in (LEN) patients with unresectable hepatocellular carcinoma in Japan

TACTICS-L is a prospective study to evaluate safety and efficacy of combination of TACE and LEN in HCC patients who are not eligible for curative therapy (uHCC). The primary analysis was conducted at cutoff date of April 2021 (minimum follow-up 12 months), and median progression-free survival (PFS), the primary endpoint, was 24.4 months. Regarding the secondary endpoint, the median overall survival (OS) was 25.9 months, and best objective response was 88.7% (CR 67.7%) 1). Here we report an additional follow-up on PFS and OS.

Nanoscale CaO2 materials for synergistic transarterial chemoembolization in a VX2 orthotopic rabbit liver cancer model

Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of hepatocellular carcinoma (HCC), but its efficacy is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). Herein, we synthesized polyvinyl pyrrolidone (PVP)-coated CaO2 nanoparticles (CaO2 NPs) and applied them as a synergistic agent to improve the antitumor efficacy of TACE. After injection into the tumor, CaO2 NPs reacted with water to generate abundant oxygen, hydroxyl ions (OH−), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing acid, and overloading Ca2+ to mediate antitumor effects. Moreover, the effect of chemotherapeutic drugs within the TACE was improved due to the modulated TME. CaO2 NPs efficiently regulated the TME and improved the antitumor effect of doxorubicin under hypoxia conditions in vitro. Compared to other groups, the TACE+CaO2 NPs group achieved the lowest tumor growth rate, highest tumor necrosis rate, lowest expression of histological markers associated with hypoxia and angiogenesis (HIF-α, VEGF, and CD31), and highest CD8+ T cell recruitment in vivo. Thus, these findings demonstrated that CaO2 NPs provide synergy for TACE therapy in the VX2 orthotopic rabbit liver cancer model, suggesting that they have a potential broad clinical application. Statement of significanceThe efficacy of transcatheter arterial chemoembolization (TACE) for treatment of hepatocellular carcinoma is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). To address this issue, we synthesized CaO2 nanoparticles (CaO2 NPS) which would react with water to generate abundant oxygen, hydroxyl ions (OH−), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing the acidic TME, and inducing Ca2+ overloading. The efficacy of CaO2 NPs in combination with TACE was investigated in an orthotopic rabbit liver cancer model, and the results showed the great synergetic antitumor effect of TACE and CaO2 NPs.

Relationship between M6A methylation regulator and prognosis in patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

BackgroundPatients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC. MethodsGenes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined. ResultsThe detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells. ConclusionThe response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.

A Novel Ferroptosis-Related Signature for Prediction of Prognosis, Immune Profiles and Drug Sensitivity in Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is a malignant disease with an increasing incidence and a high mortality rate. Ferroptosis, a novel type of cell death, has been reported to be closely associated with the progression of HCC. The aim of our study was to construct a novel ferroptosis-related signature (nFRGs) for prediction of prognosis, immune features and drug sensitivity of HCC patients. Data were obtained from the TCGA, ICGC, GSE104580, CCLE and IMvigor210 datasets, and the least absolute shrinkage and selection operator (LASSO) was used to construct nFRGs. In addition, the analyses involved in prognoses, molecular function, stemness indices, somatic mutation, responses to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy and drug sensitivity were performed using diverse packages of R 4.1.3 between the low- and high-risk groups. The nFRGs included seven ferroptosis-related genes. Our results showed that nFRGs was an independent risk factor for prognoses of HCC patients, and HCC patients in the high-risk group presented with worse prognosis. Compared with the results of other studies, nFRGs was superior to other promising signatures in predicting prognoses of patients with HCC. In addition, most of the enriched pathways of differentially expressed genes (DEGs) between these subgroups were related to immune features. The molecular functions, genetic mutation and mRNAsi were varied between the high- and low-risk groups. Moreover, we observed significant immunosuppression state in the high-risk group. Patients in the high-risk group might benefit from immunotherapy, whereas patients in the low-risk group may be susceptible to TACE therapy. Finally, five sensitive drugs and four sensitive drugs were screened for patients in the high- and low-risk groups, respectively. nFRGs may served as a novel biomarker of prognosis and aid in personalized therapeutic strategies for patients with HCC.

A novel signature of combing cuproptosis- with ferroptosis-related genes for prediction of prognosis, immunologic therapy responses and drug sensitivity in hepatocellular carcinoma.

BackgroundOur study aimed to construct a novel signature (CRFs) of combing cuproptosis-related genes with ferroptosis-related genes for the prediction of the prognosis, responses of immunological therapy, and drug sensitivity of hepatocellular carcinoma (HCC) patients.MethodsThe RNA sequencing and corresponding clinical data of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), GSE76427, GSE144269, GSE140580, Cancer Cell Line Encyclopedia (CCLE), and IMvigor210 cohorts. CRFs was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. The analyses involved in the prognosis, response to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy, and drug sensitivity were performed. Furthermore, the molecular function, somatic mutation, and stemness analyses were further performed between the low- and high-risk groups, respectively. In this study, the statistical analyses were performed by using the diverse packages of R 4.1.3 software and Cytoscape 3.8.0.ResultsCRFs included seven genes (G6PD, NRAS, RRM2, SQSTM1, SRXN1, TXNRD1, and ZFP69B). Multivariate Cox regression analyses demonstrated that CRFs were an independent risk factor for prognosis. In addition, these patients in the high-risk group presented with worse prognoses and a significant state of immunosuppression. Moreover, patients in the high-risk group might achieve greater outcomes after receiving immunologic therapy, while patients in the low-risk group are sensitive to TACE. Furthermore, we discovered that patients in the high-risk group may benefit from the administration of sunitinib. In addition, enhanced mRANsi and tumor mutation burden (TMB) yielded in the high-risk group. Additionally, the functions enriched in the low-risk group differed from those in the other group.ConclusionIn summary, CRFs may be regarded not only as a novel biomarker of worse prognosis, but also as an excellent predictor of immunotherapy response, efficacy of TACE and drug sensitivity in HCC, which is worthy of clinical promotion.