Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver di...Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.展开更多
Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Not...Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.展开更多
Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative res...Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify geno...BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.展开更多
BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular c...BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.展开更多
Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,...Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.展开更多
Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treat...Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.展开更多
Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. Ho...Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.展开更多
BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated a...BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.展开更多
Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors...Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvi...In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like ot...MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.展开更多
BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatme...Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with ...Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.展开更多
BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and tre...BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an H...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.展开更多
基金Supported by European-Latin American ESCALON Consortium,EU Horizon 2020 Program,No.825510National Institutes of Health,No.NIH R21 TW012390-01A1.
文摘Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.
文摘Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.
基金the Specific Research Project of Guangxi for Research Bases and Talents,No.GuiKe AD22035057the National Natural Science Foundation of China,No.82060510 and No.82260569.
文摘Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
文摘BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.
基金Supported by Key Projects of Natural Science Foundation of Bengbu Medical College,No.2021byzd050Science and Technological Fund of Anhui Province for Outstanding Youth,No.2008085J37.
文摘BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.
文摘Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
文摘Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.
基金supported by the National Natural Science Foundation of China(Grant No:81903643)the“Young Talent Support Plan”of Xi'an Jiaotong University,the Shaanxi Province Science and Technology Development Plan Project(Grant No.:2022ZDLSF05-05)+1 种基金the Project of Shaanxi Provincial Administration of Traditional Chinese Medicine(Project No.:2021-03-ZZ-002)the Shaanxi Province Science Fund for Distinguished Young Scholars(Grant No:2023-JC-JQ-59).
文摘Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.
文摘BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.
基金This study was supported by Beijing Municipal Science&Technology Commission to Huiguo Ding(Z221100007422002)Beijing Hospitals Authority Youth Programme to Shanshan Wang(QML20211701).
文摘Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
基金Supported by the National Natural Science Foundation of China,No.82303441Natural Science Foundation of Shanghai Municipality,No.21ZR1459100 and No.22ZR1457900+1 种基金Science and Technology Commission of Shanghai Municipality,No.20DZ2254500Shanghai Anticancer Association EYAS Project.
文摘In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
文摘MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
文摘Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.
基金Supported by Xi'an Jiaotong University Medical"Basic-Clinical"Integration Innovation Project,No.YXJLRH2022067Shaanxi Postdoctoral Research Program“Orlistat-loaded Nanoparticles as A Targeted Therapeutical Strategy for The Enhanced Treatment of Liver Cancer”,No.2023BSHYDZZ09.
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.
基金the Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.
基金National Natural Science Foundation of China,No.81460132Yunnan Pacific Department of Science,Technology-Kunming Medical University Applied Basic Research Joint Special Fund Project,No.2018FE001(-224).
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.
