Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-,2-,and 3-year survival rates of the research group(94.00%,84.00%,and 72.00%,respectively)were significantly greater than those of the control group(80.00%,64.00%,and 40.00%,respectively;P<0.05).Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade,history of hepatitis,number of tumors,tumor size,use of sorafenib,stage of liver cancer,histological differentiation,history of splenectomy and other basic data(P<0.05).Logistic regression analysis demonstrated that high Child-Pugh grade,tumor size(6–10 cm),history of hepatitis,no use of sorafenib,liver cancer stage IIIC,and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension(P<0.05).CONCLUSION Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates.The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade,tumor size(6-10 cm),history of hepatitis,lack of sorafenib use,liver cancer at stage IIIC,and prior splenectomy.

Identification of an immune-related gene signature for predicting prognosis and immunotherapy efficacy in liver cancer via cell-cell communication

BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in cancer.The ING family genes were identified as tumor suppressor genes.Dysregulated expression of these genes can lead to cell cycle arrest,senescence and/or apoptosis.ING family genes are promising targets for anticancer therapy.However,their role in LIHC is still not well understood.AIM To have a better understanding of the important roles of ING family members in LIHC.METHODS A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in LIHC.The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC.The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.RESULTS mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in LIHC.In 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was identified.ING1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and progression.One of the target miRNAs of ING1 was identified as hsa-miR-214-3p.Two upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were identified.At the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.CONCLUSION This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function

BACKGROUND Hepatectomy is the first choice for treating liver cancer.However,inflammatory factors,released in response to pain stimulation,may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies.AIM To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.METHODS Clinical data from patients with liver cancer admitted to Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed.Thirty-five patients underwent laparoscopic hepatectomy for liver cancer(liver cancer resection group)and 35 patients underwent medical image-guided microwave ablation(liver cancer ablation group).The short-term efficacy,complications,liver function,and immune function indices before and after treatment were compared between the two groups.RESULTS One month after treatment,19 patients experienced complete remission(CR),8 patients experienced partial remission(PR),6 patients experienced stable disease(SD),and 2 patients experienced disease progression(PD)in the liver cancer resection group.In the liver cancer ablation group,21 patients experienced CR,9 patients experienced PR,3 patients experienced SD,and 2 patients experienced PD.No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups(P>0.05).After treatment,total bilirubin(41.24±7.35 vs 49.18±8.64μmol/L,P<0.001),alanine aminotransferase(30.85±6.23 vs 42.32±7.56 U/L,P<0.001),CD4+(43.95±5.72 vs 35.27±5.56,P<0.001),CD8+(20.38±3.91 vs 22.75±4.62,P<0.001),and CD4+/CD8+(2.16±0.39 vs 1.55±0.32,P<0.001)were significantly different between the liver cancer ablation and liver cancer resection groups.CONCLUSION The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar,but liver function recovers quickly after microwave ablation,and microwave ablation may enhance immune function.

Whole-process case management effects on mental state and selfcare ability in patients with liver cancer

BACKGROUND Regarding the incidence of malignant tumors in China,the incidence of liver cancer ranks fourth,second only to lung,gastric,and esophageal cancers.The case fatality rate ranks third after lung and cervical cancer.In a previous study,the whole-process management model was applied to patients with breast cancer,which effectively reduced their negative emotions and improved treatment adherence and nursing satisfaction.METHODS In this single-center,randomized,controlled study,60 randomly selected patients with liver cancer who had been admitted to our hospital from January 2021 to January 2022 were randomly divided into an observation group(n=30),who received whole-process case management on the basis of routine nursing mea-sures,and a control group(n=30),who were given routine nursing measures.We compared differences between the two groups in terms of anxiety,depression,the level of hope,self-care ability,symptom distress,sleep quality,and quality of life.RESULTS Post-intervention,Hamilton anxiety scale,Hamilton depression scale,memory symptom assessment scale,and Pittsburgh sleep quality index scores in both groups were lower than those pre-intervention,and the observation group had lower scores than the control group(P<0.05).Herth hope index,self-care ability assessment scale-revision in Chinese,and quality of life measurement scale for patients with liver cancer scores in both groups were higher than those pre-intervention,with higher scores in the observation group compared with the control group(P<0.05).CONCLUSION Whole-process case management can effectively reduce anxiety and depression in patients with liver cancer,alleviate symptoms and problems,and improve the level of hope,self-care ability,sleep quality,and quality of life,as well as provide feasible nursing alternatives for patients with liver cancer.

Prognostic impact of preoperative nutritional and immune inflammatory parameters on liver cancer

The immune response to tissue damage or infection involves inflammation,a multifaceted biological process distinguished by immune cell activation,mediator secretion,and immune cell recruitment to the site of injury.Several blood-based immune-inflammatory biomarkers with prognostic significance in malignancies have been identified.In this issue of the World Journal of Gastrointestinal Surgery,they examined the prognosis of liver cancer radical resection in relation to pre-operative systemic immune-inflammation and nutritional risk indices.Comparing older and younger individuals often reveals compromised nutritional and immu-nological statuses in the former.Therefore,performing preoperative evaluations of the nutritional status and immunity in geriatric patients is critical.In addition to being a primary treatment modality,radical resection is associated with a sig-nificant mortality rate following surgery.Insufficient dietary consump-tion and an elevated metabolic rate within tumor cells contribute to the increased proba-bility of malnutrition associated with the ailment,consequently leading to a sub-stantial deterioration in prognosis.Recent studies,reinforce the importance of nu-tritional and immune-inflammatory biomarkers.Prior to surgical intervention,geriatric nutritional risk and systemic immune-inflammatory indices should be prioritized,particularly in older patients with malignant diseases.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway

BACKGROUND The ubiquitin-proteasome pathway(UPP)has been proven to play important roles in cancer.AIM To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes.METHODS In this study,UPP-related E1,E2,E3,deubiquitylating enzyme,and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based RESULTS Five genes(including autophagy related 10,proteasome 20S subunit alpha 8,proteasome 20S subunit beta 2,ubiquitin specific peptidase 17 like family member 2,and ubiquitin specific peptidase 8)were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer.Among training,validation,and Gene Expression Omnibus sets,the overall survival differed significantly between the high-risk and low-risk groups.The expression of the five genes was significantly associated with immunocyte infiltration,tumor stage,and postoperative recurrence.A total of 111 differentially expressed genes(DEGs)were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways.Cell division cycle 20,Kelch repeat and BTB domain containing 11,and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival.CONCLUSION We have constructed a prognosis predictive model in patients with liver cancer,which contains five genes that associate with immunocyte infiltration,tumor stage,and postoperative recurrence.

Effect of CT-Guided Microwave Ablation Combined with TACE on Liver Function and Survival of Patients with Primary Liver Cancer

Objective:To explore the effect of transarterial chemoembolization(TACE)+CT-guided microwave ablation(MWA)on treating patients with primary liver cancer.Methods:78 primary liver cancer cases were enrolled and divided into groups according to their assigned surgical plans.The control group was treated with TACE alone,and the observation group was treated with TACE+CT-guided MWA.The efficacy of the treatment and the liver function indicators and follow-up results of the patients of the two groups were compared.Results:The efficacy of the treatment received by the observation group was higher than that of the control group.Besides,the patients in the observation group exhibited better improvement in liver function indicators after 3 months of treatment.Furthermore,the survival rates of 1 and 2 years after surgery of the observation group were all higher than those of the control group(P<0.05).Conclusion:TACE combined with CT-guided MWA is more effective in treating primary liver cancer compared to TACE alone.Besides,it resulted in better improvement of liver function and long-term survival rate.Therefore,this treatment regime should be popularized.

Exploring the mechanism of action of herb pair Pinellia Ternata-Magnolia Officinalis in the treatment of liver cancer based on network pharmacology and molecular docking

Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.

Research Progress on the Relationship between Magnetic Resonance Imaging and Clinical Pathological Characteristics of Liver Cancer

Liver cancer is one of the main malignant tumors in the digestive system.Early detection and treatment have positive significance in improving patient prognosis and reducing mortality.MRI is the main method for liver cancer examination,which mainly uses computers to compare imaging of different energy regions of tumors,observe the density and signal changes of liver cancer,and the degree of tumor enhancement.In particular,various new MRI functional imaging technologies,such as diffusion-weighted imaging,perfusion weighted imaging,delayed imaging,liver cell specific contrast agent enhanced imaging,etc.,can be used at the molecular level Multiple aspects such as cell function provide clinicians with richer diagnostic information.Therefore,further comparative analysis of MRI manifestations and pathological results of liver cancer can help to gain a deeper understanding of the biological behavior of tumors and provide a basis for treatment decision-making and prognosis evaluation.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

BACKGROUND Radical surgery is the most commonly used treatment for hepatocellular carcinoma(HCC).However,the surgical effect remains not ideal,and prognostic evaluation is insufficient.Furthermore,clinical intervention is rife with uncertainty and not conducive to prolonging patient survival.AIM To explore correlations between the systemic immune inflammatory index(SII)and geriatric nutritional risk index(GNRI)and HCC operation prognosis.METHODS This retrospective study included and collected follow up data from 100 HCC.Kaplan–Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival.SII and GNRI were calculated as follows:SII=neutrophil count×platelet count/lymphocyte count;GNRI=[1.489×albumin(g/L)+41.7×actual weight/ideal weight].We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic(ROC)curves,and the relationships between the SII,GNRI,and survival rate using Kaplan–Meier survival curves.Cox regression analysis was utilized to analyze independent risk factors influencing prognosis.RESULTS After 1 year of follow-up,24 patients died and 76 survived.The area under the curve(AUC),sensitivity,specificity,and the optimal cutoff value of SII were 0.728(95%confidence interval:0.600-0.856),79.2%,63.2%,and 309.14,respectively.According to ROC curve analysis results for predicting postoperative death in HCC patients,the AUC of SII and GNRI combination was higher than that of SII or GNRI alone,and SII was higher than that of GNRI(P<0.05).The proportion of advanced differentiated tumors,tumor maximum diameter(5–10 cm,>10 cm),lymph node metastasis,and TNM stage III-IV in patients with SII>309.14 was higher than that in patients with SII≤309.14(P<0.05).The proportion of patients aged>70 years was higher in patients with GNRI≤98 than that in patients with GNRI>98(P<0.05).The 1-year survival rate of the SII>309.14 group(compared with the SII≤309.14 group)and GNRI≤98 group(compared with the GNRI>98 group)was lower(P<0.05).CONCLUSION The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Targeting the mechano-microenvironment and liver cancer stem cells:a promising therapeutic strategy for liver cancer

Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.

CK2αcauses stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway

Background:Liver cancer is one of the major causes of cancer-related deaths globally.Cancer cell stem-ness and chemotherapy resistance contribute to the high mortality.Although evidence indicates that the alpha subunit of protein kinase 2(CK2α)is involved in several human cancers,its function in liver cancer remains unknown.In the present study,we aimed to elucidate the role of CK2αin liver cancer.Methods:We examined the role of CK2αregulation in stemness and chemotherapy resistance capacity of liver cancer cells.MTT assays,tumor sphere formation assays,RT-PCR,flow cytometry,Western blotting assay,clonogenicity assay,matrigel invasion assay and bioinformatics were conducted in this study.Results:CK2αexpression in the liver cancer tissues was notably upregulated compared with that in the corresponding non-tumorous tissues.The overexpression of CK2αpromoted tumor sphere formation,increased the percentage of CD133(+)and side population cells,caused the resistance of liver cancer cells to 5-FU treatment,increased the expression levels of NANOG,OCT4,SOX2,Gli1 and Ptch1,and enhanced the ability of CD133(+)cell clone formation and invasion.Consistently,the downregulation of CK2αhad the opposite effects.CK2αsilencing inhibited the Hedgehog pathway by reducing the expression of Gli1 and Ptch1.Mechanistically,CK2αregulation on liver cancer cell stemness and chemotherapy resistance was found to be involved in the Hedgehog signaling pathway.Conclusions:Our study may bring some new insights into the occurrence of liver cancer.Furthermore,these findings suggest that targeting CK2αmay be a novel therapeutic strategy for patients with liver cancer.

Efficacy of ctDNA methylation combined with traditional detection modality to detect liver cancer among high-risk patients:A multicenter diagnostic trial

Objective:Circulating tumor DNA(ctDNA)and alpha-fetoprotein(AFP)plus ultrasound(US)have been considered to have high diagnostic accuracy for cancer detection,however,the efficacy of ctDNA methylation combined with the traditional detection modality of liver cancer has not been tested in a Chinese independent cohort.Methods:The high-risk individuals aged between 35 and 70 years who were diagnosed with liver cirrhosis or had moderate and severe fatty liver were eligible for inclusion.All participants were invited to receive a traditional examination[referring to AFP plus US],and ctDNA methylation,respectively.The sensitivity and specificity of different diagnostic tools were calculated.The logistic regression model was applied to estimate the area under the curve(AUC),which was further validated by 10-fold internal cross-validation.Results:A total of 1,205 individuals were recruited in our study,and 39 participants were diagnosed with liver cancer.The sensitivity of AFP,US,US plus AFP,and the combination of US,AFP,and ctDNA methylation was33.33%,56.41%,66.67%,and 87.18%,respectively.The corresponding specificity of AFP,US,US plus AFP,and the combination of all modalities was 98.20%,99.31%,97.68%,and 97.68%,respectively.The AUCs of AFP,US,US plus AFP,and the combination of AFP,US,and ctDNA methylation were 65.77%,77.86%,82.18%,and92.43%,respectively.The internally validated AUCs of AFP,US,US plus AFP,and the combination of AFP,US,and ctDNA methylation were 67.57%,83.26%,86.54%,and 93.35%,respectively.Conclusions:The ctDNA methylation is a good complementary to AFP and US for the detection of liver cancer.