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Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) se ha convertido en la enfermedad hepática crónica más frecuente en los países occidentales, causando un aumento en los costos y en la ocupación hospitalaria. La caracterización integral previa al trasplante hepático en pacientes con MASLD es una gran interrogante, especialmente en nuestro medio. El objetivo del presente estudio fue realizar la caracterización clínico-epidemiológica de pacientes trasplantados por cirrosis hepática (CH) descompensada o carcinoma hepatocelular (CHC) asociado a MASLD. Metodología. Se desarrolló un estudio observacional retrospectivo, descriptivo, de corte transversal en el Servicio de Hepatología del Hospital Pablo Tobón Uribe en Medellín, Colombia. Se incluyeron pacientes mayores de 17 años, con diagnóstico de CH o de CHC asociado a MASLD que fueron trasplantados entre los años 2004 a 2017. Resultados. Se encontraron 84 pacientes que fueron trasplantados con esas características. La edad promedio de los pacientes fue de 59±10,5 con una mayor proporción significativa de hombres sobre mujeres, llegando casi al 70 %. Con relación a las comorbilidades, se encontró que el sobrepeso/obesidad, la hipertensión arterial y la diabetes mellitus tipo 2 fueron un hallazgo en el 44,1 %, 33,3 % y 33,3 %, respectivamente. Por otro lado, el 14,5 %, el 33,7 % y el 51,8 % presentaron un Child-Pugh A, B y C, respectivamente. La media del puntaje MELD fue de 18,9±6,26. Con respecto a las complicaciones de la cirrosis, el 77,4 % de los pacientes presentó ascitis, el 61,9 % encefalopatía hepática, el 36,9 % hemorragia del tracto digestivo superior y el 29,8 % peritonitis bacteriana espontánea. Conclusión. Los resultados expuestos mostraron nuestra experiencia en trasplante hepático en pacientes con CH y CHC asociado a MASLD. Se debe realizar una evaluación multidisciplinaria antes y después del trasplante en estos pacientes, haciendo especial énfasis en el manejo de la disfunción metabólica y sus componentes, entre los que se destacan la obesidad y la diabetes mellitus.
Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most frequent chronic liver disease in Western countries, causing increased costs and hospital occupancy. The comprehensive pre-transplant characterization in patients with MASLD is a major question, especially in our setting. The aim of the present study was to perform the clinical-epidemiological characterization of transplanted patients with decompensated liver cirrhosis (LC) or hepatocellular carcinoma (HCC) associated with MASLD. Methodology. A retrospective, descriptive, cross-sectional observational study was carried out in the Hepatology Department of the Pablo Tobón Uribe Hospital in Medellin, Colombia. Patients over 17 years of age, with a diagnosis of LC or HCC associated with MASLD who were transplanted between 2004 and 2017 were included. Results. We found 84 patients who were transplanted with these characteristics. The mean age of the patients was 59±10.5 with a significantly higher proportion of men over women, reaching almost 70%. Regarding comorbidities, overweight/obesity, arterial hypertension, and type 2 diabetes mellitus were found in 44.1%, 33.3%, and 33.3%, respectively. On the other hand, 14.5%, 33.7%, and 51.8% had Child-Pugh A, B, and C, respectively. The mean MELD score was 18.9±6.26. Regarding complications of cirrhosis, 77.4% of patients developed ascites, 61.9% hepatic encephalopathy, 36.9% upper gastrointestinal tract hemorrhage, and 29.8% spontaneous bacterial peritonitis. Conclusion. The above results showed our experience of liver transplantation in patients with LC and HCC associated with MASLD. A multidisciplinary evaluation should be performed before and after transplantation in these patients, with special emphasis on the management of metabolic dysfunction and its components, including obesity and diabetes mellitus.
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Non-alcoholic Fatty Liver DiseaseРеферат
Small nucleolar RNAs (snoRNAs) are non-coding RNAs in the nucleolus and are mainly responsible for the 2'-O-methylation and pseudouridine modification of rRNA. snoRNAs regulate various biological processes, such as tRNA modification, spliceosome snRNA modification, maintenance of the telomere structure, and alternative splicing of mRNA. Aberrant expression of snoRNA is related to cancer progression, and it may become a new target for cancer treatment. snoRNAs are stable and easy to detect in body fluids, so they can be used as a biomarker for clinical diagnosis and prognostic. This article reviews the biogenesis, classification, structure, and function of snoRNAs and introduces their potential role in the occurrence and development of hepatocellular carcinoma.
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Liver transplantation is the optimal treatment for end-stage liver disease and hepatocellular carcinoma, which can significantly improve clinical prognosis and quality of life of patients. However, multiple challenges, such as rejection, immune tolerance, shortage of donor liver, preservation of donor liver, ischemia-reperfusion injury and postoperative complications, <i>etc.</i>, limit the efficacy of liver transplantation in clinical practice. Research teams in China have made significant contributions to the basic research related to liver transplantation by making continuous efforts and combining the development of emerging technologies, interdisciplinary integration and other emerging fields. In this article, the frontier progress in the basic research of liver transplantation in 2023 was reviewed, highlighting the progress made by Chinese research teams in the basic research of liver transplantation, aiming to provide reference for promoting the integration of Chinese characteristics into the research of liver transplantation, accelerate the integration of Chinese liver transplantation research with international community, and promote further advancement of liver transplantation in China.
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As a mature organ transplantation, liver transplantation has become the optimal treatment for end-stage liver disease, which can improve the quality of life of recipients. However, liver transplantation still faces multiple challenges, such as rejection, infection, biliary complications, delayed graft function, ischemia-reperfusion injury, recurrence of hepatocellular carcinoma after liver transplantation, kidney-related diseases after transplantation, and donor shortage, <i>etc.</i>, which remain to be improved and urgently resolved. With persistent attempts and experience accumulated by Chinese experts and scholars, these problems related to liver transplantation have been gradually resolved year by year. In 2023, liver transplantation teams in China have achieved a series of significant progresses in the field of clinical research. In this article, clinical frontiers and novel technological progresses in the field of liver transplantation in 2023 were reviewed, and the achievements of clinical liver transplantation in China in 2023 were summarized, aiming to provide novel ideas for promoting further development of liver transplantation in China.
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ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model， cisplatin， low- （4 g·kg-1·d-1）， medium- （8 g·kg-1·d-1）， and high-dose （16 g·kg-1·d-1） modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days， the mice were sacrificed on day 15. The tumor volume was measured on days 0， 4， 8， 12， 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells， and the tumor cell-killing rate was detected by the cell counting kit-8 （CCK-8）. Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 （PD-1） and lymphocyte activation gene-3 （LAG-3） in spleen and tumor tissues. The number of CD4+ and CD8+ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry （IHC）. ResultOn day 8 of drug administration， tumor volumes in all treatment groups decreased compared with that in the model group. On day 15， both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group （P<0.01）， with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups， medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index （P<0.01）. Compared with the model group， all treatment groups showed increased spleen index （P<0.05， P<0.01）， with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups， all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4+ and CD8+ T cells and tumor cell-killing rate in the spleen and tumor tissues （P<0.01） and down-regulated mRNA and protein levels of LAG-3 （P<0.05， P<0.01）. The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups （P<0.01）. ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4+ and CD8+ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression， thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.
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Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.
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Objective:To discuss the factors related to the prognosis in the alpha fetoprotein(AFP)negative hepatocellular carcinoma(HCC)patients,and to construct the nomogram for predicting the survival time of the patients.Methods:The retrospective analysis on data of 2 064 cases of AFP negative HCC patients extracted from the Surveillance,Epidemiology,and End Results(SEER)Database was conducted,and all the patients were divided into training cohort and internal validation cohort at a ratio of 7∶3,and 101 AFP negative HCC patients from the Integrated Traditional Chinese and Western Medicine Hospital in Hunan Province were regarded as the external validation cohort.The univariate Cox regression analysis results were incorporated into the multivariate analysis,and the independent risk factors for the AFP negative HCC patients were obtained by multivariate Cox analysis to build a cancer specific survival(CSS)prognosis nomogram for the AFP negative HCC patients.The predictive efficacy and clinical utility of the nomogram were evaluated by time-dependent receiver operating characteristic curve(ROC),calibration plots,and decision curve analysis(DCA).The total score obtained from the nomogram was used for the risk stratification to compare the degree of risk discrimination between the nomogram and the American Joint Committee on Cancer(AJCC)staging system.Results:Ten independent risk factors were selected by multivariate Cox regression analysis to construct 3-year,4-year,and 5-year CSS prognostic nomograms for the AFP negative HCC patients,including the patient's age,pathological grade,surgical status,radiotherapy status,chemotherapy status,lung metastasis status,tumor size,tumor T stage,tumor M stage,and marital status.The area under curve(AUC)for the 3-year,4-year,and 5-year time-dependent ROC in the training cohort were 0.807(95%CI:0.786-0.828),0.804(95%CI:0.782-0.826),and 0.813(95%CI:0.790-0.835),respectively.In the internal validation cohort,they were 0.776(95%CI:0.743-0.810),0.772(95%CI:0.737-0.808),and 0.789(95%CI:0.752-0.826),and in the external validation cohort,they were 0.773(95%CI:0.677-0.868),0.746(95%CI:0.620-0.872),and 0.736(95%CI:0.577-0.895).The calibration plots verified that the nomogram fitted well with the perfect line.The DCA curve revealed that the net benefit of the nomogram was significatly higer than that of the AJCC staging system at certain probability thresholds compared with AJCC staging,the nomogram had a better ability to identify high-risk individuals.Conclusion:The serum AFP expression is one of the prognostic markers for the HCC patients.For those patients with AFP negative expression in serum,different considerations should be taken.The nomogram model based on multiple risk factors is a promising clinical tool for assessing the CSS in the AFP negative HCC patients.
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Objective To study the effect of NAD(P)H:quinone oxidoreductase 1(NQO1)expression lev-el on prognosis in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 103 patients with HBV-HCC underwent surgical treatment in Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from March 2019 to January 2020 were enrolled.The cancer tissue and adjacent normal tissues were extracted during surgery.Immunohistochemical staining was used to detect the expression of NQO1 in tissues.The clinical and pathological data of patients were collected,and the rela-tionships between high and low expression of NQO1 and pathological characteristics were discussed.A 3-year follow-up was conducted,and the Kaplan-Meier survival curve was drawn and Log-rank test was conducted on median survival time.Then COX model analysis was used to analyze the factors affecting the prognosis of HBV-HCC patients.Results The positive rate of NQO1 in HBV-HCC tissues was 84.47％(87/103)and the high expression rate was 59.22％(61/103).The positive rate and the high expression rate of NQO1 in HBV-HCC tissues were higher than those in adjacent normal tissues(P＜0.05).There were statistically significant differences in tumor maximum diameter,number of lesions,American Joint Committee on Cancer(AJCC)staging,and vascular invasion between patients with high and low expression of NQO1(P＜0.05).The 3-year follow-up results denoted that the median survival time of patients was 37 months,and no cases were lost in follow-up.Among 103 patients,there were 34 dead cases with an overall survival rate of 66.99％(69/103)and 42 recurrence cases with a recurrence-free survival rate of 59.23％(61/103).Kaplan-Meier survival curve re-sults showed that the overall survival rate and recurrence-free survival rate were 52.46％(32/61)and 50.82％(31/61)in NQO1 high expression group,which were lower than 88.10％(37/42)and 71.43％(30/42)in NQO1 low expression group(P＜0.05).COX model analysis results showed that high expression of NQO1,tumor maximum diameter ≥5 cm,multiple lesions,AJCC stage Ⅲ to Ⅳ and vascular invasion were independ-ent risk factors for prognosis(P＜0.05).Conclusion NQO1 is highly expressed in HBV-HCC tissue,and is related to the clinicopathological characteristics of patients,so it could be used as an independent biomarker for evaluating prognosis.
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Objective To investigate the expression of cysteine-rich intestinal protein 1(CRIP1),STIP1 ho-mology and U-box protein 1(STUB1)in cancer tissues of patients with hepatocellular carcinoma and their clinical prognostic significance.Methods From February 2018 to February 2020,112 patients with hepatocel-lular carcinoma were selected as the study objects.The expression of CRIP1 and STUB1 in cancer tissues and adjacent tissues of patients with hepatocellular carcinoma was detected by immunohistochemistry.To analyze the relationship between the expression of CRIP1 and STUB1 and their clinicopathological features in hepato-cellular carcinoma patients.Kaplan-Meier survival analysis of the effects of CRIP1 and STUB1 expression on the prognosis of patients with hepatocellular carcinoma.COX regression analysis was performed to analyze the prognostic factors of hepatocellular carcinoma.Results The positive rate of CRIP1 in cancer tissues of pa-tients with hepatocellular carcinoma was 62.50％(70/112),which was significantly higher than that in adja-cent tissues[7.14％(8/112)],the difference was statistically significant(x2=76.652,P＜0.05).The positive rate of STUB1 in cancer tissues of patients with hepatocellular carcinoma was 26.23％(32/112),significantly lower than that in adjacent tissues[82.14％(92/112)],and the difference was statistically significant(x2=73.284,P＜0.05).The expression of CRIP1 was negatively correlated with STUB1 in cancer tissues(r=-0.678,P＜0.001).There were significant differences in the positive rates of CRIP1 and STUB1 in hepato-cellular carcinoma patients with different TNM stages,histological grades and maximum tumor diameter(P＜0.05).The 3-year cumulative survival rate of CRIP1 positive group was significantly lower than that of CRIP1 negative group,with statistical significance(Log-rank x2=29.601,P＜0.001).The 3-year cumulative survival rate of STUB1 negative group was significantly lower than that of STUB1 positive group,with statistical sig-nificance(Log-rank x2=13.590,P＜0.001).TNM stage Ⅱ-Ⅲ,histological grade Ⅲ,maximum tumor diam-eter＞5 cm,CRIP1 positive and STUB1 negative were independent risk factors for prognosis of hepatocellular carcinoma patients.Conclusion CRIP1 expression is up-regulated and STUB1 expression is down-regulated in hepatocellular carcinoma tissues.The prognosis of patients with hepatocellular carcinoma can be evaluated clinically based on the expression of CRIP1 and STUB1 in hepatocellular carcinoma tissues.
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Objective To investigate the predictive value of serum oncogene[proliferation-related gene(C-myc),transformation gene(N-ras),silk/threonine kinase 1(PLK1),fibroblast growth factor 2(FGF2)]protein levels in patients with hepatitis B associated hepatocellular carcinoma(HCC)after hepatic arterial chemoem-bolization(TACE).Methods A total of 127 patients with hepatitis B-associated hepatocellular carcinoma ad-mitted to a hospital from July 2016 to January 2021 were selected and divided into death group and survival group according to the follow-up results.The serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels were determined by double-antibody sandwich enzyme-linked immunosorbent assay.Univariate and multivari-ate Cox analysis were used to analyze the risk factors of serum oncogene C-myc,N-ras,PLK1 and FGF2 pro-tein levels in patients with hepatitis B-associated hepatocellular carcinoma after TACE.The receiver operating characteristic curve was used to evaluate the prognostic value of the serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels,and the patients were divided into high expression group and low expression group ac-cording to the corresponding cutoff value.Kaplan-Meier survival curve was used to evaluate the prognosis of different serum oncogene C-myc,N-ras,PLK1 and FGF2 protein level.Results Multivariate Cox regression a-nalysis indicated that TNM stage Ⅲ to Ⅳ(HR=2.998,95％CI:1.239-7.257),portal vein metastasis(HR=3.737,95％CI:1.941-7.193),abdominal metastasis(HR=3.482,95％CI:1.709-7.097),Child-Pugh grade B(HR=2.587,95％CI:1.045-6.406),high serum oncogene C-myc protein level(HR=1.224,95％CI:1.090-1.374),high serum oncogene N-ras protein level(HR=1.218,95％CI:1.097-1.353),high serum oncogene PLK1 protein level(HR=1.237,95％CI:1.110-1.379)and high serum oncogene FGF2 protein level(HR=1.141,95％CI:1.060-1.228)were independent risk factors for the prognosis of hepatitis B-asso-ciated hepatocellular carcinoma patients after TACE(all P＜0.05).The overall survival rate of low expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level was significantly higher than that of high expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level,the difference was statistically significant(all P＜0.001).Conclusion Serum oncogene C-myc,N-ras,PLK1,FGF2 protein levels have predic-tive value for the prognosis of patients with HBV-related liver cancer after TACE.
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Objective To investigate the expression and clinical significance of long non-coding RNA(ln-cRNA)MIR100HG in hepatocellular carcinoma tissues,and to verify the regulatory relationship of lncRNA MIR100HG and hsa-miR-2355-3p and its effect on migration and invasion ability of hepatocellular carcinoma cell.Methods Real-time fluorescence quantitative PCR was used to detect the expressions of lncRNA MIR100HG and hsa-miR-2355-3p in cDNA chips;the correlation between the lncRNA MIR100HG relative ex-pression level in hepatocellular carcinoma tissues and clinicopathological parameters as well as prognosis were analyzed,dual luciferase reporter assay was applied to verify the regulatory relationship between lncRNA MIR100HG and hsa-miR-2355-3p,the effects of lncRNA MIR100HG and hsa-miR-2355-3p on the migration and invasion of hepatocellular carcinoma cell line HepG2 were utilized by Transwell assay.Results Compared with the down-regulated expression of hsa-miR-2355-3p in hepatocellular carcinoma tissues,lncRNA MIR100HG was abnormally highly expressed in hepatocellular carcinoma tissues.In hepatocellular carcinoma tissues,lncRNA MIR100HG high-expression group had larger tumor maximum diameter,and were more prone to lymph node metastasis,vascular invasion,and distant tumor metastasis.The higher the level of serum gamma-glutamyl transpeptidase,the higher the TNM stage of tumor and the more inclined to tumor recur-rence.In patients with hepatocellular carcinoma in TNM-stage Ⅰ to Ⅳ,TNM-stage Ⅰ and TNM-stage Ⅱ,the overall survival rate and relapse-free survival rate of patients in the high expression group of lncRNA MIR100HG were significantly lower than those in the low expression group.Multivariate regression analysis showed that abnormally high expression of lncRNA MIR100HG was an independent risk factor for poor prog-nosis in patients with hepatocellular carcinoma.Transwell experiments showed that down-regulation of hsa-miR-2355-3p could reverse lncRNA MIR100HG silencing-mediated inhibition of invasion and migration of hepatocellular carcinoma cell;Dual luciferase reporter experiments indicated that lncRNA MIR100HG may in-teract with hsa-miR-2355-3p physically.Conclusion The abnormally high expression of lncRNA M1R100HG is closely related to the malignant biological behavior of hepatocellular carcinoma,which may promote hepato-cellular carcinoma migration and invasion by mediating hsa-miR-2355-3p.
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Objective To explore the mechanism of the demethylase fat mass and obesity associatal(FTO)gene on the proliferation of human liver cancer cell line HepG2.Methods HepG2 cells were divided into the control group,FTO group(transfected with FTO over-expression plasmid),si-FTO group(transfected with si-FTO)and si-FTO+si-FoxO1 group(simultaneously transfected with si-FTO and si-FoxO1).The expression of FTO in cells was detected by RT-qPCR.Cell proliferation,invasion and apoptosis were examined using CCK-8 assay,Transwell chamber assay and flow cytometry,respectively.Dot blot assay was performed to measure m6 A methylation,and protein expression of FoxO1 in cells was detected by Western blot.Results Analysis of overall survival in liver cancer patients using The Cancer Genome Atlas(TCGA)showed higher expression of FTO associated with shorter survival(P＜0.05).Compared with normal liver cells HL7702,FTO relative expression was significantly increased in human liver cancer cells HepG2(P＜0.05).The relative expression of FTO in si-FTO group cells was lower than that in the control group,while the relative expression of FTO in FTO group was higher than that in the control group(P＜0.05).The relative expression of FTO in the si-FTO+si-FoxO1 group was higher than that in the si-FTO group(P＜0.05).Compared with the Control group,cell viability,count of invasive cells,relative level of m6 A were significantly decreased,while apoptosis rate and protein expression of FoxO1 were significantly increased in the si-FTO group(P＜0.05).Cell viability,count of invasive cells,and relative expression level of m6 A were sig-nificantly higher,while apoptosis rate and protein expression of FoxO1 were significantly lower in the FTO group compared to the Control group(P＜0.05).Compared with the si-FTO group,cell viability,invasive cells and rela-tive level of m6 A were significantly increased,while apoptosis rate and protein expression of FoxO1 were significant-ly decreased in the si-FTO+si-FoxO1 group(P＜0.05).Conclusion High expression of FTO is associated with poor clinical prognosis.Knockdown of the demethylase FTO gene inhibits proliferation and invasion of liver cancer cells and induces their apoptosis.The mechanism is potentially related to the regulation of FoxO1.
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Objective To investigate the relationship between aspartate aminotransferase-platelet ratio index(APRI)and hepatocellular carcinoma(HCC)recurrence after radiofrequency ablation(RFA),and to construct a nomogram model for predicting the prognosis.Methods The clinical data of a total of 204 patients,whose initial diagnosis was HCC and received RFA at the Wujin Hospital Affiliated to Jiangsu University of China between January 2017 and December 2020,were retrospectively analyzed.The optimal cut-off value of APRI was determined using receiver operating characteristic(ROC)curve.Kaplan-Meier curves were plotted to estimate the recurrence-free survival(RFS)of high-APRI group patients and low-APRI group patients.The independent predictors of HCC recurrence after RFA were identified by using univariate and multivariate Cox regression analysis,and significant variables were selected to construct a nomogram model.The predictive ability of the nomogram model for HCC recurrence was evaluated by the consistency index(C-index)and calibration curves.Results The incidence of HCC recurrence after RFA was 57.4%(117/204),the optimal cut-off value of APRI for predicting HCC recurrence was 0.501,and the area under curve(AUC)value was 0.678(95%CI=0.603-0.752).High-APRI group(≥0.501)had 121 patients and low-APRI group(＜0.501)had 83 patients.High APRI index was significantly correlated with low RFS(χ2=12.929,P＜0.01).The univariate and multivariate Cox regression analysis revealed that the number of tumors(HR=1.541,95%CI=1.039-2.286,P=0.031),maximum tumor diameter(HR=1.461,95%CI=1.011-2.112,P=0.044),serum AFP level(HR=2.286,95%CI=1.576-3.318,P＜0.01)and APRI index(HR=1.873,95%CI=1.257-2.790,P=0.002)were the independent risk factors for HCC recurrence.Based on the above four variables,a nomogram model for predicting HCC recurrence after RFA was constructed,the C-index was 0.769(95%CI=0.676-0.862),and the AUC values for 1-,2-,and 3-year RFS prediction were 0.707,0.719,and 0.707,respectively.The calibration curves showed that a good consistency existed between the predicted probability and actual probability.Conclusion The nomogram model based on APRI and tumor biological characteristics has an excellent predictive ability for HCC recurrence after RFA.(J Intervent Radiol,2024,32:38-43)
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Objective To discuss the effect of PI3K-AKT signaling pathway regulated by microRNA-155(miRNA-155)targeted protein tyrosine phosphatase non-receptor type 21(PTPN21)on the proliferation,migration and invasion of hepatocellular carcinoma(HCC)cells.Methods Lentivirus transfection was used to silence the expression of miRNA-155 in human Huh7 HCC cells,and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to detect the silencing effect of miR-155.After obtaining stable cell lines,the cell lines were randomly divided into Blank group(normal Huh7 cells),shNC group(Huh7 cells+empty miR-155 vector),sh-miR-155(Huh7 cells+miR-155 silencing),sh-miR-155+Recilisib group(Huh7 cells+miR-155 silencing+PI3K-AKT agonist),shNC+Recilisib group(Huh7 cells+empty miR-155 vector+PI3K-AKT agonist).Dual luciferase assay was used to determine whether PTPN21 was the downstream of miR-155.The cell proliferation ability of cells in each group was detected by MTT assay.The apoptosis level of each group was tested by flow cytometry.The invasion and migration ability of cells was assessed by Transwell assay.Western blot analysis was used to observe the differences in protein expression of PTPN21,PI3K,P-PI3K,AKT,P-AKT,and apoptosis-related proteins including BAX,BCL-2 and caspase-3 in all groups.Results The expression level of miR-155 in sh-miR-155 group was lower than that in Blank group and shNC group(P＜0.000 1),and the difference in miR-155 expression level between Blank group and shNC group was not statistically significant(P＞0.05).MTT results showed that A values of Huh7 cells at 2,3,4 and 5 day in sh-miR-155 group were lower than those in Blank group and shNC group(P＜0.000 1),while these differences between Blank group and shNC group were not statistically significant(P＞0.05).In sh-miR-155 group the A values at 2,3,4 and 5 day were lower than those in sh-miR-155+Recilisib group and shNC+Recilisib group(P=0.0052 and P＜0.0001,respectively),while the A values at 2,3,4 and 5 day in sh-miR-155+Recilisib were lower than those in shNC+Recilisib group(P＜0.000 1).There was no significant differences in cell migration and number of invasion cells between the Blank group and shNC group(P＞0.05).After activation of PI3K-AKT signaling pathway,the migration and invasion capacity of HCC cells in the shNC+Recilisib group were significantly enhanced when compared with the Blank group(P＜0.000 1).In contrast,the number of migrated and invaded Huh7 cells after miR-155 silencing was significantly lower than that in the Blank group and shNC group(P＜0.000 1)and this phenomenon became reversed by PI3K agonist.Compared with the sh-miR-155 group,in the sh-miR-155+Recilisib group the migration and invasion ability of HCC cells was enhanced(P=0.000 2).Lentiviral transfection of Huh7 human HCC cells to silence miR-155 and downregulate miR-155 inhibiting PTPN21 regulation of the PI3K-AKT signaling pathway,thus inhibiting the invasion,migration and proliferation ability of HCC cells and promoting the apoptosis of HCC cells.Conclusion miR-155 inhibits the migration,invasion and proliferation of HCC cells through targeting PTPN21 regulation of PI3K-AKT signaling pathway.The miR-155 may be a potential therapeutic target for HCC in the future.(J Intervent Radiol,2024,32:44-51)
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Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)
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Objective To develop a nomogram model based on the clinical features and the radiomics texture analysis of multimodal magnetic resonance imaging(MRI),so as to predict the tumor response in patients with advanced hepatocellular carcinoma(HCC)3 months after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 105 patients with advanced HCC,whose diagnosis was pathologically-confirmed at the Suzhou Municipal Ninth People's Hospital between January 2017 and December 2021,were enrolled in this study.The patients were randomly divided into training group(n=63)and verification group(n=42).Before chemotherapy,T1WI,T2WI,dynamic contrast-enhanced(DCE)scan,and diffusion-weighted imaging(DWI)were performed by using a 3.0T MRI scanner.A.K.software was used to extract the texture.Three months after chemotherapy,according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)the patients were divided into response group(n=63)and non-response group(n=42).Results Compared with the response group,in the non-response group the percentage of Child-Pugh grade B and BCLC stage C was obviously higher and the serum alpha fetoprotein(AFP)level was remarkably elevated(P＜0.05).A.K.software extracted 396 MRI texture features,and LASSO regression analysis screened out 6 optimal predictors.The radiation score(Rad-score)was calculated by ROC.The AUC of Rad-score for predicting tumor non-response after TACE by ROC in the training group and verification group were 0.842 and 0.803 respectively.Multivariate logistic regression model analysis showed that AFP≥50 ng/mL(OR=1.568,95%CI=1.234-1.902,P=0.003),Child-Pugh grade B(OR=1.754,95%CI=1.326-2.021,P=0.001),BCLC stage C(OR=1.847,95%CI=1.412-2.232,P=0.001)and Rad-score(OR=2.023,95%CI=1.569-2.457,P＜0.001)were the independent risk factors for tumor non-response.Clinico-radiomics combination had the highest AUC value for predicting tumor non-response.The correction curve showed that the nomogram model had a good agreement.Conclusion The quantitative score of radiomics texture analysis of multimodal MRI has a certain value in predicting tumor non-response in advanced HCC patients 3 months after TACE,and the nomogram model,which is constructed if combined with clinical factors,carries good practical potential.(J Intervent Radiol,2024,32:63-68)
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Hepatocellular carcinoma(HCC)is the fifth most common malignant tumor in the world and it is characterized by clinically insidious onset and high mortality rate.As a preferred treatment method for patients with moderate and advanced HCC,transcatheter arterial chemoembolization(TACE)has many advantages such as reducing tumor load and relieving patient pain,but the selection of the patients who may get benefits from TACE treatment remains a challenging issue.Therefore,it is essential to predict the efficacy of TACE.At present,various methods including clinical laboratory testing,imaging method,genetic-molecular method,etc.have been used to predict the therapeutic efficacy of TACE.Imaging prediction has the advantages of high visualization and strong interpretability,and MRI functional imaging sequence can better demonstrate the details of the lesion.Radiomics,as an emerging imaging field,can complement or even replace tumor biopsy by quantifying the tumor phenotypic variation.This paper aims to make a review concerning the correlation between the imaging radiomics and the prediction of TACE efficacy in patients with HCC,and to discuss whether MRI imaging radiomics can be used as a valid and reproducible method for predicting TACE efficacy for HCC.(J Intervent Radiol,2024,32:90-94)
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Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P＜0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P＜0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P＜0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of＜0.505×10-3 mm2/s and a postoperative D value of＜0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.
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Objective To construct and validate a predictive model based on preoperative inflammatory biomarkers,and to evaluate its ability in predicting the prognosis of patients with unresectable hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 544 patients with HCC,who received TACE as the initial treatment at six medical institutions between January 2007 and December 2020,were retrospectively collected.The patients were divided into training cohort(n=376)and validation cohort(n=168).LASSO algorithm and Cox regression analysis were used to screen out the independent influencing factors and to make modelling.The model was validated based on the discrimination,calibration and clinical applicability,and the Kaplan-Meier risk stratification curves were plotted to determine the prognostic differences between groups.The likelihood ratio chi-square value,R2 value,akaike information criterion(AIC)value,C-index and AUROC value of the model were calculated to determine its accuracy and efficiency.Results The training cohort and validation cohort had 376 participants and 168 participants respectively.Multivariate analysis indicated that BCLC,tumor size,number of tumor lesions,neutrophil and prognostic nutritional index(PNI)were the independent influencing factors for postoperative overall survival(OS),with all P being＜0.05;the BCLC grade,tumor size,number of tumor lesions,NLR,PNI and PS score were the independent influencing factors for progression-free survival(PFS),with all P being＜0.05.The C-indexes of the OS and PFS models were 0.735(95％ CI=0.708-0.762)and 0.736(95％ CI=0.711-0.761)respectively,and the external validation was 0.721(95％ CI=0.680-0.762)and 0.693(95％ CI=0.656-0.730)respectively.Ideal discrimination ability of the nomogram was exhibited in time-dependent C-index,time-dependent ROC,and time-dependent AUC.The calibration curves significantly coincided with the ideal standard lines,indicating that the model had high stability and low over-fitting level.Decision curve analysis revealed that there was a wider range of threshold probabilities and it could augment net benefits.The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically between risk categories(P＜0.000 1).The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically among different risk groups(P＜0.000 1).The likelihood ratio chi-square value,R2 value,AIC value,C-index and AUROC value of the model were better than those of other models commonly used in clinical practice.Conclusion The newly-developed prognostic nomogram based on preoperative inflammatory indicators has excellent accuracy as well as excellent prediction effect in predicting the prognosis of patients with unresectable HCC after receiving TACE,therefore,it can be used as an effective tool for guiding individualized treatment and for predicting prognosis.(J Intervent Radiol,2024,33:245-258)
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Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100％in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P＜0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P＜0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P＜0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P＜0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P＜0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)