Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detecti...Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.展开更多
BACKGROUND Low grade fibromyxoid sarcoma(LGFMS)is a rare and benign mesenchymal tumor with indolent course,most commonly found in young or middle-aged men.The majority of the LGFMSs are located in the trunk and deep s...BACKGROUND Low grade fibromyxoid sarcoma(LGFMS)is a rare and benign mesenchymal tumor with indolent course,most commonly found in young or middle-aged men.The majority of the LGFMSs are located in the trunk and deep soft tissue of the lower extremities.They appear as well circumscribed,although not encapsulated,which often leads to incomplete surgical resection.Despite their seemingly benign appearance,these tumors have aggressive behavior with high metastatic and recurrence rates.Accurate histopathologic examination of the specimen and its immunohistochemical analysis are mandatory for a precise diagnosis.CASE SUMMARY We report a case of a 38 year-old-man who presented with jaundice and upper abdominal discomfort.Multi-detector computed tomography and magnetic resonance imaging showed a large left liver tumor mass,extending to the hepatoduodenal ligament.Left hepatectomy was performed with resection and reconstruction of hepatic artery and preservation of middle hepatic vein.Histopathologic examination confirmed the tumor being a low-grade fibromyxoid sarcoma.Three and a half years after surgery,the patient died after being diagnosed with spine metastasis.CONCLUSION Due to poor response to all modalities of adjuvant treatment,we consider that the focus of treatment should be on surgery as the only option for curing the disease.展开更多
Objective:This study was performed to compare the effect of different time intervals between endoscopic retrograde cholangiopancreatography(ERCP)and early laparoscopic cholecystectomy(LC)on the operation duration,post...Objective:This study was performed to compare the effect of different time intervals between endoscopic retrograde cholangiopancreatography(ERCP)and early laparoscopic cholecystectomy(LC)on the operation duration,postoperative hospitalization,and postoperative complications.Materials and methods:We retrospectively reviewed data for 105 patients with cholecystocholedocholithiasis who underwent ERCP and LC from January 2016 to May 2019.The patients were divided into three groups.In Group A,the interval from ERCP to LC was3 days;in Group B,the interval was 4e6 days;and in Group C,the interval was>6 days.We compared operation duration,blood loss volume,postoperative hospitalization,and rate of biliary complications among the three groups and analyzed the risk factors for postoperative complications.Results:Operation duration differed significantly between Groups A and B(47.5 min vs.60.0 min,p?0.033)and between Groups B and C(60.0 min vs.47.5 min,p?0.033).The median blood loss volume was significantly less in Group A than in Group B(8 ml vs.10 ml,p?0.041),and the postoperative hospitalization and rate of postoperative complications did not differ significantly.Conclusion:The best time for patients with cholecystocholedocholithiasis to undergo LC is 0e3 days after ERCP.If the operation cannot be performed within 3 days,we recommend 6 days after ERCP.展开更多
To the Editor: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) promotes the future liver remnant(FLR) rapid proliferation in the short term, which in turn provides an opportunity for...To the Editor: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) promotes the future liver remnant(FLR) rapid proliferation in the short term, which in turn provides an opportunity for radical surgical resection to hepatocellular carcinoma(HCC) for patients with insufficient FLR [ 1, 2 ].展开更多
BACKGROUND Isolated gallbladder injury(GI)(IGI)directly induced by abdominal trauma is rare.Symptoms,indications,and imaging examinations of IGI are frequently non-specific,posing tremendous diagnostic challenges,whic...BACKGROUND Isolated gallbladder injury(GI)(IGI)directly induced by abdominal trauma is rare.Symptoms,indications,and imaging examinations of IGI are frequently non-specific,posing tremendous diagnostic challenges,which are simple to overlook and may have severe implications.Improving doctors'understanding of gallbladder injury(GI)facilitates early detection and decreases the likelihood of severe consequences,including death.CASE SUMMARY We report a case of IGI caused by blunt violence(after falling from three meters with the umbilicus as the stress point)and performed laparoscopic repair of the gallbladder rupture,which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis.Through extensive medical history and dynamic abdominal ultrasound evaluation,doctors can identify GI early and begin surgery,thereby decreasing the devastating repercussions of delayed diagnosis.CONCLUSION This article aims to improve clinicians'understanding of IGI and propose a method for the diagnosis and treatment of GI.展开更多
Purpose:To explore the safety and clinical efficacy of transcatheter arterial chemoembolization(TACE)combined with simultaneous cone beam computed tomography(CBCT)-guided multipolar microwave ablation(MWA)in the treat...Purpose:To explore the safety and clinical efficacy of transcatheter arterial chemoembolization(TACE)combined with simultaneous cone beam computed tomography(CBCT)-guided multipolar microwave ablation(MWA)in the treatment of massive hepatocellular carcinoma(HCC).Materials and methods:Records of nine patients who underwent TACE combined with simultaneous CBCT-guided multipolar MWA for massive HCC,between January and June 2015,were retrospectively reviewed.Technical success rate,blood levels of liver function indicators,complications,and tumor response one month after treatmentwere investigated.Results:The technical success rate of TACE combined with simultaneous MWA was 100%.The mean procedure time was 195.0 min(range,125-350 min),the mean hospital stay after the treatment was 4.0±1.0 days(range,3-7 days),and no serious complications occurred.Minor complications were experienced by some patients but were relieved after conservative treatment.One month after treatment,enhanced CT revealed a complete response rate of 66.7%(6/9),a partial response rate of 22.2%(2/9),and a stable disease rate of 11.1%(1/9).Mild and reversible injury of liver function occurred in these patients.Conclusion:TACE combined with simultaneous CBCT-guided MWA for massive HCC was feasible and safe,and yielded a high response rate.展开更多
BACKGROUND Liver cancer is one of the most highly malignant cancers,characterized by easy metastasis and chemoradiotherapy resistance.Emerging evidence indicates that long noncoding RNAs(LncRNAs),including Lnc524369,a...BACKGROUND Liver cancer is one of the most highly malignant cancers,characterized by easy metastasis and chemoradiotherapy resistance.Emerging evidence indicates that long noncoding RNAs(LncRNAs),including Lnc524369,are highly involved in the initiation,progression,radioresistance,and chemoresistance of hepatocellular carcinoma(HCC).However,the function of Lnc524369 remains unclear.AIM To explore the function of Lnc524369 in HCC.METHODS To investigate the effect of Lnc524369,tissue from 41 HCC patients were analyzed using CCK8,migration,and invasion assays.Lnc524369 and YWHAZ(also named 14-3-3ζ)mRNA were detected by qPCR,and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues.The Cancer Cell Line Encyclopedia(CCLE)databases,STRING database,Human Protein Atlas database,and the TCGA database were used for bioinformatic analysis.RESULTS Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues.Overexpression of Lnc524369 was associated with the proliferation,migration,and invasion of liver cancer cells.YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer,which could be attenuated by overexpression of Lnc524369.Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.CONCLUSION Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fu...Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.展开更多
Background:Cholangiocarcinoma(CCA)is a diverse group of malignancies arising from the intra-or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome.Extrahepatic cholangiocarcinoma(...Background:Cholangiocarcinoma(CCA)is a diverse group of malignancies arising from the intra-or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome.Extrahepatic cholangiocarcinoma(ECC)accounts for 90%of CCA.However,little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy.Methods:Comprehensive genomic profiling(CGP)was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients.Results:The most frequently altered genes were TP53(68%),KRAS(46%),SMAD4(22%),ARID1A(20%)and CDKN2A(19%).Mutual exclusivity was observed between multiple genes including ARID1A:TP53,KRAS:LRP1B and NF2:TP53.Genetic alterations with potential therapeutic implications were identified in 43%of patients.The top three actionable alterations include CDKN2A(n=11),BRAF(n=5)and ERBB2(n=4).Potentially actionable alterations were mainly enriched in the G1-S transition,homologous recombination repair,MAPK/ERK pathway.Conclusions:This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort,and indicates the potential clinical implications for targeted therapies.展开更多
To the editor,Mucoepidermoid carcinoma(MEC)is a common malignancy of the salivary glands,which account for approximately 30%of all malignant salivary gland neoplasms that originate in both the major and minor glands.1...To the editor,Mucoepidermoid carcinoma(MEC)is a common malignancy of the salivary glands,which account for approximately 30%of all malignant salivary gland neoplasms that originate in both the major and minor glands.1 But it is relatively rare at other organs,extremely rare in the hepatobiliary system.To the best of our knowledge,since primary MEC of the liver was first reported in 1971,2 no more than 20 cases have been reported worldwide.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in the world,with a high likelihood of metastasis and a dismal prognosis.The reprogramming of glucosemetabolism is critical in the developme...Background:Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in the world,with a high likelihood of metastasis and a dismal prognosis.The reprogramming of glucosemetabolism is critical in the development ofHCC.TheWarburg effect has recently been confirmed to occur in a variety of cancers,including HCC.However,little is known about the molecular biological mechanisms underlying the Warburg effect in HCC cells.In this study,we sought to better understand how methyltransferase 5,N6-adenosine(METTL5)controls the development of HCC and theWarburg effect.Methods:In the current study,quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of METTL5 in HCC tissues and cell lines.Several different cell models and animal models were established to determine the role of METTL5 in glucose metabolism reprogramming and the underlying molecularmechanism of HCC.Glutathione-S-transferase pulldown,coimmunoprecipitation,RNA sequencing,non-targeted metabolomics,polysome profiling,and luciferase reporter assays were performed to investigate the molecular mechanisms of METTL5 in HCC cells.Results:We discovered that METTL5 drove glucose metabolic reprogramming to promote the proliferation and metastasis of HCC.Mechanistically,upregulation of METTL5 promoted c-Myc stability and thus activated its downstream glycolytic genes lactate dehydrogenase A(LDHA),enolase 1(ENO1),triosephosphate isomerase 1(TPI1),solute carrier family 2 member 1(SLC2A1),and pyruvate kinase M2(PKM2).The c-Box and ubiquitin binding domain(UBA)regions of ubiquitin specific peptidase 5(USP5)binded to c-Myc protein and inhibited K48-linked polyubiquitination of c-Myc.Further study revealed that METTL5 controled the USP5 translation process,which in turn regulated the ubiquitination of c-Myc.Furthermore,we identified cAMP responsive element binding protein 1(CREB1)/P300 as a critical transcriptional regulator ofMETTL5 that promoted the transcription of METTL5 in HCC.In patient-derived tumor xenograft(PDX)models,adenovirus-mediated knockout of METTL5 had a good antitumor effect and prolonged the survival of PDX-bearing mice.Conclusions:These findings point to a novel mechanism by which CREB1/P300-METTL5-USP5-c-Myc controls abnormal glucose metabolism and promotes tumor growth,suggesting that METTL5 is a potential therapeutic target and prognostic biomarker for HCC.展开更多
Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management strategies.Here,we performed a single-cell multi-omics...Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management strategies.Here,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time points.Validation was performed in two independent cohorts with additional LT patients and healthy controls.Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this process.The intensity of the immune response differs between the ACR and non-ACR patients.Notably,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of ACR.This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.展开更多
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,No.ZNLH201902.
文摘Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.
文摘BACKGROUND Low grade fibromyxoid sarcoma(LGFMS)is a rare and benign mesenchymal tumor with indolent course,most commonly found in young or middle-aged men.The majority of the LGFMSs are located in the trunk and deep soft tissue of the lower extremities.They appear as well circumscribed,although not encapsulated,which often leads to incomplete surgical resection.Despite their seemingly benign appearance,these tumors have aggressive behavior with high metastatic and recurrence rates.Accurate histopathologic examination of the specimen and its immunohistochemical analysis are mandatory for a precise diagnosis.CASE SUMMARY We report a case of a 38 year-old-man who presented with jaundice and upper abdominal discomfort.Multi-detector computed tomography and magnetic resonance imaging showed a large left liver tumor mass,extending to the hepatoduodenal ligament.Left hepatectomy was performed with resection and reconstruction of hepatic artery and preservation of middle hepatic vein.Histopathologic examination confirmed the tumor being a low-grade fibromyxoid sarcoma.Three and a half years after surgery,the patient died after being diagnosed with spine metastasis.CONCLUSION Due to poor response to all modalities of adjuvant treatment,we consider that the focus of treatment should be on surgery as the only option for curing the disease.
基金This study was supported by Foundation Project for Medical Science and Technology of Zhejiang Province(2019ZH022 and 2018KY478).
文摘Objective:This study was performed to compare the effect of different time intervals between endoscopic retrograde cholangiopancreatography(ERCP)and early laparoscopic cholecystectomy(LC)on the operation duration,postoperative hospitalization,and postoperative complications.Materials and methods:We retrospectively reviewed data for 105 patients with cholecystocholedocholithiasis who underwent ERCP and LC from January 2016 to May 2019.The patients were divided into three groups.In Group A,the interval from ERCP to LC was3 days;in Group B,the interval was 4e6 days;and in Group C,the interval was>6 days.We compared operation duration,blood loss volume,postoperative hospitalization,and rate of biliary complications among the three groups and analyzed the risk factors for postoperative complications.Results:Operation duration differed significantly between Groups A and B(47.5 min vs.60.0 min,p?0.033)and between Groups B and C(60.0 min vs.47.5 min,p?0.033).The median blood loss volume was significantly less in Group A than in Group B(8 ml vs.10 ml,p?0.041),and the postoperative hospitalization and rate of postoperative complications did not differ significantly.Conclusion:The best time for patients with cholecystocholedocholithiasis to undergo LC is 0e3 days after ERCP.If the operation cannot be performed within 3 days,we recommend 6 days after ERCP.
基金supported by grants from Zhejiang Medical and Health Science and Technology Plan (2021KY473, 2022RC096 and 2022KY029)the Basic Public Welfare Research Project of Zhe-jiang Province (LGF20H030011)。
文摘To the Editor: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) promotes the future liver remnant(FLR) rapid proliferation in the short term, which in turn provides an opportunity for radical surgical resection to hepatocellular carcinoma(HCC) for patients with insufficient FLR [ 1, 2 ].
文摘BACKGROUND Isolated gallbladder injury(GI)(IGI)directly induced by abdominal trauma is rare.Symptoms,indications,and imaging examinations of IGI are frequently non-specific,posing tremendous diagnostic challenges,which are simple to overlook and may have severe implications.Improving doctors'understanding of gallbladder injury(GI)facilitates early detection and decreases the likelihood of severe consequences,including death.CASE SUMMARY We report a case of IGI caused by blunt violence(after falling from three meters with the umbilicus as the stress point)and performed laparoscopic repair of the gallbladder rupture,which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis.Through extensive medical history and dynamic abdominal ultrasound evaluation,doctors can identify GI early and begin surgery,thereby decreasing the devastating repercussions of delayed diagnosis.CONCLUSION This article aims to improve clinicians'understanding of IGI and propose a method for the diagnosis and treatment of GI.
基金supported by the National Natural Science Foundation of China(No.81771955)Guangzhou Science and Technology Program,key projects of collaborative innovation of health medicine(No201704020228)+1 种基金Guangzhou Science and Technology Program,key projects of collaborative innovation of production,learning and research(No.201704020134)Sun Yat-sen University Clinical Trial 5010Project(No.2016002).
文摘Purpose:To explore the safety and clinical efficacy of transcatheter arterial chemoembolization(TACE)combined with simultaneous cone beam computed tomography(CBCT)-guided multipolar microwave ablation(MWA)in the treatment of massive hepatocellular carcinoma(HCC).Materials and methods:Records of nine patients who underwent TACE combined with simultaneous CBCT-guided multipolar MWA for massive HCC,between January and June 2015,were retrospectively reviewed.Technical success rate,blood levels of liver function indicators,complications,and tumor response one month after treatmentwere investigated.Results:The technical success rate of TACE combined with simultaneous MWA was 100%.The mean procedure time was 195.0 min(range,125-350 min),the mean hospital stay after the treatment was 4.0±1.0 days(range,3-7 days),and no serious complications occurred.Minor complications were experienced by some patients but were relieved after conservative treatment.One month after treatment,enhanced CT revealed a complete response rate of 66.7%(6/9),a partial response rate of 22.2%(2/9),and a stable disease rate of 11.1%(1/9).Mild and reversible injury of liver function occurred in these patients.Conclusion:TACE combined with simultaneous CBCT-guided MWA for massive HCC was feasible and safe,and yielded a high response rate.
基金the Medical and Health Science and Technology Project of Zhejiang Province(No.2021KY043)Chinese Foundation for Hepatitis Prevention and Control-TianQing Liver Disease Research Fund Subject(No.TQGB2020168).
文摘BACKGROUND Liver cancer is one of the most highly malignant cancers,characterized by easy metastasis and chemoradiotherapy resistance.Emerging evidence indicates that long noncoding RNAs(LncRNAs),including Lnc524369,are highly involved in the initiation,progression,radioresistance,and chemoresistance of hepatocellular carcinoma(HCC).However,the function of Lnc524369 remains unclear.AIM To explore the function of Lnc524369 in HCC.METHODS To investigate the effect of Lnc524369,tissue from 41 HCC patients were analyzed using CCK8,migration,and invasion assays.Lnc524369 and YWHAZ(also named 14-3-3ζ)mRNA were detected by qPCR,and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues.The Cancer Cell Line Encyclopedia(CCLE)databases,STRING database,Human Protein Atlas database,and the TCGA database were used for bioinformatic analysis.RESULTS Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues.Overexpression of Lnc524369 was associated with the proliferation,migration,and invasion of liver cancer cells.YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer,which could be attenuated by overexpression of Lnc524369.Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.CONCLUSION Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.
文摘Background:Cholangiocarcinoma(CCA)is a diverse group of malignancies arising from the intra-or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome.Extrahepatic cholangiocarcinoma(ECC)accounts for 90%of CCA.However,little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy.Methods:Comprehensive genomic profiling(CGP)was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients.Results:The most frequently altered genes were TP53(68%),KRAS(46%),SMAD4(22%),ARID1A(20%)and CDKN2A(19%).Mutual exclusivity was observed between multiple genes including ARID1A:TP53,KRAS:LRP1B and NF2:TP53.Genetic alterations with potential therapeutic implications were identified in 43%of patients.The top three actionable alterations include CDKN2A(n=11),BRAF(n=5)and ERBB2(n=4).Potentially actionable alterations were mainly enriched in the G1-S transition,homologous recombination repair,MAPK/ERK pathway.Conclusions:This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort,and indicates the potential clinical implications for targeted therapies.
基金This study was supported by Cancer Research and Trans-lational Platform Project of Zhongnan Hospital of Wuhan University,China(No.ZLYNXM202004)This work was also supported by Translational Medicine and Interdisciplinary Research Joint Fund Project of Zhongnan Hospital of Wuhan University,China(No.ZNJC201918).
文摘To the editor,Mucoepidermoid carcinoma(MEC)is a common malignancy of the salivary glands,which account for approximately 30%of all malignant salivary gland neoplasms that originate in both the major and minor glands.1 But it is relatively rare at other organs,extremely rare in the hepatobiliary system.To the best of our knowledge,since primary MEC of the liver was first reported in 1971,2 no more than 20 cases have been reported worldwide.
基金the Ethics Committee of Zhongnan Hospital ofWuhan University(permit number:KELUN2017082 and KELUN2020100)The tissue samples were obtained with written informed consent from each patient.All animal experiments were approved in accordance with the guidelines of the Animal Ethics and Welfare Committee of Wuhan University of Zhongnan Hospital(permit number:ZN2022005).
文摘Background:Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in the world,with a high likelihood of metastasis and a dismal prognosis.The reprogramming of glucosemetabolism is critical in the development ofHCC.TheWarburg effect has recently been confirmed to occur in a variety of cancers,including HCC.However,little is known about the molecular biological mechanisms underlying the Warburg effect in HCC cells.In this study,we sought to better understand how methyltransferase 5,N6-adenosine(METTL5)controls the development of HCC and theWarburg effect.Methods:In the current study,quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of METTL5 in HCC tissues and cell lines.Several different cell models and animal models were established to determine the role of METTL5 in glucose metabolism reprogramming and the underlying molecularmechanism of HCC.Glutathione-S-transferase pulldown,coimmunoprecipitation,RNA sequencing,non-targeted metabolomics,polysome profiling,and luciferase reporter assays were performed to investigate the molecular mechanisms of METTL5 in HCC cells.Results:We discovered that METTL5 drove glucose metabolic reprogramming to promote the proliferation and metastasis of HCC.Mechanistically,upregulation of METTL5 promoted c-Myc stability and thus activated its downstream glycolytic genes lactate dehydrogenase A(LDHA),enolase 1(ENO1),triosephosphate isomerase 1(TPI1),solute carrier family 2 member 1(SLC2A1),and pyruvate kinase M2(PKM2).The c-Box and ubiquitin binding domain(UBA)regions of ubiquitin specific peptidase 5(USP5)binded to c-Myc protein and inhibited K48-linked polyubiquitination of c-Myc.Further study revealed that METTL5 controled the USP5 translation process,which in turn regulated the ubiquitination of c-Myc.Furthermore,we identified cAMP responsive element binding protein 1(CREB1)/P300 as a critical transcriptional regulator ofMETTL5 that promoted the transcription of METTL5 in HCC.In patient-derived tumor xenograft(PDX)models,adenovirus-mediated knockout of METTL5 had a good antitumor effect and prolonged the survival of PDX-bearing mice.Conclusions:These findings point to a novel mechanism by which CREB1/P300-METTL5-USP5-c-Myc controls abnormal glucose metabolism and promotes tumor growth,suggesting that METTL5 is a potential therapeutic target and prognostic biomarker for HCC.
基金Project supported by the Foundation Project for Medical Science and Technology of Zhejiang Province(Nos.2019ZH022 and 2018KY478)the Zhejiang Province Public Welfare Technology Application Research Project(No.LGF19H180021),China
基金This work received financial support from the National Natural Science Foundation of China(no.82070677 and 82201964)Natural Science and Technology Major Project of the Xiamen(no.3502Z20231034)+1 种基金Natural Science Fund for Distinguished Young Scholars of Fujian Province(no.2023J01310519)Natural Science Foundation of Xiamen(no.3502Z20227283 and 3502Z20227122).
文摘Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management strategies.Here,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time points.Validation was performed in two independent cohorts with additional LT patients and healthy controls.Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this process.The intensity of the immune response differs between the ACR and non-ACR patients.Notably,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of ACR.This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.
