BACKGROUND Radical resection remains an effective strategy for patients with hepatocellular carcinoma(HCC).Unfortunately,the postoperative early recurrence(recurrence within 2 years)rate is still high.AIM To develop a...BACKGROUND Radical resection remains an effective strategy for patients with hepatocellular carcinoma(HCC).Unfortunately,the postoperative early recurrence(recurrence within 2 years)rate is still high.AIM To develop a radiomics model based on preoperative contrast-enhanced computed tomography(CECT)to evaluate early recurrence in HCC patients with a single tumour.METHODS We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection.First,the features from the portal venous and arterial phases of CECT were extracted based on the region of interest,and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model(LASSO Cox)to determine radiomics scores for each patient.Then,the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression.Finally,we evaluated the prediction performance of this model by multiple methods.RESULTS A total of 1915 radiomics features were extracted from CECT images,and 31 of them were used to determine the radiomics scores,which showed a significant difference between the early recurrence and nonearly recurrence groups.Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alphafetoprotein were independent indicators,and they were used to develop a combined model to predict early recurrence.The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74,respectively,while the C-indices were 0.712 and 0.674,respectively.The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities.Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences.CONCLUSION The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.展开更多
BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and c...BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.METHODS With liver biopsy as the gold standard,we established a new index,[alkaline phosphatase(U/L)+gamma-glutamyl transpeptidase(U/L)/platelet(109/L)(AGPR)],to predict liver fibrosis and cirrhosis.In addition,we compared the area under the receiver operating characteristic curve(AUROC)of AGPR,gammaglutamyl transpeptidase to platelet ratio,aspartate transaminase to platelet ratio index,and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage(P<0.001).In the training cohort,the AUROC of AGPR was 0.83(95%CI:0.78-0.87)for predicting fibrosis(≥F2),0.84(95%CI:0.79-0.88)for predicting extensive fibrosis(≥F3),and 0.87(95%CI:0.83-0.91)for predicting cirrhosis(F4).In the validation cohort,the AUROCs of AGPR to predict≥F2,≥F3 and F4 were 0.83(95%CI:0.77-0.88),0.83(95%CI:0.77-0.89),and 0.84(95%CI:0.78-0.89),respectively.CONCLUSION The AGPR index should become a new,simple,accurate,and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.展开更多
Tumor-specific neoantigens,which are expressed on tumor cells,can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression.Among tumor immunotherapies,neoantigen vaccines are in early human...Tumor-specific neoantigens,which are expressed on tumor cells,can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression.Among tumor immunotherapies,neoantigen vaccines are in early human clinical trials and have demonstrated substantial efficiency.Compared with more neoantigens in melanoma,the paucity and inefficient identification of effective neoantigens in hepatocellular carcinoma(HCC)remain enormous challenges in effectively treating this malignancy.In this review,we highlight the current development of HCC neoantigens in its generation,screening,and identification.We also discuss the possibility that there are more effective neoantigens in hepatitis B virus(HBV)-related HCC than in non-HBV-related HCC.In addition,since HCC is an immunosuppressive tumor,strategies that reverse immunosuppression and enhance the immune response should be considered for the practical exploitation of HCC neoantigens.In summary,this review offers some strategies to solve existing problems in HCC neoantigen research and provide further insights for immunotherapy.展开更多
Background:Our previous studies have shown that regulatory factor X5(RFX5),a classical transcription regulator of MHCⅡ genes,was obviously overexpressed in hepatocellular carcinoma(HCC)tumors.However,the role of RFX5...Background:Our previous studies have shown that regulatory factor X5(RFX5),a classical transcription regulator of MHCⅡ genes,was obviously overexpressed in hepatocellular carcinoma(HCC)tumors.However,the role of RFX5 in the carcinogenesis and progress of HCC remains unknown.This study aimed to reveal its biological significance and the underlying mechanism in HCC.Methods:RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database.The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR7Cas9 system in HCC cell lines.The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay.The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta(YWHAQ)in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment.The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis.Moreover,apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.Results:RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues.The mRNA expression level of RFX5 was significantly correlated with its DNA copy number(r=0.4,P<0.001).Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells.Further study identified YWHAQ,namely 14-3-3 tau,as a key downstream transcriptional target gene of RFX5,which was tightly regulated by RFX5 in HCC.Moreover,overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown.In addition,overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC.These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC.Notably,RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.Conclusion:RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.展开更多
基金National Natural Science Foundation of China,No.81773148Natural Science Foundation of Guangxi,No.2018GXNSFDA138001+3 种基金Program of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,No.Z20210706Guangxi Medical and Healthcare Appropriate Technology Development and Promotion and Application Projects,No.S2022132Guangxi Natural Science Foundation,No.2022JJA140009Guangxi Zhuang Autonomous Region Health and Family Planning Commission Self-funded of Scientific Research Project,No.Z20170812.
文摘BACKGROUND Radical resection remains an effective strategy for patients with hepatocellular carcinoma(HCC).Unfortunately,the postoperative early recurrence(recurrence within 2 years)rate is still high.AIM To develop a radiomics model based on preoperative contrast-enhanced computed tomography(CECT)to evaluate early recurrence in HCC patients with a single tumour.METHODS We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection.First,the features from the portal venous and arterial phases of CECT were extracted based on the region of interest,and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model(LASSO Cox)to determine radiomics scores for each patient.Then,the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression.Finally,we evaluated the prediction performance of this model by multiple methods.RESULTS A total of 1915 radiomics features were extracted from CECT images,and 31 of them were used to determine the radiomics scores,which showed a significant difference between the early recurrence and nonearly recurrence groups.Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alphafetoprotein were independent indicators,and they were used to develop a combined model to predict early recurrence.The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74,respectively,while the C-indices were 0.712 and 0.674,respectively.The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities.Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences.CONCLUSION The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.
基金Supported by the National Natural Science Foundation of China,No.81372163the Natural Science Foundation of Guangxi,No.2018GXNSFDA138001+2 种基金the Science and Technology Planning Project of Guilin,No.20190218-1the Opening Project of Key laboratory of High-Incidence-Tumor Prevention&Treatment(Guangxi Medical University),Ministry of Education,No.GKE-KF202101the Program of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,No.Z20210706 and No.Z20190665。
文摘BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.METHODS With liver biopsy as the gold standard,we established a new index,[alkaline phosphatase(U/L)+gamma-glutamyl transpeptidase(U/L)/platelet(109/L)(AGPR)],to predict liver fibrosis and cirrhosis.In addition,we compared the area under the receiver operating characteristic curve(AUROC)of AGPR,gammaglutamyl transpeptidase to platelet ratio,aspartate transaminase to platelet ratio index,and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage(P<0.001).In the training cohort,the AUROC of AGPR was 0.83(95%CI:0.78-0.87)for predicting fibrosis(≥F2),0.84(95%CI:0.79-0.88)for predicting extensive fibrosis(≥F3),and 0.87(95%CI:0.83-0.91)for predicting cirrhosis(F4).In the validation cohort,the AUROCs of AGPR to predict≥F2,≥F3 and F4 were 0.83(95%CI:0.77-0.88),0.83(95%CI:0.77-0.89),and 0.84(95%CI:0.78-0.89),respectively.CONCLUSION The AGPR index should become a new,simple,accurate,and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.
基金National Key Sci-Tech Special Project of China,No.2018ZX10302207。
文摘Tumor-specific neoantigens,which are expressed on tumor cells,can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression.Among tumor immunotherapies,neoantigen vaccines are in early human clinical trials and have demonstrated substantial efficiency.Compared with more neoantigens in melanoma,the paucity and inefficient identification of effective neoantigens in hepatocellular carcinoma(HCC)remain enormous challenges in effectively treating this malignancy.In this review,we highlight the current development of HCC neoantigens in its generation,screening,and identification.We also discuss the possibility that there are more effective neoantigens in hepatitis B virus(HBV)-related HCC than in non-HBV-related HCC.In addition,since HCC is an immunosuppressive tumor,strategies that reverse immunosuppression and enhance the immune response should be considered for the practical exploitation of HCC neoantigens.In summary,this review offers some strategies to solve existing problems in HCC neoantigen research and provide further insights for immunotherapy.
基金grants from the National Natural Science Foundation of China(No.81201569 and No.81541151)the Beijing Natural Science Foundation(No.7132186)the National Key Sci-Tech Special Project of China(No.2018ZX10302207,No.2017ZX10203202).
文摘Background:Our previous studies have shown that regulatory factor X5(RFX5),a classical transcription regulator of MHCⅡ genes,was obviously overexpressed in hepatocellular carcinoma(HCC)tumors.However,the role of RFX5 in the carcinogenesis and progress of HCC remains unknown.This study aimed to reveal its biological significance and the underlying mechanism in HCC.Methods:RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database.The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR7Cas9 system in HCC cell lines.The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay.The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta(YWHAQ)in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment.The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis.Moreover,apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.Results:RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues.The mRNA expression level of RFX5 was significantly correlated with its DNA copy number(r=0.4,P<0.001).Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells.Further study identified YWHAQ,namely 14-3-3 tau,as a key downstream transcriptional target gene of RFX5,which was tightly regulated by RFX5 in HCC.Moreover,overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown.In addition,overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC.These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC.Notably,RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.Conclusion:RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.
