1.Prognosis prediction model for hepatocellular carcinoma based on autophagy related genes.
Wei HUANG ; Ning HAN ; Lingyao DU ; Dan CAO ; Hong TANG
Journal of Biomedical Engineering 2022;39(1):120-127
Autophagy is a programmed cell degradation process that is involved in a variety of physiological and pathological processes including malignant tumors. Abnormal induction of autophagy plays a key role in the development of hepatocellular carcinoma (HCC). We established a prognosis prediction model for hepatocellular carcinoma based on autophagy related genes. Two hundred and four differentially expressed autophagy related genes and basic information and clinical characteristics of 377 registered hepatocellular carcinoma patients were retrieved from the cancer genome atlas database. Cox risk regression analysis was used to identify autophagy-related genes associated with survival, and a prognostic model was constructed based on this. A total of 64 differentially expressed autophagy related genes were identified in hepatocellular carcinoma patients. Five risk factors related to the prognosis of hepatocellular carcinoma patients were determined by univariate and multivariate Cox regression analysis, including TMEM74, BIRC5, SQSTM1, CAPN10 and HSPB8. Age, gender, tumor grade and stage, and risk score were included as variables in multivariate Cox regression analysis. The results showed that risk score was an independent prognostic risk factor for patients with hepatocellular carcinoma ( HR = 1.475, 95% CI = 1.280-1.699, P < 0.001). In addition, the area under the curve of the prognostic risk model was 0.739, indicating that the model had a high accuracy in predicting the prognosis of hepatocellular carcinoma. The results suggest that the new prognostic risk model for hepatocellular carcinoma, established by combining the molecular characteristics and clinical parameters of patients, can effectively predict the prognosis of patients.
Autophagy/genetics*
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Biomarkers, Tumor/genetics*
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Carcinoma, Hepatocellular/pathology*
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Humans
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Liver Neoplasms/pathology*
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Membrane Proteins/genetics*
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Prognosis
4.hTERT single nucleotide polymorphism is associated with increased risks of hepatocellular carcinoma and tumor metastasis.
Jin DONG ; Ling WANG ; Ya-ping TIAN ; Yue GUO ; Hong-ying LIU
Journal of Southern Medical University 2011;31(1):49-52
OBJECTIVETo investigate the effect of hTERT single nucleotide polymorphisms on the development and metastasis of hepatocellular carcinoma.
METHODSA total of 290 male patients were divided into hepatitis-induced primary hepatocellular carcinoma (HCC) group (n%162), metastatic HCC group (n%22), and control group (n%106). hTERT gene was amplified and hTERT single nucleotide polymorphisms (SNPs) were tested in these subjects.
RESULTSSignificant differences were found in rs2853690 and rs10069690 distribution, but the difference in rs6554743 remained uncertain. The C and T alleles of rs10069690 and rs6554743 showed significant differences between the 3 groups; the carriers of non-T allele of rs10069690 had higher frequencies in both primary and metastatic HCC groups.
CONCLUSIONSome of the polymorphisms of hTERT may increase the risks of development and metastasis of hepatocellular carcinoma.
Carcinoma, Hepatocellular ; genetics ; pathology ; Humans ; Liver Neoplasms ; genetics ; pathology ; Male ; Neoplasm Metastasis ; genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Telomerase ; genetics
7.Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration.
Jia Jia CAI ; Min Ting LIANG ; Wan Qing LI ; Wei Yun ZHANG ; Xiao LI ; Zhao Hui SUN
Chinese Journal of Preventive Medicine 2023;57(7):1068-1074
To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.
Humans
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Carcinoma, Hepatocellular/pathology*
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Ferroptosis
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Liver Neoplasms/pathology*
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Peroxisome Proliferator-Activated Receptors/genetics*
8.Triton X-100 induces apoptosis in human hepatoma cell lines.
Ju Mi AHN ; Se Jong KIM ; Hoguen KIM ; Chanil PARK ; Won Ho KIM ; Jeon Han PARK
Yonsei Medical Journal 1997;38(1):52-59
The detergent Triton X-100 was used to establish a model for apoptosis in hepatoma cell lines. The electrophoresis of DNA extracted from 0.01% Triton X-100 treated hepatoma cell lines showed DNA ladder formation, a hallmark of apoptosis. The DNA fragmentation appeared within less than 60 min of the Triton X-100 treatment. Chromatin condensation and apoptotic bodies were observed by hematoxylin and eosin (H & E) stain, and fragmented nucleosome was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) test. Apoptosis was semi-quantitated by measuring the lactate dehydrogenase (LDH) level for cytotoxity. It was found that apoptosis had been induced in more than 90% of the cells treated with Triton X-100 for 150 min. These data show that Triton X-100 efficiently induces the apoptotic cell death in hepatoma cell lines.
Apoptosis*
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Carcinoma, Hepatocellular/pathology*
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Carcinoma, Hepatocellular/genetics
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DNA Fragmentation
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Detergents/pharmacology*
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Human
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Liver Neoplasms/pathology*
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Liver Neoplasms/genetics
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Octoxynol/pharmacology*
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Tumor Cells, Cultured/drug effects