BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarniti...BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate these differences.展开更多
OBJECTIVE Passage-dependent cel ular senescence is a complex process limiting the proliferative lifespan of tumor cells but the mechanism of this process is not understood.METHODS Replicative senescenceof pancreatic c...OBJECTIVE Passage-dependent cel ular senescence is a complex process limiting the proliferative lifespan of tumor cells but the mechanism of this process is not understood.METHODS Replicative senescenceof pancreatic carcinoma-derived PANC-1 cells wasanalyzed.Metabolomics and transcriptomic analyses were performed to find endogenous metabolites changed andassociated genes.Mitochondrial function,cell survival andtumorigenesis of replicative senescent PANC-1 cellswere analyzed.PANC-1 cells were transfected with RNAi CPT1C to specifically knockdown CPT1C expressions,then mitochondrial function,cellular senescence,cell survival and tumorigenesis were investigated.MDA-MB-231,HCT116,A549,MCF7,and He Lacells werealso transfected with si RNA CPT1C and cellular senescence were monitored.RESULTS Replicative senescenceof PANC-1 cells was confirmed.Metabolomic and transcriptomicanalyses revealed that acylcarnitines and their upstream regulator carnitine palmitoyltransferase 1C(CPT1C),an enzyme that catalyzes the initiating step of fatty acidβ-oxidation,were markedly decreased in senescent PANC-1 cells.Furthermore,low CPT1C expression caused abnormal energy metabolism and mitochondrial dysfunction of PANC-1 cells,resulting in decreased cell survival and a suppressed tumorigenesis.Most importantly,loss of CPT1C triggered mitochondrial dysfunction,leading to senescence-like growth suppression and cellular senescence,suppressed cell survival under metabolic stress,and lower tumorigenesis in a mouse xenograft model.Silencing of CPT1C also induced cellular senescence in five other tumor cell lines.CONCLUSION Low CPT1C expression is a novel biomarker and key regulator of cellular senescence in tumor cell lines.Inhibition of CPT1C may be a new cancer therapeutic target impacting cellular senescence and tumorigenesis through modulation of mitochondrial function.展开更多
文摘BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate these differences.
文摘OBJECTIVE Passage-dependent cel ular senescence is a complex process limiting the proliferative lifespan of tumor cells but the mechanism of this process is not understood.METHODS Replicative senescenceof pancreatic carcinoma-derived PANC-1 cells wasanalyzed.Metabolomics and transcriptomic analyses were performed to find endogenous metabolites changed andassociated genes.Mitochondrial function,cell survival andtumorigenesis of replicative senescent PANC-1 cellswere analyzed.PANC-1 cells were transfected with RNAi CPT1C to specifically knockdown CPT1C expressions,then mitochondrial function,cellular senescence,cell survival and tumorigenesis were investigated.MDA-MB-231,HCT116,A549,MCF7,and He Lacells werealso transfected with si RNA CPT1C and cellular senescence were monitored.RESULTS Replicative senescenceof PANC-1 cells was confirmed.Metabolomic and transcriptomicanalyses revealed that acylcarnitines and their upstream regulator carnitine palmitoyltransferase 1C(CPT1C),an enzyme that catalyzes the initiating step of fatty acidβ-oxidation,were markedly decreased in senescent PANC-1 cells.Furthermore,low CPT1C expression caused abnormal energy metabolism and mitochondrial dysfunction of PANC-1 cells,resulting in decreased cell survival and a suppressed tumorigenesis.Most importantly,loss of CPT1C triggered mitochondrial dysfunction,leading to senescence-like growth suppression and cellular senescence,suppressed cell survival under metabolic stress,and lower tumorigenesis in a mouse xenograft model.Silencing of CPT1C also induced cellular senescence in five other tumor cell lines.CONCLUSION Low CPT1C expression is a novel biomarker and key regulator of cellular senescence in tumor cell lines.Inhibition of CPT1C may be a new cancer therapeutic target impacting cellular senescence and tumorigenesis through modulation of mitochondrial function.
