Diagnostic Value of Systemic Cholesteryl Ester/Free Cholesterol Ratio in Hepatocellular Carcinoma

Krautbauer, Sabrina; Weiss, Thomas S.; Wiest, Reiner; Schacherer, Doris; Liebisch, Gerhard; Buechler, Christa

doi:10.21873/anticanres.11721

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…None of the studies reported the differences in complete PL profiles between HCC and BHT samples. Few investigators performed partial PL profiles on plasma samples from HCC patients [ 6 , 13 , 14 ]. They found that several PL species were increased or decreased in plasma samples from HCC patients as compared to plasma samples from human subjects without cancers.…”

Section: Discussionmentioning

confidence: 99%

Distribution and clinical relevance of phospholipids in hepatocellular carcinoma

et al. 2020

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Background Hepatocellular carcinoma (HCC) is the most common liver cancer and featured with prominent disparity in incidence and mortality rate between male and female. It remains unclear whether alterations of phospholipids (PL) in hepatic tissues contribute to the pathogenesis, progression, and disparity of HCC. Methods Using electrospray ionization mass spectrometry (ESI-MS), PL profiles including 320 individual phospholipid species in 13 PL classes were determined in paired samples from HCC and adjacent benign hepatic tissues (BHT). Results (1) Concentrations of PLs in most of individual species, in subgroups and in total were decreased in HCC than in BHT in all studied population; (2) the number of individual PL species significantly different between HCC and BHT, and the number of PLs in six subgroups and in total decreased in HCC were more in male population than in female population; (3) panels of PL parameters (more in male population than in female population) were identified as biomarkers in differentiation of HCC from BHT, and in the prediction of pathological grade and clinical stage of HCC with high sensitivity, specificity, and accuracy. Conclusion It is concluded that alterations of PLs in hepatic tissues play important roles in pathogenesis, progression, and gender disparity of HCC.

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Section: Discussionmentioning

confidence: 99%

Distribution and clinical relevance of phospholipids in hepatocellular carcinoma

et al. 2020

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“…These data, together with a recent report that showed that HCC tissues are characterized by reduced Cer and increased SM compared with ANLTs and that impaired SMase's activity might be an underlying mechanism of HCC development [12], indicate that low NSMase1 expression might be involved in HCC progression. Cer is regarded as a tumor suppressor, and Cer is diminished in HCC tissues [29]. However, SM has been reported to be downregulated in serum of HCC patients compared with healthy controls [30].…”

Section: Discussionmentioning

confidence: 99%

Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

et al. 2018

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Neutral sphingomyelinase 1 (NSMase1) mediates caspase-3 activation and apoptosis. However, the role of NSMase1, especially exosome-borne NSMase1 in hepatocellular carcinoma (HCC), remains unclear. We report that NSMase1, which converts sphingomyelin (SM) to ceramide, was significantly downregulated in HCC tissues. Low NSMase1 expression predicted poor long-term survival of HCC patients. NSMase1 downregulation in HCC resulted in increased SM and reduced ceramide (Cer) that led to an increased SM/Cer ratio. Interestingly, NSMase1 and NSMase activity were also decreased in exosomes isolated from HCC tissues and cell lines. Furthermore, NSMase activity increased in exosomes isolated from the culture medium of L02 cells transfected with pEGFP-C3-NSMase1 (NSMase1-Exo). NSMase1-Exo suppressed HCC cell growth and induced apoptosis via reduction of the SM/Cer ratio. Thus, NSMase1 in exosomes inhibits HCC growth by decreasing the SM/Cer ratio.

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“…Therefore, both forms of cholesterol play an active part in metabolic pathways. In addition, the CE/free cholesterol ratio has been shown to be altered in some diseases, such as hepatocellular carcinoma [ 36 ] or cardiovascular disease [ 27 ]. Moreover, the molecular composition of CE species and changes in specific CE species may be related to the development of other diseases such as cystic fibrosis, Huntington disease, neurological disorders like multiple sclerosis or Alzheimer’s disease [ 12 , 46 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters

et al. 2022

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Background Inhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foam macrophage formation. Results The histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of total and foam macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages also significantly was increased. The gene and protein expression of a cholesterol transporter CD36, which is associated with lipid metabolism, was altered in the liver. The amount of selected cholesteryl esters (CE 16:0, CE 18:1, CE 20:4, CE 22:6) in liver tissue was decreased after subchronic PbO NP inhalation, while total and free cholesterol in liver tissue was slightly increased. Gene and protein expression of phospholipase PLCβ1 and receptor CD36 in human hepatocytes were affected also in in vitro experiments after acute PbO NP exposure. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in its interstitial tissues. Conclusion Our study revealed the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and yet uncovered processes, which can contribute to steatosis in liver after metal nanoparticles exposure. Graphical abstract

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Diagnostic Value of Systemic Cholesteryl Ester/Free Cholesterol Ratio in Hepatocellular Carcinoma

Abstract: The cholesteryl ester/free cholesterol ratio is comparable in controls and patients with cirrhosis, but is specifically increased in patients with HCC.

Cited by 5 publications

References 30 publications

Distribution and clinical relevance of phospholipids in hepatocellular carcinoma

Distribution and clinical relevance of phospholipids in hepatocellular carcinoma

Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide

Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters

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