Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma.
Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma.
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DOI：
10.3390/cancers13010088
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发表时间：
2020-12-30
期刊：
影响因子：
5.2
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Ismail IT;Elfert A;Helal M;Salama I;El-Said H;Fiehn O
肝细胞癌（HCC）预后差。我们通过比较健康志愿者与慢性肝病（CLD）患者以及病毒感染引起的HCC患者来研究血脂。我们对比了我们在HCC患者的肝肿瘤和非肿瘤组织样本中的血脂变化。在血液中，与健康志愿者相比，CLD患者中大多数脂质物质的水平升高。这一趋势在HCC与CLD患者中大多逆转。在肝肿瘤组织中，许多脂质的水平与配对的非肿瘤肝组织相比降低。脂质水平的差异进一步定义的脂肪酰基链的饱和度的变化。一些脂质，包括游离脂肪酸，饱和溶血磷脂酰胆碱和饱和甘油三酯，显示出从健康对照到CLD和HCC患者的血液中的过渡的连续趋势。对于HCC患者，磷脂酰甘油酯在血液和组织中显示出类似的变化。肝细胞癌（HCC）是一个世界性的健康问题。HCC患者在诊断后两年内死亡率为50%。为了更好地理解脂质代谢水平的分子发病机制，从切除的人HCC组织及其配对的非肿瘤肝组织（n = 46）获得非靶向UPLC MS-QTOF脂质组学数据。将相同HCC受试者（n = 23）的血液样品与慢性肝病（CLD）（n = 15）和健康对照（n = 15）血液样品进行比较。参与者是从埃及国家肝脏研究所招募的。脂质组学数据产生了604种经鉴定的脂质，这些脂质被分为六个超类。发现三个研究组之间的524项血脂存在显著差异（p < 0.05和qFDR p < 0.1）。与健康对照受试者相比，在CLD患者的血液中，几乎所有的脂质类别都显著上调。在CLD患者中，三酰甘油酯被发现是qFDR p = 1.3 × 10 - 56时上调最显著的脂质类别，其次是磷脂酰胆碱（qFDR p = 3.3 × 10 - 51）和缩醛磷脂（qFDR p = 1.8 × 10-46）。相反，几乎所有的血脂在HCC患者中与CLD患者相比显著下调，并且在HCC组织中与非肿瘤肝组织相比显著下调。发现神经酰胺是最重要的脂质类别（qFDR p = 1 × 10−14），其次是磷脂酰甘油（qFDR p = 3 × 10−9）、磷脂酰胆碱和缩醛磷脂。尽管存在这些主要差异，但健康对照、CLD和HCC患者之间的转变也存在共同趋势。在血液中，几种主要是饱和的三酰甘油酯显示出向HCC的轨迹持续增加，伴随着饱和游离脂肪酸和饱和溶血磷脂酰胆碱水平的降低。相比之下，在HCC组织和血液比较中发现的脂质变化的最大重叠是磷脂酰甘油和鞘脂水平降低。这项研究强调了HCC肿瘤对循环脂质的具体影响。这些数据可用于靶向脂质代谢，以在病毒相关CLD病因学背景下预防、早期检测和治疗HCC。
Hepatocellular carcinoma (HCC) has poor prognosis. We studied blood lipids by comparing healthy volunteers to patients with chronic liver disease (CLD), and to patients with HCC caused by viral infections. We contrasted our findings in blood to lipid alterations in liver tumor and nontumor tissue samples from HCC patients. In blood, most lipid species were found at increased levels in CLD patients compared to healthy volunteers. This trend was mostly reversed in HCC versus CLD patients. In liver tumor tissues, levels of many lipids were decreased compared to paired nontumor liver tissues. Differences in lipid levels were further defined by alterations in the degree of saturation in the fatty acyl chains. Some lipids, including free fatty acids, saturated lysophosphatidylcholines and saturated triacylglycerides, showed a continuous trend in the transition from the blood of healthy controls to CLD and HCC patients. For HCC patients, phosphatidylglycerides showed similar alterations in both blood and tissues. Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS—QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p < 0.05 and qFDR p < 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 × 10−56, followed by phosphatidylcholines at qFDR p = 3.3 × 10−51 and plasmalogens at qFDR p = 1.8 × 10-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 × 10−14) followed by phosphatidylglycerols (qFDR p = 3 × 10−9), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology.
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影响因子：
3.8
作者：
Hanyu, Takaaki;Nagahashi, Masayuki;Wakai, Toshifumi
通讯作者：
Wakai, Toshifumi
影响因子：
5.2
作者：
Ismail, Israa T.;Fiehn, Oliver;El-Said, Hala
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影响因子：
39.3
作者：
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通讯作者：
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影响因子：
7.4
作者：
DeFelice BC;Mehta SS;Samra S;Čajka T;Wancewicz B;Fahrmann JF;Fiehn O
通讯作者：
Fiehn O
影响因子：
12.3
作者：
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通讯作者：
Fiehn O