日前,，中科院大連化學物理研究所研究員許國旺團隊與上海東方肝膽醫(yī)院王紅陽院士課題組合作，將基于液相色譜—質譜用于肝癌組織非靶標代謝組學研究并取得了重要進展,，相關成果在美國《癌癥研究》上在線發(fā)表,。
肝癌在臨床上早診困難，治療預后效果差,。深入了解肝癌的發(fā)病機理對制定治療方案,、改善治療效果、降低肝癌發(fā)病率和死亡率都有重要的意義,。組織代謝組學方法是研究肝癌代謝異常的有力工具,，可為肝癌發(fā)病機理的闡明和新型診斷標志物的發(fā)現提供依據。
研究人員基于超高效液相色譜—高分辨質譜分析平臺,，對50例肝癌患者的癌組織,、癌旁近端組織和遠端組織進行了非靶標代謝譜分析，結合多變量數據處理方法和生物信息學技術,，從整體層面闡明了肝癌微環(huán)境的代謝紊亂狀況,。結果表明，肝癌患者出現了大量的代謝異常,，主要包括糖酵解加速,、三羧酸循環(huán)抑制、糖異生和β-氧化加快以進一步提供能量,、脂肪酸代謝相關的Δ-12脫氫酶活性顯著下調,。此外，谷胱甘肽等抗氧化分子水平增高,，炎癥相關的多不飽和脂肪酸和磷脂酶A2水平下降,。
研究人員將組織中發(fā)現的差異代謝物在298例慢性肝炎、肝硬化和肝癌病人血清樣本中檢測,，發(fā)現甜菜堿和丙酰肉堿聯合對原發(fā)性肝癌有良好的診斷能力,。通過另一批血清樣本的外部驗證，進一步證實了上述兩種代謝物在肝癌中的診斷潛力,，與肝癌標志物甲胎蛋白有很好的互補性,。(生物谷Bioon.com)
生物谷推薦的英文摘要
Cancer Research doi: 10.1158/0008-5472.CAN-13-0308
Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics
Qiang Huang, Yexiong Tan, Peiyuan Yin, Guozhu Ye, Peng Gao, Xin Lu, Hongyang Wang, and Guowang Xu
Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and β-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein.
