Service d'Hépatologie et Université Paris 13, Hôpital Jean Verdier, AP-HP, Bondy, France.
Clin Cancer Res. 2012 Dec 15;18(24):6714-22. doi: 10.1158/1078-0432.CCR-12-1099. Epub 2012 Nov 7.
Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC).
The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components.
The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up.
Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis.
代谢组学使用多参数分析技术描绘生物系统中的代谢变化。本研究评估了来自伴有和不伴有肝细胞癌（HCC）的肝硬化患者的血清代谢组谱，这些血清是通过质子核磁共振（NMR）光谱法获得的。
该研究纳入了 154 例连续的经活检证实的代偿性酒精性肝硬化患者。其中，93 例为无 HCC 的肝硬化患者，28 例为符合米兰标准且有根治性治疗适应证的活检证实 HCC 患者（小 HCC），33 例为超出米兰标准的 HCC 患者（大 HCC）。在 500 MHz 下采集质子谱。建立正交偏最小二乘[正交投影到潜变量结构（OPLS）]分析模型，以区分大 HCC 谱和肝硬化谱。使用先前构建的 OPLS 判别成分对小 HCC 谱进行二次投影。
OPLS 模型显示了肝硬化和大 HCC 谱之间的区分。与大 HCC 显著相关的代谢物为谷氨酸、醋酸盐和 N-乙酰糖蛋白，而与肝硬化相关的代谢物为脂质和谷氨酰胺。将小 HCC 样本投影到 OPLS 模型中，在大 HCC 和肝硬化样本之间显示出不均匀的分布。具有类似于大 HCC 组代谢组学特征的小 HCC 患者在随访期间复发或死亡的发生率更高。
基于血清 NMR 的代谢组学鉴定了可能是肝硬化大 HCC 特异性的代谢指纹。从代谢组学的角度来看，一些有根治性治疗适应证的小 HCC 患者似乎表现为晚期癌症患者。进一步前瞻性研究这些患者以确定预后较差的亚组将是有用的。
