Danilova Olga V, Dumont Larry J, Levy Norman B, Lansigan Frederick, Kinlaw William B, Danilov Alexey V, Kaur Prabhjot
Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
J Hematop. 2013 Mar;6(1):11-18. doi: 10.1007/s12308-012-0166-4.
Diffuse large B-cell lymphoma is the most common lymphoid malignancy, as it accounts for approximately one third of all patient cases of non-Hodgkin's lymphoma. Patients with diffuse large B-cell lymphoma have markedly different treatment outcomes, suggesting a need for reliable prognostic factors and novel therapeutic approaches. De novo fatty acid synthesis is an important metabolic driver of tumor in multiple malignancies. In this retrospective study, we analyzed expression of fatty acid synthase (a key enzyme in de novo fatty acid synthesis), Spot 14 (thyroid hormone responsive Spot 14, a nuclear protein that promotes expression of genes involved in fatty acid synthesis), and CD36 (the cell surface channel for exogenous fatty acid uptake) in patients with diffuse large B-cell lymphoma and their clinical significance. We observed that overexpression of fatty acid synthase is negatively associated with overall survival (=0.001) and progression-free period (=0.004) in patients with diffuse large B-cell lymphoma. Multivariate analysis showed that fatty acid synthase overexpression is an independent prognostic marker of aggressive clinical course. For the first time, we report CD36 as an independent protective factor in patients treated with rituximab. Thus, fatty acid synthase and CD36 expression may serve as prognostic markers to predict response to treatment and survival in diffuse large B-cell lymphoma patients. Fatty acid synthase may also be a potential therapeutic target in lymphoid malignancies.
弥漫性大B细胞淋巴瘤是最常见的淋巴系统恶性肿瘤，约占所有非霍奇金淋巴瘤患者病例的三分之一。弥漫性大B细胞淋巴瘤患者的治疗结果差异显著，这表明需要可靠的预后因素和新的治疗方法。从头脂肪酸合成是多种恶性肿瘤中肿瘤的重要代谢驱动因素。在这项回顾性研究中，我们分析了弥漫性大B细胞淋巴瘤患者中脂肪酸合酶（从头脂肪酸合成中的关键酶）、Spot 14（甲状腺激素反应性Spot 14，一种促进脂肪酸合成相关基因表达的核蛋白）和CD36（外源性脂肪酸摄取的细胞表面通道）的表达及其临床意义。我们观察到，脂肪酸合酶的过表达与弥漫性大B细胞淋巴瘤患者的总生存期（P = 0.001）和无进展生存期（P = 0.004）呈负相关。多变量分析表明，脂肪酸合酶过表达是侵袭性临床病程的独立预后标志物。我们首次报道CD36是接受利妥昔单抗治疗患者的独立保护因素。因此，脂肪酸合酶和CD36表达可能作为预后标志物，用于预测弥漫性大B细胞淋巴瘤患者的治疗反应和生存情况。脂肪酸合酶也可能是淋巴系统恶性肿瘤的潜在治疗靶点。
