Division of Hematology and Medical Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan.
Department of Pathology, MacKay Memorial Hospital, Tamsui Branch, New Taipei City 25160, Taiwan.
Int J Mol Sci. 2020 Sep 18;21(18):6851. doi: 10.3390/ijms21186851.
Reprogramming of cellular energy metabolism, such as lipid metabolism, is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). However, whether protein expression related to fatty acid oxidation (FAO) affects survival in SCCHN remains unclear. We aimed to investigate FAO-related enzyme expression and determine its correlation with clinicopathological variables in SCCHN patients. Immunohistochemical analysis (IHC) of FAO-related protein expression, including carnitine palmitoyltransferase 1 (CPT1), the acyl-CoA dehydrogenase family, and fatty acid synthase (FAS), was performed using tissue microarrays from 102 resected SCCHN tumors. Expressions were categorized according to IHC scores, and the statistical association with clinicopathological factors was determined. Moderate-to-high expression of long-chain acyl-CoA dehydrogenase (LCAD) had a protective role against cancer-related death (adjusted hazard ratio (HR), 0.2; 95% confidence interval (CI), 0.05-0.87) after covariate adjustment. Age and clinical stage remained independent predictors of survival (adjusted HR, 1.75; 95% CI, 1.22-2.49 for age; adjusted HR, 14.33; 95% CI, 1.89-108.60 for stage III/IV disease). Overexpression of medium-chain acyl-CoA dehydrogenase and FAS correlated with advanced tumor stage (T3/T4); however, none of these factors were independent predictors of survival. Several FAO-related enzymes were upregulated and LCAD overexpression had a protective effect on overall survival in advanced SCCHN patients. FAO-related-enzyme expression might have a prognostic impact on survival outcomes in SCCHN.
细胞能量代谢的重编程,如脂质代谢,是头颈部鳞状细胞癌(SCCHN)的一个标志。然而,脂肪酸氧化(FAO)相关蛋白表达是否影响 SCCHN 患者的生存尚不清楚。我们旨在研究 FAO 相关酶的表达,并确定其与 SCCHN 患者的临床病理变量的相关性。使用 102 例切除的 SCCHN 肿瘤的组织微阵列进行 FAO 相关蛋白表达(包括肉碱棕榈酰转移酶 1(CPT1)、酰基辅酶 A 脱氢酶家族和脂肪酸合酶(FAS))的免疫组织化学分析(IHC)。根据 IHC 评分对表达进行分类,并确定与临床病理因素的统计学关联。长链酰基辅酶 A 脱氢酶(LCAD)的中高度表达对癌症相关死亡具有保护作用(调整后的危险比(HR),0.2;95%置信区间(CI),0.05-0.87),在调整协变量后。年龄和临床分期仍然是生存的独立预测因素(调整后的 HR,1.75;95%CI,1.22-2.49 用于年龄;调整后的 HR,14.33;95%CI,1.89-108.60 用于 III/IV 期疾病)。中链酰基辅酶 A 脱氢酶和 FAS 的过表达与肿瘤晚期(T3/T4)相关;然而,这些因素都不是生存的独立预测因素。几种 FAO 相关酶表达上调,LCAD 过表达对晚期 SCCHN 患者的总生存有保护作用。FAO 相关酶表达可能对 SCCHN 的生存结果有预后影响。