Moon Sun Joon, Kim Jung Hee, Kong Sung Hye, Shin Chan Soo
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2020 Mar;35(1):132-141. doi: 10.3803/EnM.2020.35.1.132.
Adrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.
We used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.
In 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82-0.86; cfNRI, all values <0.05).
In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.
肾上腺皮质癌（ACC）是一种预后各异的罕见癌症。此前已报道了几种ACC的预后因素，但尚未进行蛋白质组学分析。本研究旨在采用蛋白质组学方法研究ACC的预后生物标志物。
我们使用了来自癌症蛋白质组图谱的反相蛋白质阵列数据，并鉴定了转移性ACC中差异表达的蛋白质。采用经年龄和分期调整的多变量Cox回归分析进行生存分析，并利用C指数和无类别净重新分类改善（cfNRI）来评估附加预后价值。
在46例ACC患者中，细胞周期蛋白B1、转铁蛋白受体（TfR1）和纤连蛋白在远处转移患者中显著过表达。在多变量模型中，细胞周期蛋白B1和TfR1的高表达与死亡率显著相关（风险比[HR]，6.13；95%置信区间[CI]，1.02至36.7；以及HR，6.59；95%CI，1.14至38.2），而纤连蛋白高表达则不然（HR，3.92；95%CI，0.75至20.4）。细胞周期蛋白B1高表达/TfR1高表达、细胞周期蛋白B1高表达/纤连蛋白高表达以及TfR1高表达/纤连蛋白高表达的组合与死亡率密切相关（分别为[HR，13.72；95%CI，1.89至99.66]、[HR，9.22；95%CI，1.34至63.55]和[HR,18.59；95%CI，2.54至135.88]）。在重新分类分析中，细胞周期蛋白B1、TfR1、纤连蛋白及其组合改善了预后性能（C指数，从0.78提高到0.82 - 0.86；cfNRI，所有值<0.05）。
在ACC患者中，细胞周期蛋白B1、TfR1和纤连蛋白及其组合的过表达与预后不良相关。
