Reduced expression of ferroportin1 and ceruloplasmin predicts poor prognosis in adrenocortical carcinoma
Reduced expression of ferroportin1 and ceruloplasmin predicts poor prognosis in adrenocortical carcinoma
复制标题
铁转运蛋白1和铜蓝蛋白表达降低预示肾上腺皮质癌预后不良
DOI：
10.1016/j.jtemb.2019.07.009
复制
发表时间：
2019-12-01
影响因子：
3.5
通讯作者：
Shi, Liyun
中科院分区：
文献类型：
--
作者：
Zhu, Bo;Zhi, Qi;Shi, Liyun
简介：铁代谢在人体细胞中受到严格控制。铁代谢相关基因的失调已被认为是癌症中有希望的预后生物标志物。然而，铁代谢相关基因在肾上腺皮质癌（ACC）中的表达模式和预后作用仍然未知。 目的：本研究的主要目的是利用公开数据集探讨铁代谢相关基因在 ACC 中的表达模式和预后作用。 方法：在本研究中，我们比较了 ACC 肿瘤（n = 77）和正常肾上腺组织（n = 128）中 36 个铁代谢相关基因的表达模式，基于癌症基因组图谱 (TCGA) 和基因型组织表达 (GTEx) 数据。进一步探讨临床变量（包括生存率和病理阶段）与铁唯心论相关基因表达水平之间的关联。所有生物信息学分析均使用GEPIA或Metascape工具进行。结果：12个铁代谢相关基因在ACC肿瘤和正常对照之间存在差异表达。其中，铁转运蛋白1（FPN1）和铜蓝蛋白（CP）表达水平降低与ACC患者的不良生存率显着相关。特别是，FPN1的表达水平与ACC的病理分期呈负相关。一项泛癌症分析将 FPN1 和 CP 表达的减少描述为 33 种癌症中 ACC 特异性的特征。功能富集分析表明，FPN1 和 CP 可能与多种免疫过程有关。结论：本研究中，FPN1 和 CP 表达减少被认为是 ACC 预后不良的潜在标志。 FPN1 或 CP 在 ACC 中的预后价值的机制值得进一步的实验研究。
Introduction: Iron metabolism is tightly controlled in human cells. Dysregulation of iron metabolism-related genes has been characterized as a promising prognostic biomarker in cancers. However, the expression patterns and prognostic roles of iron metabolism-related genes remain unknown in adrenocortical carcinoma (ACC).Objectives: The primary objective of this study was to explore the expression patterns and prognostic roles of iron metabolism-related genes in ACC using publicly available datasets.Methods: In the present study, we compared the expression patterns of 36 iron metabolism-related genes between ACC tumors (n = 77) and normal adrenal tissues (n = 128) based on The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data. The associations between clinical variables (including survival rate and pathological stage) and expression levels of iron mentalism-related genes were further explored. All the bioinformatics analyses were performed using the GEPIA or the Metascape tool.Results: Twelve iron metabolism-related genes were differentially expressed between ACC tumors and normal controls. Among them, reduced expression levels of ferroportin1 (FPN1) and ceruloplasmin (CP) were significantly correlated with poor survival of ACC patients. Specially, the expression levels of FPN1 were negatively correlated with the pathological stages of ACC. A pan-cancer analysis characterized the reduced expression of FPN1 and CP as an ACC-specific signature among 33 types of cancers. Functional enrichment analysis suggested that both FPN1 and CP might be implicated in several immune processes.Conclusion: Reduced expression of FPN1 and CP was identified as a potential signature for poor prognosis of ACC in this study. Mechanisms underlying the prognostic value of FPN1 or CP in ACC deserve further experimental investigation.