Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma
Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma
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卵巢浆液性囊腺癌钠/钾-ATP酶α亚基表达与预后的综合分析
DOI：
10.1186/s12935-020-01414-5
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发表时间：
2020-07-14
影响因子：
5.8
通讯作者：
Lou, Ge
中科院分区：
文献类型：
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作者：
Huang, Wei;Zhang, Yongjian;Lou, Ge
卵巢浆液性囊腺癌（OSC）是世界范围内女性最常见和最致命的妇科癌症；然而，用于诊断和预测OSC预后的生物标志物仍然有限。因此，本研究旨在探讨三磷酸腺苷钠/钾（Na+/K+-ATP）酶α-亚基（ATP1As）是否有助于OSC的诊断和预后指标。方法从癌症基因组图谱（TCGA）程序数据库中下载376例OSC患者的基因表达数据（RNA-Seq）。我们分析中使用的其他数据库包括基因表达Omnibus、国际癌症基因组联盟、基因型组织表达、人类蛋白质图谱、癌症基因组学cbiopportal和癌细胞系百科全书。结果OSC组织中ATP1A1和ATP1A3的表达水平高于正常卵巢组织，而ATP1A2和ATP1A4的表达水平低于正常卵巢组织。ATP1A2过表达与较高的妇产科学联合会（FIGO）分期和组织学分级显著相关。在OSC患者中，ATP1A3 mRNA表达升高与较短的总生存期（OS）和疾病特异性生存期（DSS）显著相关，而ATP1A4 mRNA表达升高与较好的OS和DSS相关。多因素分析显示，主要治疗结果、残余肿瘤、ATP1A3和ATP1A4 mRNA表达是OSC患者OS和DSS的独立预后因素。此外，肿瘤组织中ATP1A1染色丰富。在年龄≥60岁、FIGO分期为III期、组织学分级为G3、TP53突变的患者亚组中，ATP1A3高表达与不良OS和DSS显著相关。atp1a的突变频率为3-5%。结论ATP1A基因家族可能是OSC的潜在诊断或预后指标。此外，ATP1As可能是治疗OSC的有效靶点。
BackgroundOvarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na+/K+-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC.MethodsGene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype-Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia.ResultsThe expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3–5%.ConclusionsThese results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.