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蛋白质表达谱分析鉴定出一种卵巢癌预后模型。

Protein expression profiling identifies a prognostic model for ovarian cancer.

机构信息

Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Obstetrics and Gynecology, National Key Clinical Specialty of Gynecology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.

出版信息

BMC Womens Health. 2022 Jul 15;22(1):292. doi: 10.1186/s12905-022-01876-x.

Abstract

BACKGROUND

Owing to the high morbidity and mortality, ovarian cancer has seriously endangered female health. Development of reliable models can facilitate prognosis monitoring and help relieve the distress.

METHODS

Using the data archived in the TCPA and TCGA databases, proteins having significant survival effects on ovarian cancer patients were screened by univariate Cox regression analysis. Patients with complete information concerning protein expression, survival, and clinical variables were included. A risk model was then constructed by performing multiple Cox regression analysis. After validation, the predictive power of the risk model was assessed. The prognostic effect and the biological function of the model were evaluated using co-expression analysis and enrichment analysis.

RESULTS

394 patients were included in model construction and validation. Using univariate Cox regression analysis, we identified a total of 20 proteins associated with overall survival of ovarian cancer patients (p < 0.01). Based on multiple Cox regression analysis, six proteins (GSK3α/β, HSP70, MEK1, MTOR, BAD, and NDRG1) were used for model construction. Patients in the high-risk group had unfavorable overall survival (p < 0.001) and poor disease-specific survival (p = 0.001). All these six proteins also had survival prognostic effects. Multiple Cox regression analysis demonstrated the risk model as an independent prognostic factor (p < 0.001). In receiver operating characteristic curve analysis, the risk model displayed higher predictive power than age, tumor grade, and tumor stage, with an area under the curve value of 0.789. Analysis of co-expressed proteins and differentially expressed genes based on the risk model further revealed its prognostic implication.

CONCLUSIONS

The risk model composed of GSK3α/β, HSP70, MEK1, MTOR, BAD, and NDRG1 could predict survival prognosis of ovarian cancer patients efficiently and help disease management.

摘要

背景

由于卵巢癌的高发病率和死亡率,它严重威胁着女性健康。开发可靠的模型可以促进预后监测,并有助于缓解患者的痛苦。

方法

利用 TCPA 和 TCGA 数据库中的数据,通过单因素 Cox 回归分析筛选对卵巢癌患者具有显著生存影响的蛋白质。纳入具有完整蛋白质表达、生存和临床变量信息的患者。然后通过多因素 Cox 回归分析构建风险模型。验证后,评估风险模型的预测能力。通过共表达分析和富集分析评估模型的预后效果和生物学功能。

结果

在模型构建和验证中纳入了 394 名患者。通过单因素 Cox 回归分析,我们总共鉴定出 20 种与卵巢癌患者总生存相关的蛋白质(p<0.01)。基于多因素 Cox 回归分析,使用 6 种蛋白质(GSK3α/β、HSP70、MEK1、MTOR、BAD 和 NDRG1)构建模型。高风险组的患者总体生存不良(p<0.001),疾病特异性生存不良(p=0.001)。所有这 6 种蛋白质也具有生存预后作用。多因素 Cox 回归分析表明,风险模型是独立的预后因素(p<0.001)。在接受者操作特征曲线分析中,风险模型比年龄、肿瘤分级和肿瘤分期具有更高的预测能力,曲线下面积值为 0.789。基于风险模型的共表达蛋白和差异表达基因分析进一步揭示了其预后意义。

结论

由 GSK3α/β、HSP70、MEK1、MTOR、BAD 和 NDRG1 组成的风险模型可以有效地预测卵巢癌患者的生存预后,有助于疾病管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cb4/9284690/f6acd80286ba/12905_2022_1876_Fig1_HTML.jpg

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