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整合加权基因共表达网络分析揭示与高级别浆液性卵巢癌预后相关的生物标志物。

Integrated weighted gene co-expression network analysis reveals biomarkers associated with prognosis of high-grade serous ovarian cancer.

机构信息

Maternal & Child Health Research Institute, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China.

Institutes for Shanghai Pudong Decoding Life, Shanghai, China.

出版信息

J Clin Lab Anal. 2022 Feb;36(2):e24165. doi: 10.1002/jcla.24165. Epub 2022 Jan 8.

Abstract

BACKGROUND

Ovarian cancer is the gynecologic tumor with the highest fatality rate, and high-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer. One important reason for the poor prognosis of HGSOC is the lack of effective diagnostic and prognostic biomarkers. New biomarkers are necessary for the improvement of treatment strategies and to ensure appropriate healthcare decisions.

METHODS

To construct the co-expression network of HGSOC samples, we applied weighted gene co-expression network analysis (WGCNA) to assess the proteomic data obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and module-trait relationship was then analyzed and plotted in a heatmap to choose key module associated with HGSOC. Subsequently, hub genes with high connectivity in key module were identified by Cytoscape software. Furthermore, the biomarkers were selected through survival analysis, followed by evaluation using the relative operating characteristic (ROC) analysis.

RESULTS

A total of 9 modules were identified by WGCNA, and module-trait analysis revealed that the brown module was significantly associated with HGSOC (cor = 0.7). Ten hub genes with the highest connectivity were selected by protein-protein interaction analysis. After survival and ROC analysis, ALB, APOB and SERPINA1 were suggested to be the biomarkers, and their protein levels were positively correlated with HGSOC prognosis.

CONCLUSION

We conducted the first gene co-expression analysis using proteomic data from HGSOC samples, and found that ALB, APOB and SERPINA1 had prognostic value, which might be applied for the treatment of HGSOC in the future.

摘要

背景

卵巢癌是致死率最高的妇科肿瘤,而高级别浆液性卵巢癌(HGSOC)是最常见和恶性的卵巢癌类型。HGSOC 预后差的一个重要原因是缺乏有效的诊断和预后生物标志物。新的生物标志物对于改进治疗策略和确保适当的医疗保健决策是必要的。

方法

为了构建 HGSOC 样本的共表达网络,我们应用加权基因共表达网络分析(WGCNA)来评估来自临床蛋白质组肿瘤分析联盟(CPTAC)的蛋白质组数据,然后分析模块-特征关系,并绘制热图以选择与 HGSOC 相关的关键模块。随后,通过 Cytoscape 软件识别关键模块中具有高连接性的枢纽基因。此外,通过生存分析选择生物标志物,然后使用相对工作特征(ROC)分析进行评估。

结果

WGCNA 共鉴定出 9 个模块,模块-特征分析表明棕色模块与 HGSOC 显著相关(cor=0.7)。通过蛋白质-蛋白质相互作用分析选择了 10 个具有最高连接性的枢纽基因。经过生存和 ROC 分析,ALB、APOB 和 SERPINA1 被认为是生物标志物,其蛋白水平与 HGSOC 预后呈正相关。

结论

我们首次使用 HGSOC 样本的蛋白质组数据进行基因共表达分析,发现 ALB、APOB 和 SERPINA1 具有预后价值,可能应用于未来 HGSOC 的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5206/8841170/5eb2d3986165/JCLA-36-e24165-g007.jpg

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