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卵巢癌中基于多基因的免疫预后特征的开发。

Development of a multi-gene-based immune prognostic signature in ovarian Cancer.

机构信息

Department of Gynecology and Obstetrics, Sun Yat-Sen University, First Affiliated Hospital, 58 zhongshan 2nd road, Yuexiu District, Guangzhou, Guangdong, 510070, P.R. China.

出版信息

J Ovarian Res. 2021 Jan 28;14(1):20. doi: 10.1186/s13048-021-00766-4.

Abstract

BACKGROUND

Various components of the immune system play a critical role in the prognosis and treatment response in ovarian cancer (OC). Immunotherapy has been recognized as a hallmark of cancer but the effect is contradictional. Reliable immune gene-based prognostic biomarkers or regulatory factors are necessary to be systematically explored to develop an individualized prediction signature.

METHODS

This study systematically explored the gene expression profiles in patients with ovarian cancer from RNA-seq data set for The Cancer Genome Atlas (TCGA). Differentially expressed immune genes and transcription factors (TFs) were identified using the collected immune genes from ImmPort dataset and TFs from Cistoma database. Survival associated immune genes and TFs were identified in terms of overall survival. The prognostic signature was developed based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, we performed network analysis to uncover the potential regulators of immune-related genes with the help of computational biology.

RESULTS

The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected the immune cells landscape and infiltration of some immune cell subtypes.

CONCLUSIONS

We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, and prognosis of OC patients.

摘要

背景

免疫系统的各种成分在卵巢癌(OC)的预后和治疗反应中起着关键作用。免疫疗法已被认为是癌症的标志,但效果却相互矛盾。有必要系统地探索可靠的基于免疫基因的预后生物标志物或调节因子,以开发个性化的预测特征。

方法

本研究系统地从癌症基因组图谱(TCGA)的 RNA-seq 数据集中探索了卵巢癌患者的基因表达谱。使用从 ImmPort 数据集收集的免疫基因和从 Cistoma 数据库收集的转录因子,鉴定差异表达的免疫基因和转录因子。根据总生存率,确定与生存相关的免疫基因和转录因子。基于与生存相关的免疫基因,使用 LASSO(最小绝对收缩和选择算子)Cox 回归分析开发预后特征。此外,我们借助计算生物学进行网络分析,以揭示免疫相关基因的潜在调节剂。

结果

预后特征是 21 个免疫相关基因的加权组合,在生存预测中表现中等,AUC 分别为 0.746、0.735 和 0.749,用于 1、3 和 5 年总生存率。网络分析揭示了转录因子在免疫基因中的调节作用。有趣的是,预后特征反映了免疫细胞景观和某些免疫细胞亚型的浸润。

结论

我们首次构建了一个包含 21 个具有临床意义的免疫基因的特征,该特征在 OC 患者的监测和预后中表现出有前途的预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd70/7844906/f3e82fbca27e/13048_2021_766_Fig1_HTML.jpg

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