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基于单细胞和批量RNA测序的乳腺癌上皮细胞相关预后风险模型

Epithelial cell-related prognostic risk model in breast cancer based on single-cell and bulk RNA sequencing.

作者信息

Xia Man-Zhi, Yan Hai-Chao

机构信息

General Surgery, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, 312000, Zhejiang, China.

Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, 310009, Zhejiang, China.

出版信息

Heliyon. 2024 Aug 28;10(17):e37048. doi: 10.1016/j.heliyon.2024.e37048. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e37048
PMID:39286180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11402982/
Abstract

OBJECTIVE

This study aims to construct an epithelial cell-related prognostic risk model for breast cancer (BRCA) and explore its significance.

METHODS

GSE42568, GSE10780, GSE245601, and TCGA-BRCA datasets were sourced from public databases. Epithelial cell-related differentially expressed genes were identified using single-cell data analysis. Venn diagrams determined the intersecting genes between epithelial cell-related and BRCA-related genes. Batch Kaplan-Meier (K-M) survival analysis identified core intersecting genes for BRCA overall survival. Consensus clustering, enrichment, LASSO, and COX regression analyses were performed on the core intersecting genes, and then a prognostic risk model was constructed. The diagnostic and prognostic effectiveness of the risk model was subsequently evaluated and immune infiltration analysis was conducted. Finally, qRT-PCR was used to verify the expression of genes in the risk model.

RESULTS

There were 374 intersecting genes between epithelial cell-related and BRCA-related genes, among which 51 core intersecting genes were associated with BRCA prognosis. Consensus clustering categorized TCGA-BRCA into C1 and C2, with shared regulation of the estrogen signaling pathway. Three genes (DIRC3, SLC6A2, TUBA3D) were independent predictors of BRCA prognosis, forming the basis for a risk model. Except for exhibiting satisfactory diagnostic efficacy, the risk score elevation correlated with poor prognosis, elevated matrix, immune, and ESTIMATE scores, and negative correlation with microsatellite instability. The results confirmed the differential expression levels of DIRC3, SLC6A2, and TUBA3D.

CONCLUSION

The prognostic risk model associated with epithelial cells demonstrates effective diagnostic performance in BRCA, serving as an independent prognostic factor for BRCA patients. Additionally, it exhibits a correlation with immune scores.

摘要

目的

本研究旨在构建一种用于乳腺癌（BRCA）的上皮细胞相关预后风险模型并探讨其意义。

方法

GSE42568、GSE10780、GSE245601和TCGA - BRCA数据集来源于公共数据库。使用单细胞数据分析鉴定上皮细胞相关的差异表达基因。通过维恩图确定上皮细胞相关基因与BRCA相关基因之间的交集基因。批量Kaplan - Meier（K - M）生存分析确定BRCA总生存的核心交集基因。对核心交集基因进行共识聚类、富集、LASSO和COX回归分析，然后构建预后风险模型。随后评估风险模型的诊断和预后有效性并进行免疫浸润分析。最后，使用qRT - PCR验证风险模型中基因的表达。

结果

上皮细胞相关基因与BRCA相关基因之间有374个交集基因，其中51个核心交集基因与BRCA预后相关。共识聚类将TCGA - BRCA分为C1和C2，雌激素信号通路存在共同调控。三个基因（DIRC3、SLC6A2、TUBA3D）是BRCA预后的独立预测因子，构成了风险模型的基础。风险评分升高除了具有令人满意的诊断效能外，还与预后不良、基质、免疫和ESTIMATE评分升高相关，与微卫星不稳定性呈负相关。结果证实了DIRC3、SLC6A2和TUBA3D的差异表达水平。

结论

与上皮细胞相关的预后风险模型在BRCA中表现出有效的诊断性能，是BRCA患者的独立预后因素。此外，它与免疫评分相关。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a60a/11402982/b25a4f54afa3/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a60a/11402982/d1584a806a36/gr9.jpg
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