Department of Thyroid Surgery.
Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network.
Medicine (Baltimore). 2021 Apr 23;100(16):e25414. doi: 10.1097/MD.0000000000025414.
Single-cell RNA-seq has become a powerful tool to understand tumor cell heterogenicity. This study tried to screen prognosis-related genes in basal-like breast tumors and evaluate their correlations with cellular states at the single-cell level.Bulk RNA-seq data of basal-like tumor cases from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and single-cell RNA-seq from GSE75688 were retrospectively reviewed. Kaplan-Meier survival curves, univariate and multivariate analysis based on Cox regression model were conducted for survival analysis. Gene set enrichment analysis (GSEA) and single-cell cellular functional state analysis were performed.Twenty thousand five hundred thirty genes with bulk RNA-seq data in TCGA were subjected to screening. Preliminary screening identified 10 candidate progression-related genes, including CDH19, AQP5, SDR16C5, NCAN, TTYH1, XAGE2, RIMS2, GZMB, LY6D, and FAM3B. By checking their profiles using single-cell RNA-seq data, only CDH19, SDR16C5, TTYH1, and RIMS2 had expression in primary triple-negative breast cancer (TNBC) cells. Prognostic analysis only confirmed that RIMS2 expression was an independent prognostic indicator of favorable progression free survival (PFS) (HR: 0.78, 95%: 0.64-0.95, P = .015). GSEA analysis showed that low RIMS2 group expression had genes significantly enriched in DNA Repair, and MYC Targets V2. Among the 89 basal-like cells, RIMS2 expression was negatively correlated with DNA repair and epithelial-to-mesenchymal transition (EMT).RIMS2 expression was negatively associated with DNA repair capability of basal-like breast tumor cells and might serve as an independent indicator of favorable PFS.
单细胞 RNA 测序已成为了解肿瘤细胞异质性的有力工具。本研究试图筛选基底样乳腺癌中的预后相关基因，并评估其与单细胞水平细胞状态的相关性。回顾性分析了来自癌症基因组图谱-乳腺癌（TCGA-BRCA）的基底样肿瘤病例的批量 RNA 测序数据和 GSE75688 的单细胞 RNA 测序数据。进行 Kaplan-Meier 生存曲线、基于 Cox 回归模型的单变量和多变量分析以进行生存分析。进行基因集富集分析（GSEA）和单细胞细胞功能状态分析。在 TCGA 的批量 RNA 测序数据中，有 25300 个基因被筛选。初步筛选出 10 个候选进展相关基因，包括 CDH19、AQP5、SDR16C5、NCAN、TTYH1、XAGE2、RIMS2、GZMB、LY6D 和 FAM3B。通过使用单细胞 RNA 测序数据检查它们的图谱，只有 CDH19、SDR16C5、TTYH1 和 RIMS2 在原发性三阴性乳腺癌（TNBC）细胞中有表达。预后分析仅证实 RIMS2 表达是无进展生存期（PFS）的独立预后指标（HR：0.78，95%：0.64-0.95，P=0.015）。GSEA 分析表明，低 RIMS2 组表达的基因在 DNA 修复和 MYC Targets V2 中显著富集。在 89 个基底样细胞中，RIMS2 表达与 DNA 修复和上皮-间充质转化（EMT）呈负相关。RIMS2 表达与基底样乳腺癌细胞的 DNA 修复能力呈负相关，可能作为 PFS 良好的独立指标。
