Wang Xiangru, Chen Hanghang
Department of General Surgery, The Affiliated Hospital Of Henan Medical College, Henan Medical College Hospital Workers, Zhengzhou, China.
Southern Medical University, Guangzhou, China.
Front Genet. 2022 Jul 1;13:928175. doi: 10.3389/fgene.2022.928175. eCollection 2022.
Genomic and antigenic heterogeneity pose challenges in the precise assessment of outcomes of triple-negative breast cancer (TNBC) patients. Thus, this study was designed to investigate the cardinal genes related to cell differentiation and tumor malignant grade to advance the prognosis prediction in TNBC patients through an integrated analysis of single-cell and bulk RNA-sequencing (RNA-seq) data. We collected RNA-seq and microarray data of TNBC from two public datasets. Using single-cell pseudotime analysis, differentially expressed genes (DEGs) among trajectories from 1534 cells of 6 TNBC patients were identified as the potential genes crucial for cell differentiation. Furthermore, the grade- and tumor mutational burden (TMB)-related DEGs were explored via a weighted correlation network analysis using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Subsequently, we utilized the DEGs to construct a prognostic signature, which was validated using another independent dataset. Moreover, as gene set variation analysis indicated the differences in immune-related pathways between different risk groups, we explored the immune differences between the two groups. A signature including 10 genes related to grade and TMB was developed to assess the outcomes of TNBC patients, and its prognostic efficacy was prominent in two cohorts. The low-risk group generally harbored lower immune infiltration compared to the high-risk group. Cell differentiation and grade- and TMB-related DEGs were identified using single-cell and bulk RNA-seq data. A 10-gene signature for prognosis prediction in TNBC patients was constructed, and its performance was excellent. Interestingly, the signature was found to be closely related to tumor immune infiltration, which might provide evidence for the crucial roles of immune cells in malignant initiation and progression in TNBC.
基因组和抗原异质性给三阴性乳腺癌（TNBC）患者预后的精确评估带来了挑战。因此，本研究旨在通过对单细胞和批量RNA测序（RNA-seq）数据的综合分析，研究与细胞分化和肿瘤恶性程度相关的关键基因，以推进TNBC患者的预后预测。我们从两个公共数据集中收集了TNBC的RNA-seq和微阵列数据。通过单细胞拟时间分析，将6例TNBC患者的1534个细胞轨迹中的差异表达基因（DEG）鉴定为对细胞分化至关重要的潜在基因。此外，使用国际乳腺癌分子分类数据集，通过加权相关网络分析探索了与分级和肿瘤突变负荷（TMB）相关的DEG。随后，我们利用这些DEG构建了一个预后特征，并使用另一个独立数据集进行了验证。此外，由于基因集变异分析表明不同风险组之间免疫相关途径存在差异，我们探索了两组之间的免疫差异。开发了一个包含10个与分级和TMB相关基因的特征来评估TNBC患者的预后，其在两个队列中的预后效能显著。与高风险组相比，低风险组的免疫浸润通常较低。利用单细胞和批量RNA-seq数据鉴定了细胞分化以及与分级和TMB相关的DEG。构建了一个用于预测TNBC患者预后的10基因特征，其性能优异。有趣的是，发现该特征与肿瘤免疫浸润密切相关，这可能为免疫细胞在TNBC恶性起始和进展中的关键作用提供证据。
