Meng Lingnan, Sun Shujuan
Department of Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150007, China.
Discov Oncol. 2024 Sep 9;15(1):417. doi: 10.1007/s12672-024-01290-9.
The heterogeneity of high-grade serous ovarian carcinoma (HGSOC) has hindered the clinical treatment, and our current study aims to characterize the change in tumor microenvironment (TME) with the progression of HGSOC via single cell RNA sequencing (scRNA-seq).
The single-cell landscape in HGSOC was downloaded from the dataset GSE184880, which included 7 HGSOC and 5 normal samples and then applied for the filtering and annotation of cell clusters. The differentially expressed marker genes in these clusters were analyzed via "FindAllMarker" function in Seurat package and the functional enrichment analyses were implemented using clusterProflier package. Finally, the CellChat package was applied for the cell-cell communication analysis. Cellular experimental were determined Real-time Reverse Transcription Polymerase Chain Reaction (RT-qPCR).
45,448 single cells were categorized into 10 cell clusters. The proportion of NK/T cells (49.5%), epithelial cells (15.3%) and myeloid cells (14%) was higher in the HGSOC samples. The heterogeneity and different enriched pathways of epithelial cells have been revealed with the progression of HGSOC from early to late stage, concurrent with the reduced activity of cytotoxic NK/T cells and the decreased capabilities of recruiting immune cells and presenting antigens in macrophages. Besides, the cell-cell communication analysis has revealed a strong communication of CXCL and CCL signal between M1 macrophages and cytotoxic NK/T cells in early stage of HGSOC. Moreover, RT-qPCR indicated that CCL4/5 and CCR1/5 levels were upregulated in tumor cell SK-OV-3.
The investigation using scRNA-seq has depicted the change in cytotoxic NK/T cells, epithelial cells and myeloid cells of the TME of HGSOC, which may provide another insight into the specific mechanisms underlying the progression of HGSOC.
高级别浆液性卵巢癌（HGSOC）的异质性阻碍了临床治疗，我们当前的研究旨在通过单细胞RNA测序（scRNA-seq）来表征HGSOC进展过程中肿瘤微环境（TME）的变化。
从数据集GSE184880下载HGSOC中的单细胞图谱，其中包括7个HGSOC样本和5个正常样本，然后用于细胞簇的过滤和注释。通过Seurat软件包中的“FindAllMarker”函数分析这些簇中差异表达的标记基因，并使用clusterProflier软件包进行功能富集分析。最后，应用CellChat软件包进行细胞间通讯分析。通过实时逆转录聚合酶链反应（RT-qPCR）确定细胞实验结果。
45448个单细胞被分为10个细胞簇。HGSOC样本中NK/T细胞（49.5%）、上皮细胞（15.3%）和髓样细胞（14%）的比例较高。随着HGSOC从早期到晚期的进展，上皮细胞的异质性和不同的富集途径被揭示出来，同时细胞毒性NK/T细胞的活性降低，巨噬细胞招募免疫细胞和呈递抗原的能力下降。此外，细胞间通讯分析显示，在HGSOC早期，M1巨噬细胞与细胞毒性NK/T细胞之间存在强烈的CXCL和CCL信号通讯。此外，RT-qPCR表明肿瘤细胞SK-OV-3中CCL4/5和CCR1/5水平上调。
使用scRNA-seq进行的研究描绘了HGSOC的TME中细胞毒性NK/T细胞、上皮细胞和髓样细胞的变化，这可能为HGSOC进展的具体机制提供另一种见解。
