Tian Yunjie, Dong Ruoyu, Guan Yingxia, Wang Ying, Zhao Wei, Zhang Jun, Kang Shan
Department of Gynecology, The Fourth Hospital of Hebei Medical University, No.12 Jiankang Road, Shijiazhuang, 050000, Hebei, China.
Department of Vascular Surgery, Hebei General Hospital, No.348 Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei, China.
J Transl Med. 2025 Jan 28;23(1):129. doi: 10.1186/s12967-025-06135-9.
Immune cells within tumor tissues play important roles in remodeling the tumor microenvironment, thus affecting tumor progression and the therapeutic response. The current study was designed to identify key markers of plasma cells and explore their role in high-grade serous ovarian cancer (HGSOC).
We utilized single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify key immune cell types within HGSOC tissues and to extract related markers via the Seurat package. The effects of immune cell markers on prognosis were analyzed via univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and gene set variation analysis (GSVA) of bulk sequencing data from The Cancer Genome Atlas (TCGA)-HGSOC cohort. Finally, the effects of key markers on HGSOC cells were evaluated via Cell Counting Kit-8 (CCK-8), Transwell, colony formation, wound healing, immunofluorescence and in vivo tumor growth assays.
At the single-cell level, we detected a significant increase in the proportion of plasma cells in HGSOC samples compared to that in normal ovarian samples. Within HGSOC tissues, these plasma cells were found to interact with CD8 + T cells, fibroblasts and endothelial cells. In addition, patients in the high-plasma cell-related score group had better survival rates and higher epithelial‒mesenchymal transition (EMT), apoptosis and immune scores. Moreover, univariate Cox and LASSO regression analyses revealed that ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is a prognostic marker in HGSOC. Further functional studies revealed that overexpression of UBE2J1 promoted cell proliferation, invasion, migration and colony formation, whereas UBE2J1 knockdown attenuated the abovementioned cellular behaviors. Additionally, UBE2J1 overexpression promoted EMT, as evidenced by alterations in the protein expression levels of N-cadherin, snail family transcriptional repressor 2 (Slug), Twist family BHLH transcription factor 1 (Twist 1) and E-cadherin. Moreover, we found that UBE2J1 silencing was able to inhibit the tumor growth in vivo.
Overall, this study elucidated the role of plasma cells and revealed UBE2J1 as a novel oncogene in HGSOC, uncovering new mechanisms related to HGSOC tumorigenesis and promising therapeutic targets for HGSOC patients.
肿瘤组织内的免疫细胞在重塑肿瘤微环境中发挥重要作用，从而影响肿瘤进展和治疗反应。本研究旨在鉴定浆细胞的关键标志物，并探讨其在高级别浆液性卵巢癌（HGSOC）中的作用。
我们利用来自基因表达综合数据库（GEO）的单细胞测序数据，以鉴定HGSOC组织内的关键免疫细胞类型，并通过Seurat软件包提取相关标志物。通过单变量Cox回归、最小绝对收缩和选择算子（LASSO）以及对来自癌症基因组图谱（TCGA）-HGSOC队列的批量测序数据进行基因集变异分析（GSVA），分析免疫细胞标志物对预后的影响。最后，通过细胞计数试剂盒-8（CCK-8）、Transwell实验、集落形成实验、伤口愈合实验、免疫荧光实验以及体内肿瘤生长实验，评估关键标志物对HGSOC细胞的影响。
在单细胞水平上，我们检测到与正常卵巢样本相比，HGSOC样本中浆细胞的比例显著增加。在HGSOC组织内，发现这些浆细胞与CD8 + T细胞、成纤维细胞和内皮细胞相互作用。此外，高浆细胞相关评分组的患者生存率更高，上皮-间质转化（EMT）、凋亡和免疫评分也更高。此外，单变量Cox和LASSO回归分析显示，泛素结合酶E2 J1（UBE2J1）是HGSOC的一个预后标志物。进一步的功能研究表明，UBE2J1的过表达促进细胞增殖、侵袭、迁移和集落形成，而UBE2J1的敲低则减弱上述细胞行为。此外，UBE2J1的过表达促进EMT，这通过N-钙黏蛋白、蜗牛家族转录抑制因子2（Slug）、Twist家族BHLH转录因子1（Twist 1）和E-钙黏蛋白的蛋白表达水平变化得以证明。此外，我们发现UBE2J1的沉默能够抑制体内肿瘤生长。
总体而言，本研究阐明了浆细胞的作用，并揭示UBE2J1是HGSOC中的一个新致癌基因，揭示了与HGSOC肿瘤发生相关的新机制，并为HGSOC患者提供了有前景的治疗靶点。
