Xie Bingqing, Olalekan Susan, Back Rebecca, Ashitey Naa Asheley, Eckart Heather, Basu Anindita
Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, United States.
Front Cell Dev Biol. 2024 Jan 24;11:1297219. doi: 10.3389/fcell.2023.1297219. eCollection 2023.
Ovarian cancer is a highly heterogeneous disease consisting of at least five different histological subtypes with varying clinical features, cells of origin, molecular composition, risk factors, and treatments. While most single-cell studies have focused on High grade serous ovarian cancer, a comprehensive landscape of the constituent cell types and their interactions within the tumor microenvironment are yet to be established in the different ovarian cancer histotypes. Further characterization of tumor progression, metastasis, and various histotypes are also needed to connect molecular signatures to pathological grading for personalized diagnosis and tailored treatment. In this study, we leveraged high-resolution single-cell RNA sequencing technology to elucidate the cellular compositions on 21 solid tumor samples collected from 12 patients with six ovarian cancer histotypes and both primary (ovaries) and metastatic (omentum, rectum) sites. The diverse collection allowed us to deconstruct the histotypes and tumor site-specific expression patterns of cells in the tumor, and identify key marker genes and ligand-receptor pairs that are active in the ovarian tumor microenvironment. Our findings can be used in improving precision disease stratification and optimizing treatment options.
卵巢癌是一种高度异质性疾病,由至少五种不同的组织学亚型组成,具有不同的临床特征、起源细胞、分子组成、风险因素和治疗方法。虽然大多数单细胞研究都集中在高级别浆液性卵巢癌上,但在不同的卵巢癌组织学类型中,肿瘤微环境中组成细胞类型及其相互作用的全面图景尚未建立。还需要进一步表征肿瘤进展、转移和各种组织学类型,以便将分子特征与病理分级联系起来,实现个性化诊断和定制治疗。在本研究中,我们利用高分辨率单细胞RNA测序技术,阐明了从12例患有六种卵巢癌组织学类型的患者的原发(卵巢)和转移(大网膜、直肠)部位收集的21个实体瘤样本中的细胞组成。这种多样化的样本收集使我们能够解构肿瘤中细胞的组织学类型和肿瘤部位特异性表达模式,并识别在卵巢肿瘤微环境中活跃的关键标记基因和配体-受体对。我们的研究结果可用于改善精准疾病分层和优化治疗方案。