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Computational modeling of malignant ascites reveals CCL5–SDC4 interaction in the immune microenvironment of ovarian cancer
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2021-03-15 , DOI: 10.1002/mc.23289
Soochi Kim 1 , Youngjin Han 2, 3 , Se Ik Kim 4 , Juwon Lee 2, 3 , HyunA Jo 2, 3 , Wenyu Wang 2, 5 , Untack Cho 2, 5 , Woong-Yang Park 6, 7 , Thomas A Rando 1, 8, 9 , Danny N Dhanasekaran 10, 11 , Yong Sang Song 2, 3, 4, 5
Affiliation  

Fluid accumulation in the abdominal cavity is commonly found in advanced‐stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single‐cell RNA sequencing (scRNA‐seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype‐specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand–receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long‐term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

中文翻译:

恶性腹水的计算模型揭示了卵巢癌免疫微环境中 CCL5-SDC4 的相互作用

腹腔积液常见于晚期卵巢癌患者,这为癌症进展创造了一个专门的肿瘤微环境。使用来自五名卵巢癌患者的腹水细胞的单细胞 RNA 测序 (scRNA-seq),我们确定了七种细胞类型,包括异质巨噬细胞和卵巢癌细胞。我们通过 MacSpectrum 分析解决了巨噬细胞的明显极化状态,并观察到与其功能相关的通路的亚型特异性富集。通过使用 NicheNet 的假定配体-受体对分析预测免疫细胞和癌细胞之间的通信。我们发现 CCL5 是一种趋化配体,富含免疫细胞(T 细胞和 NK 细胞),并可能通过 SDC4 介导腹水中的卵巢癌细胞存活。而且,SDC4 表达与卵巢癌患者较差的总生存期相关。我们的研究强调了 T 细胞和 NK 细胞在卵巢癌长期生存患者中的潜在作用,表明 SDC4 是卵巢癌患者潜在的预后标志物。
更新日期:2021-04-08
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