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利用单细胞 RNA 测序技术鉴定葡萄膜黑色素瘤的异质性和预后关键基因。

Identification of heterogeneity and prognostic key genes associated with uveal melanoma using single-cell RNA-sequencing technology.

机构信息

Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin.

Department of Ophthalmology, Yuncheng Central Hospital, Shanxi Medical University, Yuncheng, Shanxi Province.

出版信息

Melanoma Res. 2022 Feb 1;32(1):18-26. doi: 10.1097/CMR.0000000000000783.

Abstract

Uveal melanoma (UM) is the most common intraocular malignancy in adults. The prognosis is poor once metastasis has developed. The treatment of metastatic UM remains challenging nowadays due to lacking a deep understanding of the biological characteristics of this disease. Here, we revealed the cell subpopulations with distinct functional status and the existence of cells with high invasive potential within heterogeneous primary and metastatic UM. The single-cell sequencing data were retrieved from GSE139829 and GSE138433, through which we identified a new cell cluster related to metastatic UM as a unique type of immune cell. The cell-cell communication was conducted by 'Cellchat' to understand the cell crosstalk between these immune cells and their surrounding cells. The crucial signals contributing most to outgoing or incoming signaling of this cell group were identified to reveal the crucial pathway genes. Furthermore, we judged the prognostic value of these candidates on the basis of the data downloaded from The Cancer Genome Atlas. The results demonstrated that the increased IL10, SELPLG, EPHB and ITGB2 signaling pathways could be promising predicting factors for the patient prognosis in UM. Conclusively, we discover the potential key signals of UM for occurrence and metastasis, and also provide a theoretical basis for judging whether there is a high risk of metastasis or recurrence.

摘要

葡萄膜黑色素瘤(UM)是成年人中最常见的眼内恶性肿瘤。一旦发生转移,预后很差。由于对这种疾病的生物学特性缺乏深入了解,目前转移性 UM 的治疗仍然具有挑战性。在这里,我们揭示了具有不同功能状态的细胞亚群以及在异质性原发性和转移性 UM 中存在具有高侵袭潜力的细胞。单细胞测序数据从 GSE139829 和 GSE138433 中检索,通过这些数据,我们确定了一个与转移性 UM 相关的新细胞簇,它是一种独特类型的免疫细胞。通过“Cellchat”进行细胞间通讯,以了解这些免疫细胞与其周围细胞之间的细胞串扰。确定对该细胞群的传出或传入信号贡献最大的关键信号,以揭示关键途径基因。此外,我们根据从癌症基因组图谱下载的数据来判断这些候选物的预后价值。结果表明,IL10、SELPLG、EPHB 和 ITGB2 信号通路的增加可能是 UM 患者预后的有前途的预测因素。总之,我们发现了 UM 发生和转移的潜在关键信号,并为判断是否存在高转移或复发风险提供了理论依据。

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