Transcriptome Profiling Reveals B-Lineage Cells Contribute to the Poor Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma.
Transcriptome Profiling Reveals B-Lineage Cells Contribute to the Poor Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma.
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DOI：
10.3389/fonc.2021.731896
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发表时间：
2021
影响因子：
4.7
通讯作者：
Meng L
中科院分区：
文献类型：
--
作者：
Yang F;Zhao J;Luo X;Li T;Wang Z;Wei Q;Lu H;Meng Y;Cai K;Lu L;Lu Y;Chen L;Sooranna SR;Luo L;Song J;Meng L
尽管免疫治疗可以显着改善透明细胞肾细胞癌（ccRCC）的治疗效果，但仍有很大比例的ccRCC患者进展至转移。针对 ccRCC 微环境中的促转移免疫细胞可以为该问题提供解决方案。在本研究中，通过使用 scRNA-seq 和流式细胞术鉴定了 ccRCC 活检中的 B 细胞。研究结果表明存在促转移 B 细胞类型，根据其大规模遗传图谱，可将其进一步分为 3 个亚群：MARCH3、B2M 和 DTWD1，而不是传统的未成熟/成熟亚群。尽管所有 3 个亚群似乎都有助于远处转移，但 B 细胞 (B2M) 被认为是最重要的。此外，STX16、CLASRP、ATIC、ACIN1 和 SEMA4B 是在 3 个亚群中普遍上调的基因，这与 ccRCC 的不良预后相关。此外，ccRCC 中浆细胞的异质性也被发现有助于该疾病的转移。该研究提供了针对癌症远处转移的潜在新治疗靶点，有助于提高ccRCC患者的治疗效率。
Although immune therapy can improve the treatment of clear cell renal cell carcinoma (ccRCC) significantly, there are still a large proportion of ccRCC patients who progress to metastasis. Targeting the pro-metastatic immune cell in the ccRCC microenvironment could provide a solution to this problem. In this study, B cells in ccRCC biopsies were identified by using scRNA-seq and flow cytometry. The findings indicated the presence of a pro-metastatic B cell type which could be further classified into 3 subpopulations, MARCH3, B2M and DTWD1, based on their large-scaled genetic profiles, rather than traditional Immature/Mature ones. Although all of the 3 subpopulations appeared to contribute to distant metastasis, B cell (B2M) was deemed to be the most essential. Moreover, STX16, CLASRP, ATIC, ACIN1 and SEMA4B, were genes found to be commonly up-regulated in the 3 subpopulations and this was correlated to a poor prognosis of ccRCC. Furthermore, the heterogeneity of plasma cells in ccRCC was also found to contribute to metastasis of the disease. This study offers potential novel therapeutic targets against distant metastasis of cancers, and can help to improve the therapeutic efficiency of ccRCC patients.
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