Transcriptome Profiling Reveals B-Lineage Cells Contribute to the Poor Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma

Yang, Fafen; Zhao, Jingjie; Luo, Xiuzhuang; Li, Tong; Wang, Zechen; Wei, Qiuju; Lu, Heming; Meng, Yiliang; Cai, Kai; Lu, Liuying; Lu, Yushi; Chen, Lifen; Sooranna, Suren Rao; Luo, Linxue; Song, Jian; Meng, Lingzhang

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.