Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories
Xiu-wu Pan,
Wen-jin Chen,
Da Xu,
Wen-bin Guan,
Lin Li,
Jia-xin Chen,
Wei-jie Chen,
Ke-qin Dong,
Jian-qing Ye,
Si-shun Gan,
Wang Zhou,
Xin-gang Cui
Affiliations
Xiu-wu Pan
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China
Wen-jin Chen
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China; Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 700 Moyu North Road, Shanghai 201805, China
Da Xu
Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 700 Moyu North Road, Shanghai 201805, China
Wen-bin Guan
Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China
Lin Li
Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 700 Moyu North Road, Shanghai 201805, China
Jia-xin Chen
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China
Wei-jie Chen
Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 700 Moyu North Road, Shanghai 201805, China
Ke-qin Dong
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China
Jian-qing Ye
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China
Si-shun Gan
Department of Urology, Third Affiliated Hospital of the Second Military Medical University, 700 Moyu North Road, Shanghai 201805, China; Corresponding author
Wang Zhou
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China; Corresponding author
Xin-gang Cui
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China; Corresponding author
Summary: Previous bulk RNA sequencing or whole genome sequencing on clear cell renal cell carcinoma (ccRCC) subtyping mainly focused on ccRCC cell origin or the complex tumor microenvironment (TME). Based on the single-cell RNA sequencing (scRNA-seq) data of 11 primary ccRCC specimens, cancer stem-cell-like subsets could be differentiated into five trajectories, whereby we further classified ccRCC cells into three groups with diverse molecular features. These three ccRCC subgroups showed significantly different outcomes and potential targets to tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). Tumor cells in three differentiation directions exhibited distinct interactions with other subsets in the ccRCC niches. The subtyping model was examined through immunohistochemistry staining in our ccRCC cohort and validated the same classification effect as the public patients. All these findings help gain a deeper understanding about the pathogenesis of ccRCC and provide useful clues for optimizing therapeutic schemes based on the molecular subtype analysis.
