Single-Cell RNA Sequencing in Multiple Pathologic Types of Renal Cell Carcinoma Revealed Novel Potential Tumor-Specific Markers.

BACKGROUND

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Studying the pathogenesis of RCC is particularly important, because it could provide a direct guide for clinical treatment. Given that tumor heterogeneity is probably reflected at the mRNA level, the study of mRNA in RCC may reveal some potential tumor-specific markers, especially single-cell RNA sequencing (scRNA-seq).

METHODS

We performed an exploratory study on three pathological types of RCC with a small sample size. This study presented clear-cell RCC (ccRCC), type 2 pRCC, and chRCC in a total of 30,263 high-quality single-cell transcriptome information from three pathological types of RCC. In addition, scRNA-seq was performed on normal kidneys. Tumor characteristics were well identified by the comparison between different pathological types of RCC and normal kidneys at the scRNA level.

RESULTS

Some new tumor-specific markers for different pathologic types of RCC, such as and were identified and validated. We also discovered that both highly expressed in tumor cells of ccRCC and type 2 pRCC. The presence of two different types of endothelial cells in ccRCC and type 2 pRCC was also identified and verified. An endothelial cell in ccRCC may be associated with fibroblasts and significantly expressed fibroblast markers, such as and . At last, by applying scRNA-seq results, the activation of drug target pathways and sensitivity to drug responses was predicted in different pathological types of RCC.

CONCLUSIONS

Taken together, these findings considerably enriched the single-cell transcriptomic information for RCC, thereby providing new insights into the diagnosis and treatment of RCC.