Single-cell RNA sequencing revealed tumor heterogeneity in multiple pathologic types of renal cell carcinoma

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 tumour heterogeneity is probably reflected at the mRNA level, the study of mRNA in RCC may reveal tumour heterogeneity, especially single-cell RNA sequencing (scRNA-seq). However, the single-cell transcriptome of RCC has been poorly reported and type 2 papillary RCC (pRCC) and chromophobe RCC (chRCC) have not been reported yet. 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 four different normal kidneys, providing 23,951 single-cell transcriptome information. Tumour heterogeneity was well revealed by the comparison between different pathological types of RCC and normal kidneys at the scRNA level. Some new tumour-specific markers for different pathologic types of RCC, such as <i>SPOCK1</i>, <i>PTGIS</i>, <i>NDUFA4L2</i>, <i>REG1A</i>, <i>RHCG</i> and <i>SPAG4 </i>were identified and validated. The subtypes of different pathological types of RCC were differentiated and tumour cell subtypes that affected the prognosis in chRCC were discovered. 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 <i>POSTN</i> and <i>COL3A1</i>. The activation of drug target pathways and sensitivity to drug responses was predicted in different pathological types of RCC. Taken together, these findings considerably enriched the single-cell transcriptomic information for RCC, thereby providing new insights into the diagnosis and treatment of RCC.