Identification of a Novel Stem Cell Subtype for Clear Cell Renal Cell Carcinoma Based on Stem Cell Gene Profiling

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and is characterized by high rates of metastasis. Cancer stem cell is a vital cause of renal cancer metastasis and recurrence. However, little is known regarding the change and the roles of stem cells during the development of renal cancer. To clarify this problem, we developed a novel stem cell clustering strategy. Based on The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) genomic datasets, we used 19 stem cell gene sets to classify each dataset. A machine learning method was used to perform the classification. We classified ccRCC into three subtypes—stem cell activated (SC-A), stem cell dormant (SC-D), and stem cell excluded (SC-E)—based on the expressions of stem cell-related genes. Compared with the other subtypes, C2(SC-A) had the highest degree of cancer stem cell concentration, the highest level of immune cell infiltration, a distinct mutation landscape, and the worst prognosis. Moreover, drug sensitivity analysis revealed that subgroup C2(SC-A) had the highest sensitivity to immunotherapy CTLA-4 blockade and the vascular endothelial growth factor receptor (VEGFR) inhibitor sunitinib. The identification of ccRCC subtypes based on cancer stem cell gene sets demonstrated the heterogeneity of ccRCC and provided a new strategy for its treatment.