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.
Highlights
Renal cancer accounts for 3% of all adult malignancies worldwide, and its incidence have been increasing in recent years
We aimed to identify the subclasses of Clear cell renal cell carcinoma (ccRCC) with different cancer stem cell (CSC) properties based on the expressions of stem cell-related genes
Three hundred and ninety-two stem cellrelated genes were enrolled for subsequent non-negative matrix factorization (NMF) analysis
Summary
Renal cancer accounts for 3% of all adult malignancies worldwide, and its incidence have been increasing in recent years. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer, jeopardizing 70%–80% of renal cell carcinoma (RCC) patients. Over 30% of ccRCC patients have distant metastasis at the time of diagnosis, and one-third of patients with localized ccRCC will develop metastasis after nephrectomy [1,2,3]. The 5-year survival rate of localized ccRCC. Stem Cell Subtype of ccRCC is about 65%; it drops to 10%–20% after cancer metastasis [4]. Surgery remains the major approach for the treatment of localized ccRCC; novel therapeutic strategies are urgently needed for metastatic patients
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