Project description:Cancer stem cells have an important role in tumour biology. While their identity in haematological malignancies is clearly defined, stem cell identity remains elusive in some solid tumours. Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer, but the identity or existence of ccRCC stem cells remains unknown. We aimed to discern their existence using the widely utilised side population approach in ccRCC cell lines. In all cells tested, a well-defined side population was identified, and cell-based assays suggested stem-like properties. However, limiting dilution assays revealed comparable tumour initiating abilities and tumour histology of side and non-side populations, and single cell RNA-sequencing revealed minimal differences between these populations. The results indicate that the side population approach is not sufficient for cancer stem cell discovery in ccRCC.
Project description:Clear cell renal carcinoma (CCRC) accounts for >80% of all kidney cancers but what triggers the tumorigenesis in the kidney and metastases in the bones are still under debate. Our hypothesis is that remodeling of the genomic fabrics of certain functional pathways and their interplay beyond critical limits are key causes of CCRC. We profiled the transcriptomes of metastatic chest wall and of two primary cancerous sites of the renal medulla and compared them with that of non-cancerous kidney resection margins. Samples were collected from a 74 years old male with metastatic carcinoma, consistent with renal cell carcinoma, clear cell type, Fuhrman grade 3, who undergone total right kidney nephrectomy and resection of a chest wall mass. Transcriptomic analysis pointed the tumor region in the right kidney that led to the chest wall metastases. The tumor proved heterogeneous not only in the expression level but also in the expression control, coordination and interplay of pathways responsible for cellular processes and genetic and environmental information processing. The differently regulated pathways in the two sides of the tumor: CCRC, and HIF-1, Vegfa and mTor signaling indicate activation of distinct mechanisms. Four-conditions (CTR = control - non-cancerous kidney resection margins, PTA = primary tumor side A, PTB = primary tumor side B, MET = chest wall metastasis. Four biological replicates of each condition.
Project description:To understand the relationship of radiomic and transcriptomic features of metastatic clear cell renal cell carcinoma, we performed RNA-sequencing in clear cell renal cell carcinomas (ccRCCs).
Project description:Background: Clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC) can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common. Method: To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA) containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed. Results: Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC) and CD9 (positive in chRCC) best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%. Conclusions: Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Stage of Clear Cell renal cell carcinoma (I - V)) disease_state_design
Project description:To investigate the function of ANGPTL8 in clear cell renal cell carcinoma, Caki-1 cells overexpressing ANGPTL8 and ANGPTL8 knockout were established.