Abstract
Clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of renal cell carcinoma (RCC) and has a poor 5-year survival rate. In recent years, medical advancement has promoted the understanding of the histopathological and molecular characterization of ccRCC; however, the carcinogenesis and molecular mechanisms of ccRCC remain unclear. Chromatin accessibility is an essential determinant of cellular phenotype. This study aimed to explore the potential role of chromatin accessibility in the development and progression of ccRCC. By the combination of open-access genome-wide chromatin accessibility profiles and gene expression profiles in ccRCC, we obtained a total of 13,474 crucial peaks, corresponding to 5,120 crucial genes and 9,185 differentially expressed genes. Moreover, two potential function modules (P2 and G4) that contained 129 upregulated genes were identified via the weighted gene co-expression network analysis (WGCNA). Furthermore, we obtained five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT), and a prognostic model was established based on these genes through the least absolute shrinkage and selection operator-proportional hazards model (LASSO-Cox) analysis. This model can stratify the ccRCC samples into a high-risk and a low-risk group, from which the patients have distinct prognosis. Further analysis demonstrated a completely different immune cell infiltration pattern between these two risk groups. This study also suggested that mast cell resting is associated with the prognosis of ccRCC and could be a target of immunotherapy. Overall, this study indicated that chromatin accessibility plays an essential role in ccRCC. The five prognostic chromatin accessibility biomarkers and the prognostic immune cells can provide a new direction for the treatment of ccRCC.
Highlights
Renal cell carcinoma (RCC) is among the top 10 most common lethal malignant renal tumors in adults, and clear cell renal cell carcinoma accounts for 75%–85% of RCC [1]
The model is as follows: Risk score = 0:2555ExpFSCN1+0:1725ExpSLC17A9 +0:3769ExpANKRD13BÀ0:1930ExpADCY 2. According to this prognostic model, we found that FSCN1, SLC17A9, and ANKRD13B are oncogenes, and overexpression of these genes represents a poor prognosis, whereas ADCY2 and MAPT are tumor suppressor genes and associated with a better prognosis of Clear cell renal cell carcinoma (ccRCC)
After the LASSOCox analysis, we identified five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT) to construct a prognostic model, which can recognize the genome difference among patients with ccRCC and divide these patients into the high-risk and the low-risk groups
Summary
Renal cell carcinoma (RCC) is among the top 10 most common lethal malignant renal tumors in adults, and clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of RCC [1]. Most ccRCC cases are resistant to chemotherapy and radiotherapy, most likely due to their complicated molecular mechanisms. Surgical excision is still the main treatment. Metastasis occurs in 30% of patients leading to poor 5-year survival rates [2]. Identification and surgical treatment are beneficial for an optimistic prognosis. The underlying molecular mechanisms of ccRCC remain ambiguous and effective therapeutic targets are lacking. It is urgent to investigate the molecular mechanism and identify genes that are responsible for the carcinogenesis of ccRCC
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