The Transcriptional and Immunological Roles of Six2 in Clear Cell Renal Cell Carcinoma

Abstract

Background: Six2, a transcription factor, exerts an oncogenic role in clear cell renal cell carcinoma (ccRCC). Increased Six2 expression could enhance cancer metastasis. However, the regulatory mechanism of Six2 in promoting metastasis remains unclear. The purpose of this study is to analyze the regulatory pattern of Six2 and the potential role of Six2 in the tumor immune microenvironment. Materials and Methods: Firstly, transcriptional data in TCGA-KIRC cohorts was used to analyze the relationship between Six2 expression and clinical information. Secondly, we detect the association between Six2 and the tumor immune microenvironment in ccRCC. Then, we analyzed Six2-related differentially expressed genes (DEGs) and constructed a prognostic model using the Lasso-Cox algorithm by integrating Six2 ChIP data and co-expressed genes. Next, we analyzed the clinical significance and immunotherapy sensitivity of this model. Results: Six2 was overexpressed in RCC cells compared with normal kidney cells and upregulated Six2 was positively linked with clinical stage, grade, T stage, M stage, and poor survival. And Six2 was correlated with the remodeling of the tumor microenvironment. Potential downstream effectors and biological functions regulated by Six2 were identified using in silico analysis. Meanwhile, a risk model based on 8 Six2 target genes was established to classify ccRCC patients into high-and-low risk groups. This risk model showed a reliable ability to forecast the overall survival of ccRCC patients and predict the susceptibility to immunotherapy. Conclusions: Our findings provide a promising prognostic indicator for ccRCC patients and help better understand the transcriptional and immunological role of Six2 in ccRCC.