Abstract
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies, and once metastasis occurs, it often has a poor prognosis and lacks effective treatment. Therefore, there is an urgent need to screen some new biomarkers and explore their molecular mechanisms to improve the early clinical diagnosis and targeted therapy of ccRCC. SPOCK1 (SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1) is a conserved multi-domain proteoglycan that plays an important role in the development of multiple cancer types; however, its prognostic value in ccRCC has not been investigated. The study of the prognostic value of SPOCK1 in ccRCC is a good complement to the study of ccRCC biomarkers. METHODS: Databases of this study included Oncomine, Kaplan-Meier Plotter, GEPIA, GeneMANIA, cBioPortal, and TIMER. Student's t-test was used to analyze the differences in SPOCK1 expression in ccRCC tissues compared with tumor-adjacent normal tissues. Kaplan-Meier curves for survival analysis were used to assess the correlation between the expression of SPOCK1 and the prognostic outcomes. Correlation module drew the expression scatterplots between SPOCK1 and immune cell infiltration in ccRCC, together with the Spearman's rho value and estimated statistical significance. RESULTS: The SPOCK1 mRNA expression was significantly higher in ccRCC tissues (mean expression ± SD: 920.2±195.2) than in normal tissues (mean expression ± SD: 358.4±29.1, P=0.008), and high SPOCK1 expression significantly and positively correlated with the pathological stage of ccRCC patients (F value =10.2, P<0.001). Higher expression of SPOCK1 was also associated with significantly shorter overall survival (OS) and disease-free survival (DFS) in ccRCC patients (GEPIA: P=0.046, P<0.001, respectively; Kaplan-Meier Plotter: P=0.002, P=0.0022, respectively). The function of SPOCK1 is mainly related to tumor development and extracellular matrix remodeling, and it may participate in the epithelial-mesenchymal transition process. SPOCK1 expression significantly and positively correlated with infiltration of several immune cells in ccRCC, including cancer-associated fibroblasts (CAFs) (Rho =0.333, P=2.16×10(-13)), tumor-associated macrophages (TAMs) (Rho =0.18, P=1.02×10(-4)), and tumor-associated neutrophils (TANs) (Rho =0.165, P=3.83×10(-4)). Conversely, there was a significant and negative correlation between SPOCK1 expression and infiltration of CD4(+) T cells (Rho =-0.113, P=0.015). CONCLUSIONS: SPOCK1 may be a potential prognostic biomarker in ccRCC.