Using Elevated Cholesterol Synthesis as a Prognostic Marker in Wilms' Tumor: A Bioinformatic Analysis

BACKGROUND: Wilms tumor is the most common renal malignancy of children. Identifying factors that could predict the prognosis of patients with Wilms tumor is clinically meaningful. Many studies found tumors with elevated cholesterol synthesis that are featured with dismal prognosis. Even in some clinical trials, people with excessive dietary cholesterol intake and high plasma low-density lipoprotein levels are observed to have increased risk for cancer. However, the role of cholesterol biosynthesis in Wilms tumor has not yet been well clarified. METHODS: RNA sequencing transcriptome data and all corresponding clinicopathological information used in our study were downloaded from the TARGET database. High-throughput sequencing (Fragments Per Kilobase of transcript per Million fragments mapped) data sets of 130 tumor samples and 6 normal samples were obtained for further analysis. RESULTS: Wilms tumor samples with higher activity of cholesterol synthesis are characterized with worse overall survival (P < 0.05). In addition, Wilms tumor samples with mitigated activity of cholesterol synthesis are featured with better dendritic cell (DC) function and cytolytic activity (P < 0.05). Furthermore, we constructed a prognosis model based on differential expressed cholesterol synthesis-related genes (DECSG), which could predict the OS of patients with Wilms tumor accurately. KEGG and GO analysis of differential expressed genes between tumor samples with high and low cholesterol synthesis indicated that DECSGs are highly enriched in “mitosis nuclear division,” “nuclear division,” “chromosome segregation,” “cell cycle,” “Spliceosome,” and “RNA transport.” CONCLUSIONS: In conclusion, our study reported increased cholesterol synthesis in Wilms tumor predicts a worse prognosis and mitigated cytolytic activity, DC function, and MHC I signature in the tumor microenvironment. We also constructed a prognosis model for predicting the OS of patients with good accuracy, which is promising in clinical translation. Future studies should focus on the detailed mechanism that caused increasing cholesterol which promotes tumor progression and undermines patients' survival.