Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis

Abstract

Background Runt-related transcription factor 1 (RUNX1) was previously reported to play a dual role in promoting or suppressing tumorigenesis in various malignancies. A public dataset from The Cancer Genome Atlas (TCGA) was used to evaluate the role of RUNX1 in clear cell renal cell carcinoma (ccRCC). Methods The Wilcoxon signed-rank test was used to compare the expression of RUNX1 in ccRCC tissues and normal tissues. The Wilcoxon signed-rank test and logistic regression were utilized to investigate the relationship between clinicopathological factors and RUNX1 expression. Additionally, we analysed the differences in prognosis between patients with high and low expression of RUNX1 via the Kaplan–Meier method and Cox regression. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms of RUNX1 in ccRCC. Results The expression of RUNX1 in ccRCC tissues was significantly higher than that in normal tissues. High expression of RUNX1 was significantly associated with gender (p = 0.003), clinical stage (p < 0.001), tissue infiltration (p < 0.001), lymph node metastasis (p = 0.037) and histological grade (p < 0.001). Logistic regression analysis showed that high RUNX1 expression was significantly correlated with gender (OR = 1.71 for male vs. female, p = 0.004), histological grade (OR = 11.61 for grade IV vs. I, p < 0.001), clinical stage (OR = 1.55 for stage III/IV vs. I/II, p = 0.014) and tissue infiltration (OR = 1.54 for positive vs. negative, p = 0.018). Kaplan–Meier survival curves revealed that the prognosis of patients with ccRCC with high RUNX1 expression was worse than that of patients with ccRCC with low RUNX1 expression (p < 0.001). Univariate Cox regression analysis showed that high RUNX1 expression was strongly correlated with poor prognosis (HR = 1.60, 95% CI [1.31–1.97], p < 0.001). In addition, high expression of RUNX1 was an independent prognostic factor for poor overall survival (OS), with an HR of 1.50 (95% CI [1.20–1.87], p < 0.001) in multivariate Cox analysis. GSEA showed that the apoptosis, B cell receptor signalling pathway, calcium signalling pathway, chemokine signalling pathway, JAK/STAT signalling pathway, MAPK signalling pathway, p53 signalling pathway, pathways in cancer, T cell receptor signalling pathway, Toll-like receptor signalling pathway, VEGF signalling pathway, and Wnt signalling pathway were significantly enriched in the RUNX1 high-expression phenotype. In conclusion, RUNX1 can be used as a novel prognostic factor and therapeutic target in ccRCC.

RUNX1 Is a Driver of Renal Cell Carcinoma Correlating with Clinical Outcome

“…Kaplan-Meier survival analysis of the ccRCC patients with RUNX1 mRNA upregulation shows that they have a statistically significant decrease in survival compared to the unaltered cohort (Log-rank P=0.0008, RUNX1 Unaltered median=76.98 months, RUNX1 mRNA upregulation median=36.21 months) ( Supplementary Fig1c). This is in line with a recent report interrogating the TCGA dataset (35). Furthermore, data obtained using the pan-cancer RNA-seq KM plotter (36) tool analysing clinical survival data from 530 ccRCC patients also show that high RUNX1 expression correlates with poorer overall survival (P<0.0001), ( Supplementary Fig1d).…”

lncRNA TTN‑AS1 upregulates RUNX1 to enhance glioma progression via sponging miR‑27b‑3p

“…For example, RUNX1 was inhibited by miR-106a-5p, thereby enhancing osteosarcoma tumorigenesis ( 29 ). RUNX1 was observed to be increased in renal cell carcinoma and was associated with poor prognosis ( 30 ). Keita et al identified RUNX1 as a tumor promotor in ovarian cancer and skin cancer ( 31 ).…”

Expression Patterns and Prognostic Value of RUNX Genes in Kidney Cancer

“…Increasingly, it has been implicated in cancers of ovary [30] , prostate [31] and stomach [32] , which was associated with either gain or loss of RUNX1 function. Recently, Yang et al revealed that higher RUNX1 expression may be associated with poorer survival in RCC [33] ; this was later confirmed by Rooney et al who utilized a genetically engineered mouse (GEM) model [18] .…”