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

Yang Fu; Shanshan Sun; Xiaojun Man; Chuize Kong

doi:10.7717/peerj.7854

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

PeerJ. 2019 Oct 2:7:e7854. doi: 10.7717/peerj.7854. eCollection 2019.

Authors

Yang Fu^{1

2}, Shanshan Sun^{2

3}, Xiaojun Man^{1

2}, Chuize Kong^{1

2}

Affiliations

¹ Departments of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
² China Medical University, Shenyang, Liaoning, China.
³ Departments of Pharmacy, The First Hospital of China Medical University, Shenyang, Liaoning, China.

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.

Keywords: Clear cell renal cell carcinoma; GSEA; Prognosis; RUNX1; TCGA.

Grants and funding

This work was supported by the Project of Liaoning Distinguished Professor (Grant No. [2012]145), the Shenyang Plan Project of Science and Technology (Grant No. F17-230-9-08), China Medical University’s 2017 Discipline Promotion Program (Grant No. 3110117040), China Medical University’s 2018 Discipline Promotion Program, and the 2017 National Key R&D Program Key Projects of Precision Medical Research (No. 2017YFC0908000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.