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

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)...

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Main Authors: Yang Fu, Shanshan Sun, Xiaojun Man, Chuize Kong
Format: Article
Language:English
Published: PeerJ Inc. 2019-10-01
Series:PeerJ
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Online Access:https://peerj.com/articles/7854.pdf
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author Yang Fu
Shanshan Sun
Xiaojun Man
Chuize Kong
author_facet Yang Fu
Shanshan Sun
Xiaojun Man
Chuize Kong
author_sort Yang Fu
collection DOAJ
description 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.
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spelling doaj.art-45c606f9366a406d8684722669e464ea2023-12-03T06:49:15ZengPeerJ Inc.PeerJ2167-83592019-10-017e785410.7717/peerj.7854Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosisYang Fu0Shanshan Sun1Xiaojun Man2Chuize Kong3Departments of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaChina Medical University, Shenyang, Liaoning, ChinaDepartments of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartments of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaBackground 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.https://peerj.com/articles/7854.pdfClear cell renal cell carcinomaRUNX1PrognosisGSEATCGA
spellingShingle Yang Fu
Shanshan Sun
Xiaojun Man
Chuize Kong
Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
PeerJ
Clear cell renal cell carcinoma
RUNX1
Prognosis
GSEA
TCGA
title Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
title_full Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
title_fullStr Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
title_full_unstemmed Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
title_short Increased expression of RUNX1 in clear cell renal cell carcinoma predicts poor prognosis
title_sort increased expression of runx1 in clear cell renal cell carcinoma predicts poor prognosis
topic Clear cell renal cell carcinoma
RUNX1
Prognosis
GSEA
TCGA
url https://peerj.com/articles/7854.pdf
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AT xiaojunman increasedexpressionofrunx1inclearcellrenalcellcarcinomapredictspoorprognosis
AT chuizekong increasedexpressionofrunx1inclearcellrenalcellcarcinomapredictspoorprognosis