Research Paper Volume 12, Issue 9 pp 8484—8505

Identification of transforming growth factor beta induced (TGFBI) as an immune-related prognostic factor in clear cell renal cell carcinoma (ccRCC)

Guo-Wei Du 1, , Xin Yan 1, , Zhao Chen 1, , Ren-Jie Zhang 1, , Kurerban Tuoheti 1, , Xiao-Jie Bai 1, , Hua-Hui Wu 1, , Tong-Zu Liu 1, ,

  • 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

received: October 29, 2019 ; accepted: April 16, 2020 ; published: May 14, 2020 ;

https://doi.org/10.18632/aging.103153
How to Cite

Copyright © 2020 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among kidney cancer, which has poor prognosis. The aim of this study was to screen out novel prognostic biomarkers and therapeutic targets for immunotherapy, and some novel molecule drugs for ccRCC treatment. Immune scores ranged from -1109.36 to 2920.81 and stromal scores ranged from -1530.11 to 1955.39 were firstly calculated by applying ESTIMATE algorithm. Then 17 DEGs associated with immune score and stromal score were further identified. 6 candidate hub genes were screened out by performing overall survival (OS) and disease-free survival analyses based on TCGA-KIRC data, one of which including TGFBI was further regarded as hub gene associated with prognosis by calculating the R2 (R2 = 0.011, P = 0.018) and AUC (AUC = 0.874). The prognostic value of TGFBI was validated by performing OS, CSS, and PFS analyses based on GSE29609 and E-MTAB-3267. CMap analysis suggested that 3 molecule drugs might be novel choice for ccRCC treatment. Further analysis demonstrated that CNVs of TGFBI was associated with OS of patients with ccRCC. TGFBI expression was also correlated with histologic grade, pathologic stage, and immune infiltration level, significantly. TGFBI was the most relevant gene with OS among the candidate hub genes, which might be novel DNA methylation biomarkers for ccRCC. In conclusion, our findings indicated that TGFBI was correlated with prognosis of patients with ccRCC, which might be novel prognostic biomarkers, and targets for immunotherapy in ccRCC. Three small molecule drugs were also identified, which showed strong potential for ccRCC treatment.

Abbreviations

ANOVA: Analysis of Variance; AUC: area under curve; BP: biological process; C1R: complement C1r; C1S: complement C1s; CC: cellular component; CCLE: cancer cell line encyclopedia; ccRCC/KIRC: Clear cell renal cell carcinoma; CMap: Connectivity map; CNV: copy number variation; CSS: cancer specific survival; DAVID: Database for Annotation, Visualization, and Integrated Discovery; DEGs: Differentially expressed genes; DFS: Disease-free survival; EMT: epithelial-mesenchymal transformation; ESTIMATE: Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data; FDR: False discovery rate; GO: Gene ontology; GEO: Gene expression omnibus; GEPIA: Gene Expression Profiling Interactive Analysis; GSEA: Gene set enrichment analysis; IARC: the International Agency for Research on Cancer; KEGG: Kyoto encyclopedia of genes and genomes; MF: molecular function; OS: Overall survival; PFS: progression free survival; RCC: renal cell carcinoma; ROC: receiver operating characteristic; TCGA: The Cancer Genome Atlas; TGFBI: transforming growth factor beta induced; TME: tumor microenvironment; TOM: Topological overlap matrix; WHO: World Health Organization.