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

• Published in: Aging (Albany, NY.) Vol. 12; no. 9; pp. 8484 - 8505
• Main Authors: Du, Guo-Wei, Yan, Xin, Chen, Zhao, Zhang, Ren-Jie, Tuoheti, Kurerban, Bai, Xiao-Jie, Wu, Hua-Hui, Liu, Tong-Zu
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 14-05-2020
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - pathology; Disease-Free Survival; DNA Methylation; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - immunology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Gene Regulatory Networks - immunology; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - immunology; Kidney Neoplasms - pathology; Male; Prognosis; Research Paper; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - immunology; DNA methylation; prognostic biomarkers; clear cell renal cell carcinoma; tumor immune microenvironment; copy number variations
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.103153

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 R
(R
= 0.011,
= 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.