1. Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, Guangxi Zhuang Autonomous Region, P.R. China, 530021.
2. Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China. 530021 (Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China, 530021).
Background: The most frequent primary bone cancer in teenagers, osteosarcoma (OS), is particularly aggressive with a high mortality rate.
Methods: By combining public databases, OS and non-cancer samples were obtained. The Wilcoxon test and standardized mean difference (SMD) were utilized to evaluate the mRNA expression level of TATA-box binding protein associated factor, RNA polymerase 1 subunit D (TAF1D). The potential of TAF1D to discriminate OS samples from non-cancer samples was revealed by summary receiver operating characteristic curve (sROC). To investigate the prognostic significance, Kaplan‒Meier curve and univariate Cox analysis were performed. Immunohistochemistry (IHC) was used to determine the TAF1D protein expression level. ESTIMATE algorithm and TIMER2.0 database were used to reveal the association between TAF1D expression and the immune microenvironment. Enrichment analysis and potential drug prediction were performed to clarify the underlying molecular mechanisms and possible therapeutic directions of TAF1D. Ultimately, the transcription factors (TFs) and the TAF1D binding site were predicted based on the Cistrome and JASPAR databases.
Results: TAF1D was upregulated in OS at the mRNA and protein levels and possessed robust discriminatory power. TAF1D upregulation was suggestive of worse prognosis and enhancement of tumor purity in OS patients. The cell cycle was the most significantly enriched pathway, and NU.1025 was considered to be the potential target agent. Finally, MYC was identified as a TF that regulates the expression of TAF1D.
Conclusions: Altogether, TAF1D has the potential to serve as a biological marker and therapeutic target in OS, which could offer new perspectives for OS treatment.
Keywords: TATA-box binding protein associated factor, RNA polymerase Ⅰ subunit D (TAF1D), osteosarcoma, clinical significance, biomarker.