Prognostic and Immunoinfiltration Analysis of Transcription Factor BTF3 in Pan-cancer

BTF3, also known as BETA-NAC, BTF3b, BTF3a, and NACB, is a transcription factor originally isolated from HeLa cell extracts. It forms stable complexes with RNA polymerase II and plays a critical role in transcription initiation. Although aberrant BTF3 expression has been reported in certain malignancies, its overall role across diverse tumor types remains poorly defined. This study aimed to elucidate the functional implications of BTF3 across various cancers.

BTF3 expression was analyzed using datasets from The Cancer Genome Atlas (TCGA), including TCGA_GTEx, TCGA unpaired, and TCGA paired samples. The prognostic significance of BTF3 across 33 tumor types was evaluated using Kaplan-Meier survival and univariate Cox regression analyses. In cancers where BTF3 expression showed prognostic value, additional clinical correlation analyses were performed. Clear cell renal carcinoma (sample size >500) was selected for nomogram construction to illustrate BTF3's prognostic relevance. The association between BTF3 expression and immune cell infiltration was also examined, alongside functional enrichment analysis to explore involved signaling pathways.

BTF3 displayed variable expression across tumor types and was significantly correlated with several clinical parameters. Survival and regression analyses identified BTF3 as a prognostic marker in specific cancers. The nomogram model for clear cell renal carcinoma further supported its predictive value. BTF3 expression was also associated with features of the tumor immune microenvironment. Functional enrichment analysis implicated signaling pathways, including the tuberous sclerosis complex/mechanistic target of rapamycin (TSC/mTOR), phosphoinositide 3-kinase/AKT (PI3K/AKT), and rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) in BTF3-associated tumorigenesis.

These findings underscore the heterogeneous expression of BTF3 across malignancies and highlight its potential involvement in modulating the tumor immune landscape and oncogenic signaling pathways. The results expand our understanding of BTF3's role in cancer biology and suggest mechanistic links to well-characterized tumorigenic processes. However, further experimental validation is necessary to substantiate these associations.

BTF3 may serve as a promising prognostic biomarker and a potential target for immunotherapeutic intervention across multiple cancer types.