1. Assessment of SWI/SNF chromatin remodeling complex related genes as potential biomarkers and therapeutic targets in pan-cancer.
- Author
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Zhuang K, Wang L, Lu C, Liu Z, Yang D, Zhong H, Zou J, Fahira A, Wang J, and Huang Z
- Subjects
- Humans, Prognosis, Mutation, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Transcription Factors genetics, Transcription Factors metabolism, Molecular Targeted Therapy, Gene Expression Profiling, Biomarkers, Tumor genetics, Chromatin Assembly and Disassembly, Gene Expression Regulation, Neoplastic drug effects, Neoplasms genetics, Neoplasms drug therapy, Neoplasms pathology, Neoplasms metabolism
- Abstract
Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy., (© 2024. The Author(s).)
- Published
- 2024
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