Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Serine/arginine-rich splicing factors (SRSFs) are key regulators of RNA splicing and play significant roles in cancer development.
• Dysregulation of SRSFs is implicated in various cancers, suggesting their potential as therapeutic targets.
• A comprehensive understanding of SRSF molecular characteristics, mechanisms, and clinical relevance across diverse human cancers is lacking.

Purpose of the Study:

• To conduct a systematic analysis of SRSFs' molecular characteristics and clinical implications in a large cohort of human cancers.
• To investigate the association of SRSFs with cancer immunity, patient survival, and response to cancer therapies.

Main Methods:

• Systematic analysis of SRSF genomic alterations and expression patterns.
• Investigation of DNA methylation, m6A modification, and miRNA regulation of SRSFs.
• Correlation analysis of SRSFs with cancer immunity, survival data, and drug sensitivity across 33 cancer types (>10,000 samples).

Main Results:

• SRSFs exhibit prevalent genomic alterations and expression perturbations across multiple cancer types.
• SRSF regulation via DNA methylation, m6A, and miRNA is cancer-specific.
• SRSFs are significantly associated with cancer immunity, predict immunotherapy response, and are prognostic for patient survival.
• SRSFs indicate sensitivity to targeted therapy and chemotherapy.

Conclusions:

• SRSFs are integral to cancer occurrence and progression, exhibiting diverse molecular alterations.
• SRSFs serve as robust biomarkers for predicting immunotherapy response, patient survival, and drug sensitivity.
• Targeting SRSFs offers a promising avenue for developing novel cancer therapeutic strategies.