Clinical Implications of SRPK1 Expression in Human Tumours: A Comprehensive Pan-Cancer Analysis Based on Multi-Omics Databases

Abstract

Serine/arginine-rich protein kinase 1 (SRPK1), which primarily regulates alternative splicing (AS), has been implicated in various malignancies. However, the comprehensive expression landscape and clinical relevance of SRPK1 across diverse tumour types have not been systematically investigated. Chemoresistance remains a formidable obstacle in cancer treatment, accounting for nearly 90% of treatment failures and leading to poor patient survival. Aberrant AS, often driven by splicing factors like SRPK1, is a mechanism cancer cells exploit to overcome chemotherapy-induced cytotoxicity. With that, this study tested the hypothesis of tumour-specific alterations in SRPK1 expression as novel therapeutic targets through a pan-cancer analysis of SRPK1 using multi-omics data, obtained from public databases, including TCGA, CPTAC, GEPIA2, and drug sensitivity platforms. The analysis specifically assessed the pan-cancer expression landscape of SRPK1 at the mRNA and protein levels and its prognostic implications across different cancer types (breast, colon, and prostate cancers), functional analysis of SRPK1-associated splicing network, and its expression in correlation with predicted drug sensitivity. The results revealed the correlations of high SRPK1 expression with worse overall and disease-free survival in a cancer-specific manner and resistance to standard-of-care agents like cisplatin and docetaxel. The integrative multi-omics approach in this study provided a robust foundation for understanding the complex, multifaceted role of SRPK1 in tumour-specific chemoresistance.