Frontiers in Bioinformatics
Pan-cancer multi-omics profiling of SRPK1 identifies tumour-specific associations with prognosis and predicted chemotherapy response in breast, colon and prostate cancer
By Duygu Duzgun and Sebastian Oltean.
Abstract
PurposeSerine/arginine-rich protein kinase 1 (SRPK1), a regulator of splicing-factor activity and alternative splicing, has been implicated in cancer progression and therapy resistance. However, the tumour-specific expression landscape and clinical relevance of SRPK1 across human cancers remain incompletely defined. This study aimed to investigate SRPK1 expression, prognostic relevance, and associations with predicted chemotherapy response through pan-cancer multi-omics profiling, with a focused evaluation in breast, colon, and prostate cancer.MethodsPublic transcriptomic, proteomic, immunohistochemical, survival, functional network and pharmacogenomic datasets were interrogated, including TCGA, GEPIA2, CPTAC/UALCAN, the Human Protein Atlas, GeneMANIA, STRING, GSCA and CPADS. SRPK1 mRNA and protein expression, survival associations, SRPK1-related splicing networks, SRPK1–SRSF1 co-expression and predicted drug-response associations were assessed in breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD) and prostate adenocarcinoma (PRAD) cohorts.ResultsSRPK1 displayed heterogeneous expression across TCGA tumour types, supporting tumour-specific dysregulation. SRPK1 mRNA and protein levels were increased in BRCA and COAD, whereas in PRAD, expression changes were more dataset-dependent. Survival analyses revealed cancer-type-dependent prognostic associations: high SRPK1 expression was associated with poorer outcomes in BRCA, whereas low SRPK1 expression was associated with poorer outcomes in COAD. SRPK1 was positively co-expressed with SRSF1 and mapped to splicing-related interaction networks. Pharmacogenomic analyses further linked SRPK1 expression to drug-sensitivity variation in cancer cell lines and to tumour-type-specific predicted chemotherapy response, including cisplatin in COAD and docetaxel in PRAD.ConclusionThese findings identify SRPK1 as a context-dependent molecular candidate associated with prognosis and predicted chemotherapy response in breast, colon and prostate cancer, supporting future experimental validation of SRPK1-linked splicing pathways in tumour-specific chemoresistance.



