Identification Of Spliceosome Components Pivotal To Breast Cancer Survival

Cancer cells employ alternative splicing (AS) to acquire splicing isoforms favouring their survival. However, the causes of aberrant AS in breast cancer are poorly understood. In this study, the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) data were analysed with univariate feature selection. Of 122 analysed spliceosome components,U2SURP, PUF60, DDX41, HNRNPAB, EIF4A3, andPPIL3were significantly associated with breast cancer survival. The top 4 four genes,U2SURP, PUF60, DDX41, andHNRNPAB, were chosen for further analyses. Their expression was significantly associated with cancer molecular subtype, tumour stage, tumour grade, overall survival (OS), and cancer-specific survival in the METABRIC data. These results were verifiable using other cohorts. The Cancer Genome Atlas data unveiled the elevated expression ofPUF60, DDX41, andHNRNPABin tumours compared with the normal tissue and confirmed the differential expression of the four genes among cancer molecular subtypes, as well as the associations ofU2SURP, PUF60, andDDX41expression with tumour stage. A meta-analysis data verified the associations ofU2SURP, PUF60, andHNRNPABexpression with tumour grade, the associations ofPUF60, DDX41, andHNRNPABexpression with OS and distant metastasis-free survival, and the associations ofU2SURPandHNRNPABexpression with relapse-free survival. Experimentally, we demonstrated that inhibiting the expression of the four genes separately suppressed cell colony formation and slowed down cell growth considerably in breast cancer cells, but not in immortal breast epithelial cells. In conclusion, we have identifiedU2SURP, PUF60, DDX41, andHNRNPABare spliceosome-related genes pivotal for breast cancer survival.