Transcriptomic Profiling of the Effects of DDR1 in Breast and Ovarian Cancer to Understand the Association Between DDR1 Expression and Patient Survival.

Background: Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase that plays an important role in epithelial cell regulation; its function in cancer appears to be dependent on tumour type. Methods: This study investigated DDR1 expression in large numbers of breast (n = 1416) and ovarian (n = 450) tumours using immunohistochemistry. In addition, RNA sequencing was conducted on DDR1 knockdown breast and ovarian cancer cell lines. Results: In breast cancer, high DDR1 expression was significantly associated with poor patient survival in ER-positive disease and low expression was associated with poor patient survival in ER-negative disease. In ovarian cancer, high DDR1 expression was associated with improved patient survival. In DDR1 knockdown IGROV1 ovarian cancer cells, 770 transcripts were differentially expressed, whilst in DDR1 knockdown T47D breast cancer cells, 3647 transcripts were differentially expressed. Only 149 genes were shared, suggesting that DDR1 drives distinct transcriptional programmes across cancer types. Shared genes between T47D and IGROV1 DDR1 knockdown cells include key regulators of signalling, metabolism, and cytoskeletal organisation such as YWHAE, NCK2, FN1, and ITGB4. Gene Ontology analysis revealed significant enrichment of epithelial cell migration pathways in both cell lines. Conclusions: Current protein expression and transcriptomic data highlight the important prognostic role of DDR1 expression in breast and ovarian cancer and provide hypothesis-generating insights into the contextual and transcriptomic differences between the two cancer types.