Figure 5
CDA expression in MPM patient samples before neoadjuvant therapy was significantly associated with worse overall survival. (A) Example of a tumor center with a low basal CDA staining intensity that increased significantly after neoadjuvant therapy (sample 7522045; see also Fig. S3D). (B) Example of a tumor center with high basal CDA staining intensity that increased significantly after neoadjuvant therapy (sample 12678090; see also Fig. S3D). (C) Correlation analysis of CDA expression and survival in non-matched MPM samples before neoadjuvant therapy (p = 0.029, n = 57). (D) Correlation analysis of the relative changes in the expression of CDA and survival time in paired MPM tissue samples before and after therapy (p = 0.18, n = 28). (E) Schematic illustration of the concept of schedule-dependent, capecitabine-based therapy. In detail, tumors are composed of various cellular subsets, including cancer cells with shared genetic alterations. These cancer cells can be further divided into subpopulations, each characterized by distinct epigenetic programs, resulting in different states along the EMT spectrum. Standard chemotherapy, specifically the combination of cisplatin and MTA for lung cancer treatment, primarily eradicates cancer cells with an epithelial phenotype. In contrast, cancer cells with a more mesenchymal phenotype tend to be more resistant to this treatment. Additionally, chemotherapy induces EMT in a subset of cancer cells, causing some cells to newly acquire a resistant state. This mesenchymal/resistant state is associated with increased CDA expression, rendering these cells sensitive to capecitabine treatment.
