We aimed to identify the factors affecting the successful
tumor engraftment in
breast cancer patient-derived xenograft (PDX) models. Further, we investigated the prognostic significance and the functional importance of the PDX engraftment-related genes in
triple-negative breast cancers (TNBC). The clinico-pathologic features of 81
breast cancer patients whose tissues were used for PDX
transplantation were analyzed to identify the factors affecting the PDX engraftment. A gene signature associated with the PDX engraftment was discovered and its clinical importance was tested in a publicly available dataset and in vitro assays. Nineteen out of 81 (23.4 %) transplanted
tumors were successfully engrafted into the PDX models. The engraftment rate was highest in TNBC when compared to other subtypes (p = 0.001) and in recurrent or
chemotherapy-resistant
tumors compared to newly diagnosed primary
tumors (p = 0.024). PDX
tumors originated from the TNBC cases showed more rapid
tumor growth in mice. Gene expression profiling showed that down-regulation of genes involved in the
tumor-immune interaction was significantly associated with the successful PDX engraftment. The engraftment gene signature was associated with worse survival outcome when tested in publicly available
mRNA datasets of TNBC cases. Among the engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in
triple-negative breast cancer cell lines, and
siRNA-based gene silencing resulted in reduced cell invasion and proliferation in vitro. Our results show that the PDX engraftment may reflect the aggressive phenotype in
breast cancer. Genes associated with the PDX engraftment may provide a novel prognostic
biomarker and therapeutic targets in TNBC.