Expression of Platelet-derived growth factor-CC (PDGF-CC) is associated with the TNBC (triple-negative breast cancer) subtype. We have previously reported paracrine PDGF-CC signaling to be of importance for maintaining TNBC tumor cell phenotype.
We aimed to characterize PDGF-CC expression within the TNBC patient population by combining studies of PDGF-CC in tissue microarrays (TMAs) with matching RNA-Seq data and clinical follow-up; all variables originating from the SCAN-B (Sweden Cancerome Analysis Network – Breast) clinical study (NCT02306096). TMAs constructed of primary TNBC patient samples (N=254) were stained for PDGF-CC using the Dako PT Autostainer system. Tumor cell-specific expression of PDGF-CC intensity was scored as either absent (N=11), weak (N=86), intermediate (N=81) or strong (N=70).
Intermediate and strong PDGF-CC scores were associated with Nottingham Histological Grade 3 (p=0.001), increased Ki-67 percentage (p<0.001) and younger patient age at diagnosis (p=0.002). RNA-Seq data corresponding to tumors included in the TMAs were retrieved and Gene Set Enrichment Analysis (GSEA) was performed, comparing the TMA-derived PDGF-CC subgroups. Immune-related signatures were found to be enriched in the strong PDGF-CC subgroup vs. intermediate. Interestingly, strong PDGF-CC intensity was associated with a decreased risk of recurrence in the chemotherapy treated patient group (HR 0.28, 95% CI 0.10-0.80, p=0.017, univariate Cox regression). Finally, patient samples were assigned a PAM50 subtype and a TNBC molecular subtype (Lehmann et al 2011). Ninety-four percent of tumors in the strong PDGF-CC subgroup were classified as basal-like, whereas the corresponding number in the weak and intermediate PDGF-CC subgroups were 51% and 84%, respectively.
In conclusion, strong PDGF-CC protein expression identified basal-like TNBCs, with an increase in immune cell infiltrate shown by RNA-Seq analysis. Based on the work, a window-of-opportunity trial (NCT05722795) has been launched to examine the effect of PDGF-CC inhibition on TNBC phenotype.
Lund University.
Lund University and The Swedish Cancer Society.
A. Bosch: Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Lilly; Financial Interests, Personal, Member of the Board of Directors: SACRA Therapeutics. K. Pietras: Financial Interests, Personal, Stocks/Shares: Paracrine Therapeutics. All other authors have declared no conflicts of interest.