TP53 signature score predicts prognosis and immune response in triple-negative breast cancer

Abstract Purpose Triple-negative breast cancer (TNBC) is considered a heterogeneous population and achieving a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is an only prognostic factor. Previously, the TP53 signature (TP53sig)-score, an expression profile of 33 genes, is reportedly predictive of the prognosis of all types of early-stage breast cancer. Herein, we analyzed whether the TP53sig-score can be subclassified in detail with only a TNBC cohort and investigated the molecular biological characteristics of the higher TP53sig-score. Methods Publicly available data from TCGA(RNA-sequence) and METABRIC (microarray) and real clinical specimens’ s expression data (NanoString Technologies) were used to explore the prognosis and molecular features of TNBC. Results The high TP53sig-score group in the present study and the cohort in METABRIC tended to have a worse prognosis than the low TP53sig-score group (p=0.583 and 0.196, respectively). In both the pCR and non-pCR groups, the high TP53sig-score patients tended to have a poor prognosis (p=0.0739). Moreover, when the NAC response and TP53sig-score were combined, the five-year breast cancer-free rate among the four groups differed significantly (p=0.043). In addition, high TP53sig-score was related to gene ontology terms, such as “cell differentiation” and “innate immune response. Notably, this group had the potential to respond favorably to immunotherapy according to the tumor immune dysfunction and exclusion model. Conclusion Combining the response to NAC and the TP53sig-score in triple-negative breast cancer was able to predict an unfavorable prognosis. Further, patients with a high TP53sig-score showed a favorable feature associated with immunotherapy