TP53 Signature Score Predicts Prognosis and Immune Response in Triple-negative Breast Cancer

Abstract

Background/aim: Triple-negative breast cancer (TNBC) is considered a heterogeneous disease and achieving a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is considered a surrogate biomarker of a favorable prognosis. Previously, the TP53 signature (TP53sig)-score, the expression profile of 33 genes, has been reported to predict the prognosis of all types of early-stage breast cancer. Herein, we analyzed whether the TP53sig-score can be used to subclassify a TNBC cohort and investigated the molecular biological characteristics of the higher TP53sig-score.

Patients and methods: Publicly available data from TCGA (RNA-sequence) and METABRIC (microarray) and expression data from real clinical specimens (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: The combination of the response to NAC and the TP53sig-score in TNBC was able to predict an unfavorable prognosis. Furthermore, patients with a high TP53sig-score showed a favorable response to immunotherapy.

Keywords: Triple-negative breast cancer; gene signature; tumor immunity.