There have been reported many gene expression profile which can predict prognosis of early stage breast cancer. We have reported the TP53 signature which can predict dysfunction caused by TP53 gene mutation in transcriptome level, and the status defined by TP53 signature can predict more accurate prognosis of early stage breast cancer compare to the status defined by TP53 DNA sequence. Recently, TP53 signature was reported as robust predictor of early stage breast cancer by meta-analysis (BMC Cancer,2015). The aim of this study is to make clear the molecular feature of poor prognosis group diagnosed by TP53 signature and to make easy and quick diagnostic kit which can be used in clinical situation.
We have done RNA-seq analysis using Hiseq2500 (Illumina) and reanalyzed TCGA data of breast cancer to make clear molecular feature of poor prognosis group defined by TP53 signature. We made simple diagnostic kit using nCounter (Nanostring technology). Using this simple diagnostic kit, we diagnosed 234 breast cancer sample as TP53 signature mutant or TP53 signature wild, and we proved robust prediction power of TP53 signature for early stage breast cancer. We used RNA-seq data to compare prediction power of TP53 signature to Mammaprint, OncotypeDX, TP53 structural mutation.
TP53 signature mutant group have structural mutation in genes, including BRCA1, BRCA2, Rb1 except for TP53, which function is gene repair. In addition, TP53 signature mutant group shows high expression of PD-L1, high mutation burden and high copy number alternation. Analysis of 190 stage I-II breast cancer patients shows TP53 signature by simple diagnostic kit using nCounter has strong prediction power compare to Mammaprint, OncotypeDX, TP53 structural mutation, and clinical factors.
We have developed TP53 signature as diagnostic system for early stage breast cancer which is useful in clinical situation. Poor prognosis group diagnosed by TP53 signature shows molecular features which overlap good response marker of immune-check point inhibitors.
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All authors have declared no conflicts of interest.