TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer:a clinical next-generation sequencing study

Background:TP53 mutations and homologous recombination deficiency(HRD)occur frequently in breast cancer.However,the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not clear.Methods:Clinical next-generation sequencing(NGS)of both tumor and paired blood DNA from 119 breast cancer patients(BRCA-119 cohort)was performed with a 520-gene panel.Mutations,tumor mutation burden(TMB),and genomic HRD scores were assessed from NGS data.NGS data from 47 breast cancer patients in the HRD test cohort were analyzed for further verification.Results:All TP53 pathogenic mutations in patients had somatic origin,which was associated with the protein expression of estrogen receptor and progestogen receptor.Compared to patients without TP53 pathologic mutations,patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic alterations.The frequency of TP53 pathologic mutation was higher in the HRDhigh group(HRD score≥42)relative to that in the HRD-low group(HRD score<42).TP53 has different mutational characteristics between the HRD-low and HRD-high groups.TP53-specific mutation subgroups had diverse genomic features and TMB.Notably,TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an area under the curve(AUC)of 0.61.TP53-specific mutations,namely HRD-low mutation,HRD-high mutation,and HRD common mutation,predicted the HRD status of breast cancer patients with AUC values of 0.32,0.72,and 0.58,respectively.Interestingly,TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values(0.80)in predicting HRD status.Conclusions:TP53-specific mutation combinations predict the HRD status of patients,indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase(PARP)inhibitors in breast cancer patients.

ZIF-8/LiFePO4 derived Fe-N-P Co-doped carbon nanotube encapsulated Fe2P nanoparticles for efficient oxygen reduction and Zn-air batteries

Iron-based oxygen reduction reaction(ORR)catalysts have been the focus of research,and iron sources play an important role for the preparation of efficient ORR catalysts.Here,we successfully use LiFePO4 as ideal sources of Fe and P to construct the heteroatom doped Fe-based carbon materials.The obtained Fe-N-P co-doped coral-like carbon nanotube arrays encapsulated Fe2P catalyst(C-ZIF/LFP)shows very high half-wave potential of 0.88 V in alkaline electrolytes toward ORR,superior to Pt/C(0.85 V),and also presents a high half-wave potential of 0.74 V in acidic electrolytes,comparable to Pt/C(0.8 V).When further applied into a home-made Zn-air battery as cathode,a peak power density of 140 mW·cm^-2 is reached,exceeds commercial Pt/C(110 mW·cm^-2).Besides,it also presents exceptional durability and methanol resistance compared with Pt/C.Noticeably,the preparation method of such a high-performance catalyst is simple and easy to optimize,suitable for the large-scale production.What’s more,it opens up a more sustainable development scenario to reduce the hazardous wastes such as LiFePO4 by directly using them for preparing high-performance ORR catalysts.