Reconstructing pathway modification induced by nicotinamide using multi-omics network analyses in triple negative breast cancer

Triple negative breast cancer (TNBC) is characterized by an aggressive biologic behavior without specific targeted agent. Nicotinamide has recently been proved as a novel therapeutic agent for skin tumors in ONTRAC trial. Here we performed combinatory transcriptomic and in-depth proteomic analyses to characterize network of molecular interactions in TNBC cells treated by nicotinamide. Multi-omics with The Illumina sequencing (HiSeq™ 2500) for transcriptomics and iTRAQ LC-MS/MS techniques for proteomics profiles identified that nicotinamide causes significant functional alterations to major cellular pathways, including cell cycle, DNA replication, apoptosis and DNA damage repair. Pathway enrichment analyses were conducted using multiple web-based analytic tools to categorize functions of genes and peptides. This approach reveals that nicotinamide treatment rewires interaction networks towards dysfunction of DNA damage repair and away from pro-growth state in TNBC. We are expecting that our multi-omics findings will provide knowledge of integrational signaling networks alteration with NA treatment in TNBC and act as an evidence for application of NA as a novel chemotherapeutic agent in the future.