555P - Systems-wide bioinformatics analysis using next generation transcriptome and proteomics reveals nicotinamide transforms molecular signaling network...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Translational Research
Presenter HanSuk Ryu
Citation Annals of Oncology (2016) 27 (suppl_9): ix179-ix180. 10.1093/annonc/mdw601
Authors H. Ryu1, D. Han2, J.Y. Kim1, H. Lee3
  • 1Pathology, Seoul National University Hospital (SNUH)-Yongon Campus, 110-744 - Seoul/KR
  • 2Biomedical Research Institute, Seoul National University Hospital (SNUH)-Yongon Campus, 03082 - Seoul/KR
  • 3Radiation Oncology, Kangbuk Samsung Hospital, 03181 - seoul/KR

Abstract

Background

The Phase III ONTRAC trial has presented optimistic results that oral nicotinamide (NA) had protective effects in skin cancer, which is now being expected as a novel therapeutic agent. Triple negative breast cancer (TNBC) is characterized by an aggressive biologic behavior without specific targeted agent. Recently clinical trials have undergone to find supplementary agents such as Olaparib, boosting cytotoxic effects of current standard chemotherapeutic regimen, which is expected to go for NA. So far, however, no studies have presented a signaling alterations with NA treatment using next generation multi-omics methods based on bioinformatics analysis to understand intricate intracytoplasmic molecular pathways.

Methods

The Illumina sequencing (Hiseq 2500) and iTRAQ LC-MS/MS techniques were employed for transcriptomic and proteomic analyses, respectively, of TNBC cells treated with and without 25mM NA. Pathway enrichment analyses were conducted using web-based analytic tools to categorize their function of genes and peptides according to molecular pathway. Finally, networking analytic tools were adopted to visualize integration signaling interactions. Western blot, immunofluorescence and MTT assay for supplementary analyses were conducted to validate outcomes of multi-omics data.

Results

By enrichment analysis of the muti-omics, seven pathways showed significant differential expression of genes between the two groups. Gene set enrichment and pathway network interactions analysis provide sophisticated molecular signaling network rewiring toward suppression of cell cycle progression, loss of function of DNA damage repair and upregulation of pro-apoptotic condition after treatment of NA which all eventually provokes tumor cell death in TNBC cells.

Conclusions

This study highlights the landscape of mRNA and protein alterations after NA treatment in TNBC. We are expecting our multi-omics findings can provide knowledge of integrational signaling networks alteration with NA treatment in TNBC and an evidence for application of NA as a novel chemotherapeutic agent in the future.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.