285P - Higher MCTS1 mRNA level in breast cancer may associate with an unfavorable outcome

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer, Metastatic
Breast Cancer
Translational Research
Presenter Yumei Shi
Citation Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365
Authors Y. Shi, N. Liao, G. Zhang, C. Ren, L. Wen, W. Zhu, X. Chen
  • Breast, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN

Abstract

Background

The oncogene MCTS1 was originally discovered as an amplified product in a subset of T-cell lymphoma lines. It has been involved in cell cycle progression and conferring a growth advantage in lymphomas. However, the role of MCTS1 in predicting the outcome of breast cancer patients remains unclear.

Methods

GEPIA was a newly–developed web server for gene expression profiling and interactive analyses. We analyzed the gene expression profile across the clinical and RNA-seq data of 1085 breast cancer and 291 normal breast tissue based on TCGA and GTEx data.

Results

The results showed that MCTS1 was one of the most differential survival genes, and the median expression levels of MCST1 in breast cancer and normal tissue were 51.3 and 32.7 respectively. The overall survival of breast cancer patients with high MCTS1 mRNA level was inferior to that with low MCTS1 mRNA level (Logrank p = 2.3e−06). Cox Proportional Hazards Model analysis showed that MCST1 mRNA level in tumor was an independent predictor for overall survival status in breast cancer patients (HR = 2.2, p(HR)=4.1e−06). We inquired MCST1 on UCSC Genome Browser on Human Dec. 2013 (GRCh38/hg38) Assembly, and the result showed that H3K27ac, an active enhancer mark associated with the activation of transcription, was highly modified in promoter subdomain. We further analyzed the functional protein association networks on the String database, which showed that DENR involved in the translation of target mRNAs by recognizing the initiation codon were related to breast cancer with high MCTS1 mRNA expression.

Conclusions

In conclusion, higher MCTS1 mRNA level in breast cancer may associate with an unfavorable outcome due to H3K27ac modified MCTS1 promoter hyperacylation, which promotes its expression to inhibit apoptosis and cell cycle progression. To further confirm it, the experiment about the transfection of the shRNA on target gene is undergoing.

Clinical trial identification

Legal entity responsible for the study

Guangdong Academy of Medical Sciences & Guangdong General Hospital, Guangzhou, China Guangdong Academy of Medical Sciences & Guangdong General Hospital, Guangzhou, China

Funding

None

Disclosure

All authors have declared no conflicts of interest.