Title

Prognostic significance of autophagy related genes in estrogen receptor positive tamoxifen treated breast cancer

Authors

Alok Mishra¹, Ankit Pateriya¹, Anand Kumar Mishra², Ashutosh Shrivastava^1*

Affiliation

¹Center for Advance Research, Faculty of Medicine, King George’s Medical University, Lucknow, Uttar Pradesh, India, 226003; ²Department of Endocrine Surgery, Faculty of Medicine, King George’s Medical University, Lucknow, Uttar Pradesh, India, 226003

Email

*Address correspondence to Ashutosh Shrivastava, ashutoshshrivastava@kgmcindia.edu

Article Type

Research Article

Date

Submitted on August 15, 2020; Revision August 11, 2020; Accepted August 11, 2020; Published September 30, 2020

Resistance to Tamoxifen constitutes a major therapeutic challenge in treating hormone sensitive breast cancer. The induction of autophagy has been shown to be involved as one of the mechanism responsible for Tamoxifen resistance. Autophagy related gene (ATG) members are the regulators and effectors of Macroautophagy process in the cellular systems. In this study, we evaluated the prognostic significance of ATGs in Tamoxifen treated breast cancer. The “Kaplan- Meier plotter” database was utilized to analyze the relevance and significance of ATGs mRNA expression to Relapse Free Survival in breast cancer patients. We used the data of patients who are Estrogen receptor positive and are treated with Tamoxifen. Hazard ratio and log-rank p-value were calculated using KM survival plots for various ATGs. Overexpressed ATG3, ATG 5, ATG 8B and PIK3R4 resulted in a poor prognosis. A gene signature of these ATGs predicts deteriorated RFS (p-value=8.3e-05 and HR=1.84 (1.35-2.51) and Distant Metastasis Free Survival (p value 0.0027 and HR=2.03 (1.27-3.26). We report the distinct prognostic values of ATGs in patients of breast cancer treated with Tamoxifen. Thus, better understandings of the induction of autophagy pathway may potentially form the basis for use of autophagy inhibitors in the Tamoxifen resistant breast cancer.

Keywords

Breast Cancer, Estrogen Receptor, Tamoxifen resistance, Autophagy, Autophagy related genes, Kaplan-Meier Plot

Citation

Mishra et al. Bioinformation 16(9): 710-718 (2020)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.