Identification of predictors based on drug targets highlights accurate treatment of goserelin in breast and prostate cancer

Yue Zhao,Huimin Sun,Jianzhong Zheng,Chen Shao,Dongwei Zhang

doi:10.1186/s13578-020-00517-w

Abstract

Goserelin is an effective alternative to surgery or estrogen therapy in prostate cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. However, not all users of goserelin can benefit from it, or some patients are not sensitive to goserelin. The advent of network pharmacology has highlighted the need for accurate treatment and predictive biomarkers. In this study, we successfully to identify 76 potential targets related to the compound of goserelin through network pharmacology approach. We also identified 18 DEGs in breast cancer tissues and 5 DEGs in cells, and 6 DEGs in prostate cancer tissues and 9 DEGs in cells. CRABP2 is the common DEG both in breast and prostate cancer. The risk prediction models constructed with potential prognostic targets of goserelin can successfully predict the prognosis in breast and prostate cancer, especially for very young breast cancer patients. Moreover, seven subgroups in breast cancer and six subgroups in prostate cancer were respectively identified based on consensus clustering using potential prognostic targets of goserelin that significantly influenced survival. The expression of representative genes including CORO1A and ANXA5 in breast and DPP4 in prostate showed strong correlations with clinic-pathological factors. Taken together, the novel signature can facilitate identification of new biomarkers which sensitive to goserelin, increase the using accuracy of goserelin and clarify the classification of disease molecular subtypes in breast and prostate cancer.

Highlights

Goserelin is a synthetic analogue of gonadotrophinreleasing hormone (GnRH) which stimulates gonadotrophin and sex hormone release in the short term, and causes suppression with continued administration [1, 2]
The relationship between compound and target genes were shown in red lines, and the protein protein interaction (PPI) relationship of the target genes were shown in blue lines
To explore the biological functions of 76 target genes, they were categorized into biological process (BP), cellular component (CC), and molecular function (MF)

Summary

Introduction

Goserelin is a synthetic analogue of gonadotrophinreleasing hormone (GnRH) which stimulates gonadotrophin and sex hormone release in the short term, and causes suppression with continued administration [1, 2]. Breast and prostate cancer are the most commonly diagnosed nonskin cancer in women and men, respectively [3]. About 30% to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy [5]. Goserelin is an effective alternative to surgery or estrogen therapy in prostate cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Network pharmacology (NP) was proposed as a promising approach to discover drugs from a systems perspective and at the molecular level. It combines bioavailability prediction, multiple drug target prediction and network analysis to understand the active compounds and therapeutic targets of drug [6, 7].

Methods

Results

Discussion

Conclusion