The role of luteinizing hormone and its associated genes in progression of breast cancer: a bioinformatics approach
-
Afsaneh Tavasoli,1 Sima Kalantari,2,*
1. Department of Biotechnology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran.
2. Regenerative Medicine group (REMED), Universal Scientific Education & Research Network (USERN), Tehran, Iran.
- Introduction: Breast cancer is a major public health problem for women, and in many cases distant metastases and recurrence are the leading cause of death among patients. About 80% of diagnosed breast cancers are hormone-dependent, commonly hormones secreted by the hypothalamic-pituitary-gonadal (HPG) axis. These hormones, as well as regulating the reproductive system functions, can stimulate tumor development and progression in the tissues that have receptors for these hormones. The direct correlation of circulating levels of gonadotrophins (LH, FSH, and HCG) with tumor progression in an invivo model of breast cancer has been reported. In addition other investigations have shown that luteinizing hormone (LH) modulates the expression of a set of genes associated with tumorigenesis in breast cancer cell lines. The aim of the present study was elucidate the role of the LH associated genes on breast cancer metastasis using bioinformatics approach.
- Methods: STITCH database was utilized to find direct protein targets (DPT) of LH receptor and CTD database was used to identify DPT-associated genes. Then STRING database was employed to construct an interaction network of DPTs and DPT-associated genes. Resulted network was analyzed Using Cytoscape v3.7.0. to identify the most potentially effective genes (hubs and bottlenecks). Also, MCODE algorithm was used to screen the modules and sub-networks. Finally, the expression levels of identified genes were subsequently investigated from early stage to metastasis (stage: I – IV) in breast tumor tissues based on TCGA data reported in UALCAN.
- Results: Nine DPT and 1456 DPT-associated genes were identified for LH receptor. Their network analysis based on degree and betweenness parameters identified overall 22 hubs and bottlenecks as the most potentially effective genes. MCODE analysis identified 30 clusters from the network that among them cluster 1 with the highest score was containing 49 nodes and 1111 edges in which UBB, UBC, UBA52, EEF2, EEF1A1, and RPS27A were identified as common genes between nodes of cluster 1 and hub and bottleneck genes. TCGA data showed significant decreasing trend in expression levels of EEF2, EEF1A1, and RPS27A genes from stage I to IV in breast tumor tissue. While, increment of UBB expression level and not significant changes for UBC and UBA52 expression levels were observed during breast tumor progression from stage I to IV.
- Conclusion: We identified a four-gene set (UBB, EEF2, EEF1A1, and RPS27A) associated with LH receptor that expressed in breast tumor. Down-regulation of EEF2, EEF1A1, and RPS27A from stage I to IV can suggest their tumor inhibitor role in breast tissue whereas up-regulation of UBB may offer its role as a tumor activator during breast tumor progression from early stage to metastasis. But, for verification of these bioinformatics results experimental study is needed.
- Keywords: breast cancer, luteinizing hormone, tumor progression, bioinformatics
