In silico investigation of heparanase-correlated genes in breast cancer subtypes.

Carina Mucciolo Melo,Henrique Pereira Prado,Gabriela Araújo Attie,Manoel João Batista Castello Girão,Maria Aparecida Da Silva Pinhal,Daniel Lacaz Ruiz

doi:10.31744/einstein_journal/2020ao5447

Abstract

ABSTRACTObjective To investigate the possible genes that may be related to the mechanisms that modulate heparanase-1.Methods The analysis was conducted at Universidade Federal de São Paulo, on the data provided by: The Cancer Genome Atlas, University of California Santa Cruz Genome Browser, Kyoto Encyclopedia of Genes and Genomes Pathway Database, Database for Annotation, Visualization and Integrated Discovery Bioinformatics Database and the softwares cBioPortal and Ingenuity Pathway Analysis.Results Using messenger RNA expression pattern of different molecular subtypes of breast cancer, we proposed that heparinase-1 was co-related with its progression. In addition, genes that were analyzed presented co-expression with heparanase-1. The results that showed that heparanase-1 co-expressed with phosphoinositide 3-kinase adapter protein 1, sialic acid-binding immunoglobulin-like lectin 7, and leukocyte-associated immunoglobulin-like receptor 1 are directed related with immune system evasion during breast cancer progression. Furthermore, cathepsin L was co-expressed with heparanase-1 and transformed inactive heparanase-1 form into active heparanase-1, triggering extracellular matrix remodeling, which contributes to enhanced tumor-host interaction of the tumor.Conclusion The signaling pathway analysis using bioinformatics tools gives supporting evidence of possible mechanisms related to breast cancer development. Evasion genes of the immune system co-expressed with heparanase-1, a enzyme related with tumor progression.

Highlights

The publication of the first draft of the human genome in 2001 marked the beginning of a new era in biology: the age of bioinformatics
We propose to conduct this study on both isoforms of heparanase, namely heparanase-1 (HPSE) and heparanase-2 (HPSE2), in the context of breast cancer
We accessed www.cbioportal.org and downloaded data pertaining to invasive breast carcinoma (TCGA, Nature 2012).(5,6) The collected data refer to the expression of messenger RNA for HPSE and HPSE2 in different subtypes of breast cancer, such as luminal A/B (n=321), triple-negative/basal (n=81), and human epidermal growth factor receptortype 2 (HER2) (n=58) (Figure 1)

Summary

Introduction

The publication of the first draft of the human genome in 2001 marked the beginning of a new era in biology: the age of bioinformatics. Given the sheer amount of information being digitalized, genomics data can only be clearly understood with the help of data science and bioinformatics tools, such as pathway analysis software. One of the objectives of this study is to provide guiding documentation to healthcare professionals on how to answer biological questions relating to specific gene expression, and its correlation with other signaling pathways. Recent studies showed the correlation of HPSE with exosome formation, activation of the immune system, autophagy, and chemoresistance, demonstrating its importance in modulation of the crosstalk between tumor cells and the tumor environment. As a result of this finding, HPSE is a target for development of new drugs for cancer, and anti-HPSE treatment can be used to stimulate T cells and initiate anti-cancer immune responses.[2,3]

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Discussion

Conclusion