Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

Elena A Pudova,George S Krasnov,Marina V Kiseleva,Nataliya V Melnikova,Anastasiya A Belova,Andrey D Kaprin,Anna V Kudryavtseva,Nadezhda N Volchenko,Gennady D Efremov,Anastasiya V Snezhkina,Boris Y Alekseev,Andrew R Zaretsky,Kseniya M Klimina,Maria V Savvateeva,Anastasiya A Kobelyatskaya,Kirill M Nyushko,Dmitry S Mikhaylenko,Elena N Lukyanova

doi:10.3389/fgene.2019.00730

Abstract

Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug therapy efficacy, as well as possible therapeutic targets. We have performed a bioinformatic analysis of a The Cancer Genome Atlas (TCGA) data and RNA-Seq profiling of a Russian patient cohort to reveal prognostic markers of locally advanced lymph node-negative prostate cancer (lymph node-negative LAPC). We also aimed to identify markers of the most common molecular subtype of prostate cancer carrying a fusion transcript TMPRSS2-ERG. We have found several genes that were differently expressed between the favorable and unfavorable prognosis groups and involved in the enriched KEGG pathways based on the TCGA (B4GALNT4, PTK6, and CHAT) and Russian patient cohort data (AKR1C1 and AKR1C3). Additionally, we revealed such genes for the TMPRSS2-ERG prostate cancer molecular subtype (B4GALNT4, ASRGL1, MYBPC1, RGS11, SLC6A14, GALNT13, and ST6GALNAC1). Obtained results contribute to a better understanding of the molecular mechanisms behind prostate cancer progression and could be used for further development of the LAPC prognosis marker panel.

Highlights

Aging is a complex phenomenon, which is characterized by the deregulation of various cellular processes and involves metabolic, epigenomic, transcriptomic, genomic, and proteomic alterations, and leads to death
KEGG pathway enrichment analysis was carried out using all set of identified differentially expressed genes (DEGs) (173 genes)
An age-dependent disease, is caused by alterations in various molecular genetic mechanisms, including mutations and epigenetic changes followed by perturbations in cell signaling and metabolic pathways

Summary

Introduction

Aging is a complex phenomenon, which is characterized by the deregulation of various cellular processes and involves metabolic, epigenomic, transcriptomic, genomic, and proteomic alterations, and leads to death. Prognostic Markers in Prostate Cancer accumulate throughout the life of a cell. These alterations can initiate activation of oncogenes and deactivation of tumor suppressor genes resulting in tumorigenesis. One of the main causes of cancers is the disruption of cellular senescence, which is associated with proliferative arrest blocking multiplication of potentially malignant cells. PC is associated with aging through the disruption of glandular homeostasis, which is caused by an imbalance between cell proliferation and death. The imbalance between mitosis and apoptosis leads to various diseases, including prostate cancer (Plati et al, 2011)

Objectives

Methods

Results

Conclusion