Page 89 - GPD-3-3

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Perineural invasion in prostate cancer is

associated with Schwann cells and disruption
of circadian rhythm-related gene expression: A

bioinformatics approach

Sérgio Lopes Silva, Genilda Castro de Omena Neta, Rodger Marcel Lima Rocha,
Ana Kelly da Silva Fernandes Duarte, and Carlos Alberto de Carvalho Fraga*

Complex of Medical and Nursing Sciences, Federal University of Alagoas, Campus Arapiraca,
Arapiraca, Alagoas, Brazil

Abstract

Schwann cells in the tumor microenvironment are reportedly involved in the
production of several factors that benefit cancer cell growth. During this process,
Schwann cells are dedifferentiated and facilitate cancer cellular proliferation.
The cells then migrate to the region close to the tumor tissue and assist the
development of the neoplastic cells. Accordingly, the present study was designed
to evaluate the perineural invasion in prostate cancer, in association with disrupted
circadian rhythm-related gene expression in Schwann cells. Initially, we identified
a database reporting gene expression in Schwann cells in a neoplastic context
*Corresponding author:
Carlos Alberto de Carvalho Fraga from the GEO Datasets platform in the GEO repository. The database contains the
(carlos.fraga@arapiraca.ufal.br) expression results from experiments in which two factors produced by tumor cells
Citation: Silva SL, de Omena were added to cell cultures. Comparisons were made between samples from the
Neta GC, Rocha RML, da Silva first and third passages. Then, these data were used in differential gene expression
Fernandes Duarte AK, de Carvalho analysis and combined with differential expression data of genes upregulated in
Fraga CA. Perineural invasion
in prostate cancer is associated perineural invasion-negative and -positive prostate cancers. We observed that
with Schwann cells and disruption the “axon guidance” pathway was upregulated in perineural invasion-negative
of circadian rhythm-related gene prostate cancers. Meanwhile, upregulated mRNAs activated the “axon guidance”
expression: A bioinformatics
approach. Gene Protein Dis. pathway and, together with ROBO1 and MPZ upregulation, inhibited perineural
2024;3(3):3146. invasion pathways. Both genes are also associated with inhibition of Schwann cell
doi: 10.36922/gpd.3146 migration. PER3, NR3C1, PPARGC1A, TIMP3, ID2, PDE6B, and CAVIN1 were upregulated
Received: March 12, 2024 in perineural invasion-negative tumors, while SLC25A10 was upregulated. We also
Accepted: April 22, 2024 observed upregulated expression in perineural invasion-positive tumors for genes
Published Online: July 9, 2024
such as PPARGC1A, TIMP3, S100A8, ID2, DEFB1, AQP3, ASS1, PDE6B, NEFH, and CAVIN1.
Copyright: © 2024 Author(s). AQP3 and NEFH were upregulated only in perineural invasion-positive tumors and
This is an Open-Access article PER3 and NR3C1 were upregulated only in perineural invasion-negative samples. The
distributed under the terms of the
Creative Commons Attribution findings revealed that circadian rhythm and/or melatonin disruption are associated
License, permitting distribution, with dedifferentiation of Schwann cells, which consequently produce a set of factors
and reproduction in any medium, that drive tumor progression. These processes may also be involved in tumor invasion
provided the original work is
properly cited. into the perineural tissue in prostate cancer.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Bioinformatics; Prostate adenocarcinoma; Clock-related genes; Schwann cell
regard to jurisdictional claims in
published maps and institutional dedifferentiation
affiliations.

Volume 3 Issue 3 (2024) 1 doi: 10.36922/gpd.3146