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Gene & Protein in Disease Perineural invasion in prostate cancer

and Hochberg false discovery rate method by default were term depression, glutamatergic synapse and leukocyte
applied to correct the occurrence of false-positive results. transendothelial migration were pathways upregulated
An adjusted p < 0.05 and a logFC ≥ 1 were set as the cutoff only in perineural invasion-negative tumors. Chemical
criteria. 23 carcinogenesis, calcium signaling pathway, oxytocin
The Kyoto Encyclopedia of Genes and Genomes signaling pathway, transforming growth factor beta
(KEGG) is an integrated database resource for biological (TGFβ) signaling pathway, tryptophan metabolism,
interpretation of genome sequences and other high- amebiasis and cardiac muscle contraction migration were
throughput data. KEGG analyses are available at the upregulated only in perineural invasion-positive tumors
DAVID database (https://david.ncifcrf.gov/), a data (Supplementary File 1 Tables S1-S4).
resource composed of an integrated biology knowledge The gene expression profiles of both early- and late-
base and analytic tools to extract meaningful biological passage human Schwann cells exposed to heregulin
information from large quantities of genes and protein and forskolin, contained in a GEO dataset, were used to
collections. A p < 0.05 was set as the cutoff criterion. 24 identify DEGs with the aid of GEO2R. This online tool was
applied to compare gene expression profiles in passage 1
2.4. Prostate cancer expression analyses and passage 3 human Schwann cells exposed to heregulin
Several other web resources were also used to obtain and forskolin. Since both cell groups had been exposed
information for prostate cancer expression studies, to mitogens, differences in gene expression profiles
while some others were used as analytic tools. were interpreted as changes caused by prolonged versus
Immunohistochemistry image-based protein data for short-term exposure to mitogens. From this analysis, we
both normal and cancer samples are available at the identified a set of upregulated DEGs, which modulate
Human Protein Atlas (https://www.proteinatlas.org/). pathways such as neuroactive ligand-receptor interaction,
Outputs of DNA methylation analyses were obtained from maturity-onset diabetes of the young, and tyrosine
MEXPRESS dataset (https://mexpress.be/?ref=labworm). metabolism. Meanwhile, pathways that were enriched for
The DNA methylation data in the cancer dataset (Illumina downregulated DEGs in cancer include focal adhesion,
Infinium Human Methylation 450 K Bead array, Illumina, arrhythmogenic right ventricular cardiomyopathy,
USA) were classified as significant hypermethylation only adherens junction, basal cell carcinoma, p53 signaling
if the β value exceeded 5% of the tumors. Copy number pathway, colorectal cancer, progesterone-mediated oocyte
alteration analysis was performed using the cBio Cancer maturation, oocyte meiosis, Hedgehog signaling pathway,
Genomics Portal (http://cbioportal.org). Survival analysis ECM-receptor interaction, melanogenesis, calcium
of the TCGA data was performed using the survival signaling pathway, dilated cardiomyopathy, cell cycle, and
module of the Tumor Immune Estimation Resource amyotrophic lateral sclerosis.
(TIMER). Additionally, Kaplan–Meier plots were drawn
using TIMER to explore the association between clinical 3.2. Overview of the cancer transcriptomic analysis
outcome and gene expression, and to visualize survival We employed a systematic and integrative approach to
differences. 25 analyze cancer type-specific and Schwann cell-specific
DEGs, with the aim to construct a cancer network. We first
3. Results determined DEGs by comparing gene expression levels
3.1. Identification of differentially expressed between tumor and normal samples. A Venn diagram was
genes, gene ontology enrichment, and functional then constructed to visualize the overlap between DEG
classification genes, both upregulated and downregulated, from both
We obtained gene expression data belonging to prostate cancer and Schwann cells. Among the upregulated genes
adenocarcinoma specimens from TCGA; these data were from perineural invasion-negative and -positive samples,
preprocessed using standard methods. We performed we identified 166 and 142 DEGs, respectively, that were
a DEG analysis using data obtained from patients with coexpressed in Schwann cells.
perineural invasion-positive and -negative prostate We also performed a KEGG analysis to investigate
adenocarcinoma. According to DAVID analysis, cell pathways with major expression changes in Schwann
adhesion molecules (CAMs), pathways in cancer, cell lines and perineural invasion-negative or -positive
melanogenesis, gap junction, Circadian entrainment, Fc tumors, based on previously identified upregulated
gamma R-mediated phagocytosis, gastric acid secretion, DEGs. The analysis revealed that microRNAs in cancer,
axon guidance, histidine metabolism, viral myocarditis, complement and coagulation cascades, Hippo signaling
serotonergic synapse, small cell lung cancer, long- pathway and transcriptional misregulation in cancer were

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