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Gene & Protein in Disease Perineural invasion in prostate cancer

1. Introduction benefit cancer cells. 16,17 During this process, Schwann
cells are dedifferentiated and facilitate the proliferation
Carcinogenesis is a complex process involving multiple of cancer cells⁠. 10,18,19 These cells then migrate to the region
genetic and epigenetic events that alter the normal close to the tumor tissue and drive the development of
functions of oncogenes and tumor suppressor genes⁠, the neoplastic cell⁠. Accordingly, the present study was
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resulting in an increased production of growth factors or designed to evaluate the perineural invasion in prostate
transcription factors, or an elevated expression of cell- cancers, in association with disrupted circadian rhythm-
surface receptors and intracellular signals⁠. The loss of
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tumor suppressor activity leads to a cellular phenotype related gene expression in Schwann cells.
capable of increasing cell proliferation and loss of cell 2. Methods
adhesion, enabling mutated cells to infiltrate local tissues
and spread to distant sites. Metastasis is the cause of 90% 2.1. Gene list collection
of cancer-related deaths and results in a diverse set of Gene lists were acquired from NCBI (www.ncbi.nlm.nih.
clinical manifestations⁠. Metastases occur when malignant gov/gene/) and GeneCards (https://www.genecards.org/)
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neoplastic cells leave the primary site and travel via by searching using Entrez IDs for perineural invasion-
blood and lymph vessels to new sites in the body where related genes. The gene lists and differentially expressed
they disseminate new colonies. Cancer cells then employ genes (DEGs) were combined and identified with Venn
various strategies to aid adaptation and subsequent Diagram 2.1.0 (http://bioinfogp.cnb.csic.es/tools/venny/
expansion and progression at new sites. Formation and index.html). 15,20
progression of cancer is a multisystemic process, involving
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the immune system, vascularization, and dissemination⁠. 2.2. RNA-seq and clinical information data from The
Metastasis is characterized by tumor growth, invasion of Cancer Genome Atlas (TCGA)
the basement membrane into submucosal tissues, vascular Genomic and clinical data of both normal and solid
and lymphatic formation, perineural and systemic tissue tumor tissues for two different types of cancer were
invasion, and subsequent progression⁠. 5,6 downloaded from TCGA using TCGAbiolinks (an
The extracellular matrix (ECM) plays a critical role R/Bioconductor software; http://bioconductor.org/
in tumor microenvironment. During tumor formation, packages/release/bioc/html/TCGAbiolinks.html) and the
neoplastic cells bind to molecules present in the ECM, interphase TCGAbiolinksGUI. For this analysis, “prostate
which facilitates communication with other cells, such as adenocarcinoma (PRAD)” was set as the selected cancer
neutrophils, fibroblasts, macrophages, lymphocytes, and type. We retrieved level data for raw count mRNA and
peripheral nervous system cells⁠. The ECM is especially miRNA expression (Illumina HiSeq 2000). Coexpression
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important in tumor formation and invasion as cells respond of upregulated and downregulated DEGs was identified
and adapt to the local microenvironment. This involves from the gene expression profiles using Venn Diagram
both the unregulated proliferation of tumor cells and 2.1.0 (http://bioinfogp.cnb.csic.es/tools/venny/index.
the modification of the immediate environment in favor html). An adjusted p < 0.05 and a logFC ≥ 1 were set as the
of cell survival, angiogenesis, and tumor growth. Factors cutoff criteria. 21,22
that can degrade the ECM also facilitate tumor formation
and invasion. For example, matrix metalloproteinases 2.3. Inclusion criteria for studies
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(MMPs) have been associated with the degradation of The GEO database (https://www.ncbi.nlm.nih.gov/geo/)
basement membranes and ECM, facilitating the invasion was searched to identify publicly available gene expression
and metastasis of tumor cells, as well as promoting cell profiling studies associating Schwann cells and cancer.
proliferation, metastasis, and angiogenesis. 8,11,12 In addition After reviewing the studies, only one gene expression
to the degradation of the matrix, another important aspect profile (GSE4030) was downloaded from the GEO
in the formation and invasion of the tumor is a process database. GEO2R was applied to compare gene expression
called epithelial–mesenchymal transition, which allows profiles in passage 1 and passage 3 human Schwann cells
the tumors’ epithelial cells to produce factors generally exposed to growth factors, (heregulin and forskolin). Since
found in the ECM. 13 both cell groups had been exposed to mitogens, their
Studies have shown that circadian entrainment differences in gene expression profiles were interpreted as
disruption is associated with dedifferentiation of Schwann changes caused by prolonged versus short-term exposure
cells. 14,15 We suppose that clock genes are involved in the to mitogens. GEO2R (http://www.ncbi.nlm.nih.gov/geo/
deregulation of tumor microenvironment and Schwann geo2r/) is an interactive web tool for comparing two groups
cells, impacting the production of several factors that of GEO series data. The adjusted p values using Benjamini

Volume 3 Issue 3 (2024) 2 doi: 10.36922/gpd.3146