Perineural invasion on prostate cancer is associated with Schwann cells and circadian rhythm-related genes disruption: a bioinformatics approach

Abstract

Abstract Studies have shown that Schwann cells participate in the tumor microenvironment, producing several factors that benefit cancer cells. During this process, Schwann cells are dedifferentiated and help the process of cancer cellular proliferation. These cells then migrate to the region close to the tumor tissue and assist the development of the neoplastic cell. In this context, the present study aimed to evaluate the influence of Schwann cells on prostate cancers. We investigated the association between Schwann cells and prostate cancer often associated with perineural invasion. Initially, we used the GEO Datasets platform from the GEO repository to identify a database reporting gene expression in Schwann cells in a neoplastic context. Briefly, the database contains the expression results from experiments in which two factors produced by tumor cells were added to cell cultures. Comparisons were made between samples from the first and third passages. We then used these data to perform differential gene expression analysis and crossed data from upregulated genes with differential expression data from negative and positive perineural invasion prostate cancers. We observed that the “axon guidance” pathway was upregulated in negative perineural invasion prostate cancers. Meanwhile, upregulated mRNAs activate the “axon guidance” and, together with ROBO1 and MPZ upregulation, inhibit perineural invasion pathways. Both genes are also associated with Schwann cell migration inhibition. PER3, NR3C1, PPARGC1A, TIMP3, ID2, PDE6B, and CAVIN1 were upregulated in negative perineural tumors, while SLC25A10 was upregulated. We also observed upregulated genes in positive perineural invasion: PPARGC1A, TIMP3, S100A8, ID2, DEFB1, AQP3, ASS1, PDE6B, NEFH, and CAVIN1. AQP3 and NEFH were upregulated only in positive perineural invasion tumors and PER3 and NR3C1 were upregulated only in negative perineural invasion samples. We believe that Circadian rhythm and/or melatonin disruption could be associated with Schwann cells dedifferentiation; consequently, Schwann cells produce different factors that will participate in various processes of tumor progression. These processes may also be involved in tumor invasion into the perineural tissue in prostate cancer.