NRP۱ gene expression changes in gastric cancer patients treated with doxycycline

Introduction Gastric cancer (GC) ranks fifth for incidence and fourth for mortality with over ۱ million new cases and ۷۶۸,۰۰۰ deaths worldwide in ۲۰۲۰. Since GC is mostly asymptomatic until it progresses to advanced stages, the early detection using effective screening approaches is important to impair GC mortalities. Biomarkers are characteristics that are objectively measured and evaluated as an indicator of normal biologic process, pathogenic processes, or pharmacological response to a therapeutic intervention. Various biomarkers related to DNA, RNA, exosome, etc. have been found by recent advances in genome analysis. Development of these biomarkers in the field of cancer treatment is expected to greatly contribute to the progress of cancer, selection of appropriate therapeutic strategies and efficient follow-up programs. In this article, NRP۱ gene expression is studied as a diagnostic biomarker in GC patients treated with doxycycline compared to other patients. Methods Microarray analysis was performed on GSE۱۲۴۰۲۲ in the field of gastric cancer from the GEO database. NRP۱ gene was selected as a gene with significantly increased expression after checking in the GEPIA۲ database, and the survival analysis of this gene was also analyzed in this database. The signaling pathways that were effective in GC were investigated through the KEGG database. Gene Ontology analysis was performed on NRP۱ gene through Enricher database. After analyzing the SNPs related to the NRP۱ gene through SIFT, miRNASNP and dbSNP databases, one SNP was selected in the ۳'UTR region and one SNP was selected in the coding sequence, and its effects on the target gene were compared with the Hope database was analyzed. Protein-protein interaction of NRP۱ gene was analyzed by STRING database, which interacted with ۱۰ other genes. Results According to microarray analysis and box plot diagramming and survival analysis, NRP۱ gene was identified as a gene with increased expression in GC patients. This gene was effective in Axon guidance signaling pathway as a receptor. SNP rs۱۵۰۷۱۲۲۱۴ was effective in increasing the expression of NRP۱ gene by disconnecting ۷ miRNAs in the ۳'UTR region. The coding sequence SNP rs۱۹۹۶۷۳۵۳۹ was found to have a change at amino acid position ۳۷۰ from Isoleucine to Threonine after checking with the Hope database. And the result was that the mutant residue is smaller than the wild-type residue. The wild-type residue is more hydrophobic than the mutant residue. After gene ontology analysis, Endoderm Formation biological process had similarities between NRP۱ gene and GC and doxycycline. Conclusions After bioinformatic analyzes performed on gastric cancer patients treated with doxycycline, the NRP۱ gene was selected as a significantly increased expression gene that can be used as a diagnostic biomarker in gastric cancer patients treated with doxycycline. SNPs rs۱۵۰۷۱۲۲۱۴ and rs۱۹۹۶۷۳۵۳۹ can be effective in increasing NRP۱ gene expression.

کلیدواژه ها:

Gastric cancer ، Bioinformatics ، Genomics ، Biomarkers ، Microarray Research