Features of cancer-testicular antigen genes transcriptional activity regulation in gastric cancer

Introduction. Gastric cancer remains a serious public health problem. Cancer-testicular antigen genes (CT-genes) in gastric cancer may be promising targets for immunotherapy due to their limited expression in normal tissues. Competing endogenous RNA networks (ceRNAs) play an important role in regulating CT-gene expression in gastric cancer. These networks are complex and require comprehensive bioinformatics and experimental study.
Aim. To conduct a bioinformatic analysis followed by validation of СT-gene expression and its regulation in malignant gastric tumors.
Materials and methods. Data for the bioinformatics stage were downloaded from GEO. Identification of differentially expressed genes was carried out using GEO2R, microRNA targeting genes – using the Random forest machine learning method. An analysis of the interaction of microRNA and long non-coding RNA (lncRNAs) was also performed. The clinical material for the experimental stage was tissues (tumor and conditionally normal) of 100 patients with a histologically confirmed diagnosis of gastric cancer. The relative expression values of 6 CT-genes (MAGEA10, MAGEA2, MAGEA12, MAGEA3, MAGEA6, MAGEH1), as well as their targeting microRNAs and lncRNAs, were determined using real-time polymerase chain reaction.
Results. Using GEO2R, 18,617 differentially expressed loci were detected, including protein-coding genes, microRNA and lncRNAs. Of these, a change in the expression of 6 CT-genes was revealed – MAGEA10, MAGEA2, MAGEA12, MAGEA3, MAGEA6, MAGEH1, interacting with 40 microRNAs, in turn interacting with 17 lncRNAs. In the patients tumor tissue, an increase in expression of the MAGEA10, MAGEA3 and MAGEA6 genes (p <0.0001), a decrease in expression of miR-1207-5p, -6858-5p, -3127-3p, -3940-3p, -6807-3p, -3085-3p, -3934-5p, -4488, -4530, -6777-3p, -99a-3p (p <0.0001) and an increase in expression of miR-7113-3p, miR-874-3p, as well as an increase in expression of LINC01089, AC145285.6, GAS5, AC005034.3, AL691447.2 (p <0.001) and decreased expression of SNHG14, AC002101.1, SLC9A3-AS1 and AL118506.1 (p <0.001) was found. Based on the obtained data, a model of the regulatory network for CT-genes in gastric cancer was constructed.
Conclusion. The study showed disturbances in the CT-genes competitively interacting RNA network in gastric adenocarcinoma. The obtained data are important for understanding the fundamental mechanisms of CT-gene regulation, as well as for improving approaches to immunotherapy (new targets and regulatory molecules) and diagnostics (new molecular markers) of this disease. 

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