GLIS2 redundancy causes chemoresistance and poor prognosis of gastric cancer based on co-expression network analysis

Gastric cancer is currently the fourth most common cancer and the third leading cause of cancer-associated mortality worldwide. Studies have identified that certain biomarkers contribute to the prognosis, diagnosis and treatment of gastric cancer. However, the biomarkers of gastric cancer are rarely used clinically. Therefore, it is imperative to define novel molecular networks and key genes to guide the further study and clinical treatment of gastric cancer. In the present study, raw RNA sequencing data and clinicopathological information on patients with gastric cancer were downloaded from The Cancer Genome Atlas, and a weighted gene co-expression network analysis was conducted. Additionally, functional enrichment and protein-protein interaction analyses were implemented to further examine the significant modules. As a result, 16 modules of highly correlated genes were acquired and colour coded, and the yellow module containing 174 genes associated with chemotherapy resistance and prognosis in gastric cancer was further analysed. The biological processes of the yellow module were primarily associated with cell adhesion, vasculature development and the regulation of cell proliferation. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways primarily involved the transforming growth factor-β signalling pathway, the cellular tumour antigen p53 signalling pathway, extracellular matrix-receptor interactions and focal adhesions. Notably, survival analysis and cell verification confirmed that high expression of GLIS family zinc finger 2 is significantly associated with chemoresistance and a worse prognosis in gastric cancer, and that this high expression is likely to be an important biomarker for the guidance of clinical treatment and prognostic evaluation.