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Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer

Tao Yu, Wenzhuo Jia, Qi An, Xianglong Cao, Gang Xiao

(Department of General Surgery, Beijing Hospital, National Center of Gerontology, Beijing, China (mainland))

Med Sci Monit 2018; 24:1847-1855

DOI: 10.12659/MSM.906176

BACKGROUND: This study assessed the prognostic value of GLI1 in gastric cancer and analyzed the possible GLI1-related signaling network in chemosensitivity.
MATERIAL AND METHODS: Bioinformatic data mining was performed by using data in the TCGA-Stomach Cancer (TCGA-STAD) and the Kaplan-Meier plotter. GLI1 co-expressed genes in TCGA-STAD were subjected to KEGG pathway analysis. The genes enriched in the KEGG pathways were further subjected to Protein-Protein Interaction (PPI) analysis.
RESULTS: In TCGA-STAD, high GLI1 gene/exon expression was associated with significantly worse survival (p=0.016 and 0.0023 respectively). In the Kaplan-Meier plotter, high GLI1 expression was associated with unfavorable overall survival (OS) (HR: 1.68, 95%CI: 1.42–2, p<0.0001) and first progression-free survival (FPS) (HR: 1.72, 95%CI: 1.4–2.11, p<0.0001). In TCGA-STAD, 600 GLI1 co-expressed genes were identified (absolute Pearson’s r ≥0.5). The most significant pathways were pathways in cancer (p=230.0E-12) and the Hedgehog signaling pathway (p=6.9E-9). PI3K-AKT pathway (p=17.0E-9) has the largest proportion of gene enrichment. Some GLI1 co-expressed genes in the PI3K-AKT pathway are central nodes in the PPI network and also play important roles in chemosensitivity of gastric cancer. Nevertheless, the mechanisms underlying their co-expression are still largely unexplored.
CONCLUSIONS: High GLI1 expression is associated with unfavorable OS and FPS in patients with gastric cancer. As a member of the Hedgehog signaling pathway, GLI1 co-expressed genes are also largely enriched in PI3K/AKT pathway in gastric cancer, which is closely related to chemoresistance. The underlying mechanisms are still largely unexplored and need further study.

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