Department of General Surgery, Beijing Hospital, National Center of Gerontology, Beijing, China (mainland).
Med Sci Monit. 2018 Mar 29;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.
本研究评估了 GLI1 在胃癌中的预后价值，并分析了其在化疗敏感性中的可能相关信号网络。
通过使用 TCGA-胃癌（TCGA-STAD）和 Kaplan-Meier 绘图仪中的数据进行生物信息学数据挖掘。对 TCGA-STAD 中的 GLI1 共表达基因进行 KEGG 通路分析。KEGG 通路中富集的基因进一步进行蛋白质-蛋白质相互作用（PPI）分析。
在 TCGA-STAD 中，高 GLI1 基因/外显子表达与生存率显著降低相关（p=0.016 和 0.0023）。在 Kaplan-Meier 绘图仪中，高 GLI1 表达与不利的总生存期（OS）（HR：1.68，95%CI：1.42-2，p<0.0001）和首次无进展生存期（FPS）（HR：1.72，95%CI：1.4-2.11，p<0.0001）相关。在 TCGA-STAD 中，鉴定出 600 个 GLI1 共表达基因（绝对 Pearson's r ≥0.5）。最显著的通路是癌症通路（p=230.0E-12）和 Hedgehog 信号通路（p=6.9E-9）。PI3K-AKT 通路（p=17.0E-9）具有最大比例的基因富集。PI3K-AKT 通路中的一些 GLI1 共表达基因是 PPI 网络中的核心节点，在胃癌的化疗敏感性中也起着重要作用。然而，其共表达的机制在很大程度上仍未得到探索。
高 GLI1 表达与胃癌患者的不良 OS 和 FPS 相关。作为 Hedgehog 信号通路的成员，GLI1 共表达基因在胃癌中也大量富集在 PI3K/AKT 通路中，这与化疗耐药性密切相关。其潜在机制在很大程度上仍未得到探索，需要进一步研究。
