Department of Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Department of Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Oncol Rep. 2018 Jun;39(6):2978-2986. doi: 10.3892/or.2018.6376. Epub 2018 Apr 18.
Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide, especially in East Asia. Discovery of new biomarker and the elucidation of the molecular mechanisms involved in GC development and progression continue to be important issues for both researchers and clinicians. In the present study, we report that siRNA knockdown of heat shock protein family B (small) member 8 (HSPB8) inhibited the proliferation of GC cells and promoted their apoptosis. Analysis of TCGA dataset indicated that the HSPB8 expression level was strongly positively correlated with the KEGG MAPK signaling pathway (P<0.001, FDR=0.006) and BIOCARTA CREB pathway (P=0.006, FDR=0.043). The association between HSPB8 and the ERK‑CREB pathway was confirmed by western blot analysis and we found that pERK and pCREB were significantly decreased following HSPB8 knockdown. Downstream genes of the ERK‑CREB pathway were all significantly decreased following HSPB8 knockdown. By evaluating the survival of TCGA GC patients, we found that patients with a high HSPB8 level exhibited significantly worse prognosis than those with low HSPB8 in both overall survival (OS) (log‑rank χ2=10.60, P=0.001) and disease‑free survival (DFS) (log‑rank χ2=11.31, P<0.001). The methylation level of HSPB8 DNA was significantly negatively associated with its expression (R=‑0.1368, P=0.041), and positively associated with OS (log‑rank χ2=10.60, P=0.001). In conclusion, we provide evidence that HSPB8 promotes cancer cell growth by activating the ERK‑CREB pathway and may serve as a potential prognostic factor in GC patients.
胃癌（GC）是世界上最常见的恶性肿瘤之一，尤其是在东亚。发现新的生物标志物和阐明参与 GC 发生和发展的分子机制，一直是研究人员和临床医生关注的重要问题。在本研究中，我们报告 HSPB8 的 siRNA 敲低抑制了 GC 细胞的增殖并促进了其凋亡。TCGA 数据集的分析表明，HSPB8 的表达水平与 KEGG MAPK 信号通路（P<0.001，FDR=0.006）和 BIOCARTA CREB 通路强烈正相关（P=0.006，FDR=0.043）。通过 Western blot 分析证实了 HSPB8 与 ERK-CREB 通路之间的关联，我们发现 HSPB8 敲低后 pERK 和 pCREB 显著降低。ERK-CREB 通路的下游基因在 HSPB8 敲低后均显著降低。通过评估 TCGA GC 患者的生存情况，我们发现 HSPB8 水平高的患者在总生存（OS）（对数秩 χ2=10.60，P=0.001）和无病生存（DFS）（对数秩 χ2=11.31，P<0.001）方面的预后明显比 HSPB8 水平低的患者差。HSPB8 DNA 的甲基化水平与其表达呈显著负相关（R=‑0.1368，P=0.041），与 OS 呈正相关（对数秩 χ2=10.60，P=0.001）。总之，我们提供的证据表明 HSPB8 通过激活 ERK-CREB 通路促进癌细胞生长，可能成为 GC 患者的潜在预后因素。
