Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Med Sci Monit. 2018 Mar 23;24:1701-1711. doi: 10.12659/msm.909128.
BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined. RESULTS The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.
多年来，化疗一直是晚期胃癌（GC）患者的主要治疗方法。尽管在化疗中加入抗血管生成药物可以略微提高患者的生存率，但对于肿瘤学家来说，确定抗血管生成治疗敏感的患者仍然具有挑战性。粒细胞集落刺激因子（G-CSF）可促进肿瘤生长和血管生成，而抗 G-CSF 抗体可最大程度地减少这种作用。因此，G-CSF 可能是一种潜在的肿瘤标志物。然而，G-CSF 和 G-CSFR 表达对 GC 患者生存的影响尚不清楚。
收集 70 例 GC 组织样本，通过免疫组织化学法检测 G-CSF 和 G-CSFR。使用 ELISA 法共检测 40 对 GC 组织及其配对的相邻黏膜组织中的 G-CSF 和 G-CSFR 水平。分析 G-CSF/G-CSFR 与临床特征、VEGF-A 水平和总生存期之间的相关性。使用 SGC7901 细胞系进行生物学功能和潜在机制研究，并检测 G-CSF 对肿瘤增殖、迁移和管形成的影响。
GC 组织中 G-CSFR 的水平高于正常黏膜组织。G-CSF 表达水平较高与肿瘤晚期、肿瘤 VEGF-A 和血清 CA724 水平较高有关，而 G-CSFR 表达水平较高与淋巴结转移有关。G-CSF 表达较高的患者总生存期较短。体外，G-CSF 通过 JAK2/STAT3 通路刺激 SGC7901 增殖和迁移，并加速 HUVEC 管形成。
这些数据表明，肿瘤中 G-CSF 和 G-CSFR 的增加通过刺激肿瘤增殖、迁移和血管生成，导致 GC 患者预后不良，表明这些因素是癌症治疗的潜在肿瘤靶点。
