Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
J Cancer. 2015 Feb 15;6(4):342-50. doi: 10.7150/jca.10969. eCollection 2015.
GRHL2 was implicated in regulating cancer development. Our previous study demonstrated that knockdown GRHL2 in colorectal cancer (CRC) cells inhibited cell proliferation by targeting ZEB1. It is unclear whether GRHL2 expression may have diagnostic or prognostic value in colorectal carcinoma. Additionally, how GRHL2 is associated with the clinical features of colorectal carcinoma is not known. In current study, immunohistochemistry stains were performed to examine GRHL2 in 171 colorectal cancers and paired normal colon mucosa. The prognostic value of GRHL2 was investigated in a retrospective cohort study with a five-year follow-up. The effects of GRHL2 on cell growth in vitro and in vivo were explored by GRHL2 over-expressing in HT29 and SW620 CRC cells. Further, the regulation of cell cycle and proliferation proteins by GRHL2 were assessed by flow cytometry and western blot. We found that GRHL2 was over-expressed in CRC tissues, and played an important role in CRC tumorigenesis. GRHL2 expression positively correlated with tumor size and TNM stage. Kaplan-Meier analysis showed that GRHL2 was an independent prognostic factor for both overall survival and recurrence-free survival. Ectopic over-expression of GRHL2 in CRC cell line HT29 and SW620 induced an increase of cellular proliferation in vitro and promoting tumor growth in vivo. The acquisition of GRHL2 regulated cell cycle and modulates the expression of proliferation proteins p21, p27, cyclin A and cyclin D1. Together, our findings reveal GRHL2 can be used as a novel predictive biomarker and represent a potential therapeutic target against CRC.
GRHL2 被认为参与调控癌症的发生发展。我们之前的研究表明，在结直肠癌细胞中敲低 GRHL2 可以通过靶向 ZEB1 抑制细胞增殖。目前尚不清楚 GRHL2 在结直肠癌中的表达是否具有诊断或预后价值。此外，GRHL2 与结直肠癌临床特征的关系尚不清楚。在本研究中，通过免疫组织化学染色检测了 171 例结直肠癌组织和配对的正常结肠黏膜中的 GRHL2。通过对具有 5 年随访的回顾性队列研究，研究了 GRHL2 的预后价值。通过在 HT29 和 SW620 CRC 细胞中过表达 GRHL2 ，研究了 GRHL2 对细胞体外和体内生长的影响。进一步通过流式细胞术和 Western blot 评估了 GRHL2 对细胞周期和增殖蛋白的调节作用。我们发现，GRHL2 在 CRC 组织中过表达，并在 CRC 肿瘤发生中发挥重要作用。GRHL2 表达与肿瘤大小和 TNM 分期呈正相关。Kaplan-Meier 分析表明，GRHL2 是总生存期和无复发生存期的独立预后因素。在 CRC 细胞系 HT29 和 SW620 中过表达 GRHL2 ，可体外诱导细胞增殖增加，并促进体内肿瘤生长。获得的 GRHL2 调节细胞周期，并调节增殖蛋白 p21、p27、周期蛋白 A 和周期蛋白 D1 的表达。总之，我们的研究结果表明，GRHL2 可作为一种新的预测生物标志物，并代表针对 CRC 的潜在治疗靶点。
