Li Wei, Jiang Liang-Jun, Zhou Xiao-Jun, Lu Xian-Zhou, Liu Long-Fei, Wang Song
Department of General Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China.
Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China.
Oncol Lett. 2019 Feb;17(2):1974-1979. doi: 10.3892/ol.2018.9755. Epub 2018 Nov 23.
The present study aimed to investigate the association of the invasiveness of colon cancer (CC) with the expression of CCAAT/enhancer binding protein α (C/EBPα). Immunohistochemistry was performed to determine the expression of C/EBPα in the cancer and adjacent tissue samples from 48 patients with CC. A pCDGFP-C/EBPα eukaryotic expression vector was constructed, and a wound-healing assay was performed to observe the effect of transfection on the migration of SW480 cells. In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. Immunohistochemistry analysis demonstrated that the rate of low C/EBPα expression in normal tissue was 6.25%, whereas the rate in CC tissues was 68.75%; this difference was statistically significant (P<0.05). The patients with lower C/EBPα expression exhibited statistically larger tumor diameters, more advanced tumor-node-metastasis (TMN) stages and a greater likelihood of lymph node metastasis. The overexpression of C/EBPα significantly reduced the mobility of SW480 cells, and the expression of KLF5, MMP-2 and MMP-9 was reduced, whereas the expression of ECD was increased. In conclusion, C/EBPα was downregulated in CC tissue samples, and associated with the TMN stage and metastasis of CC; in addition, the overexpression of C/EBPα significantly reduced the invasiveness of CC cells. This may be significant for the diagnosis and treatment of CC in the future.
本研究旨在探讨结肠癌(CC)的侵袭性与CCAAT/增强子结合蛋白α(C/EBPα)表达之间的关联。采用免疫组织化学法检测48例CC患者癌组织及癌旁组织样本中C/EBPα的表达。构建pCDGFP-C/EBPα真核表达载体,并进行伤口愈合试验以观察转染对SW480细胞迁移的影响。此外,转染后检测包括Kruppel样因子5(KLF5)、基质金属肽酶(MMP)-2、MMP-9和E-钙黏蛋白(ECD)在内的肿瘤侵袭相关蛋白的表达水平。免疫组织化学分析表明,正常组织中C/EBPα低表达率为6.25%,而CC组织中为68.75%;差异具有统计学意义(P<0.05)。C/EBPα表达较低的患者肿瘤直径在统计学上更大,肿瘤-淋巴结-转移(TMN)分期更高,发生淋巴结转移的可能性更大。C/EBPα的过表达显著降低了SW480细胞的迁移能力,KLF5、MMP-2和MMP-9的表达降低,而ECD的表达增加。总之,C/EBPα在CC组织样本中表达下调,与CC的TMN分期和转移相关;此外,C/EBPα的过表达显著降低了CC细胞的侵袭性。这可能对未来CC的诊断和治疗具有重要意义。