Yusup Akram, Huji Bailikezi, Fang Cheng, Wang Fei, Dadihan Tuerxunjiang, Wang Hai-Jiang, Upur Halmurat
Akram Yusup, Bailikezi Huji, Hai-Jiang Wang, Department of Gastrointestinal Surgery and Record Room, Affiliated Tumor Hospital, Xin Jiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China.
World J Gastroenterol. 2017 Jan 7;23(1):110-120. doi: 10.3748/wjg.v23.i1.110.
To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival.
This study examined the expression of TFF1, TFF3 and TWIST1 in a total of 75 tumor samples, 47 matched normal samples (15 cm from the lesion margin), 30 metastatic lymph nodes, and 10 liver metastatic cancer samples from patients with CRC. The relationship was then analyzed between the protein expression and different clinical records. TFF1, TFF3, TWIST1,E-cadherin, vimentin and β-catenin mRNA and protein expression levels were measured in colon cancer cell lines with different metastatic potentials (HIEC, HT29, SW620, and LoVo cells), and the correlation of the expression levels with epithelial-mesenchymal transition (EMT) was discussed.
It was found that 66.7% (50/75), 78.7% (59/75) and 54.7% (41/75) of tumor tissue samples exhibited positive staining for TFF1, TFF3 and TWIST1 and so did 27.3% (13/47), 100% (47/47) and 17% (8/47) of adjacent normal colorectal tissues. Compared with adjacent normal tissues, significant differences were found in the expression of all three proteins in different cancerous tissues ( < 0.05). Higher expression of TFF3 and TWIST1 was significantly correlated with lymph node metastasis ( = 0.034, = 0.000), advanced stage ( = 0.031, = 0.003), and poorer survival ( = 0.042 for the TFF3 group, = 0.003 for the TWIST1 group). The expression of TFF3 and TWIST1 in cancer cell lines was higher than that in HIEC (a normal human intestinal epithelial cell line)( < 0.05), and the expression intensity demonstrated a tendency to rise with increased metastatic potential both at the protein and mRNA levels. However, TFF1 expression demonstrated the opposite tendency. It was also observed that the expression of E-cadherin and β-catenin tended to decrease while that of vimentin, TWIST1 and Snail tended to rise with the increase in metastatic potential.
The expression of TFF3 and TWIST1 might be associated with the survival of patients with CRC after curative resection and might be pivotal predictors of disease progression. TFF3 may be correlated to the invasiveness of CRC.
检测三叶因子（TFFs）和TWIST1在结直肠癌（CRC）中的表达，并分析它们与转移和生存的相关性。
本研究检测了75例肿瘤样本、47例配对的正常样本（距病变边缘15 cm）、30例转移淋巴结以及10例CRC患者的肝转移癌样本中TFF1、TFF3和TWIST1的表达。然后分析蛋白质表达与不同临床记录之间的关系。检测了具有不同转移潜能的结肠癌细胞系（HIEC、HT29、SW620和LoVo细胞）中TFF1、TFF3、TWIST1、E-钙黏蛋白、波形蛋白和β-连环蛋白的mRNA和蛋白质表达水平，并探讨了表达水平与上皮-间质转化（EMT）的相关性。
发现肿瘤组织样本中分别有66.7%（50/75）、78.7%（59/75）和54.7%（41/75）的TFF1、TFF3和TWIST1呈阳性染色，相邻正常结直肠组织中分别有27.3%（13/47）、100%（47/47）和17%（8/47）呈阳性染色。与相邻正常组织相比，不同癌组织中这三种蛋白的表达均有显著差异（<0.05）。TFF3和TWIST1的高表达与淋巴结转移（=0.034，=0.000）、晚期（=0.031，=0.003）及较差的生存率显著相关（TFF3组=0.042，TWIST1组=0.003）。癌细胞系中TFF3和TWIST1的表达高于HIEC（一种正常人肠上皮细胞系）（<0.05），且在蛋白质和mRNA水平上，表达强度均呈现出随转移潜能增加而升高的趋势。然而，TFF1的表达呈现相反趋势。还观察到，随着转移潜能的增加，E-钙黏蛋白和β-连环蛋白的表达趋于降低，而波形蛋白、TWIST1和Snail的表达趋于升高。
TFF3和TWIST1的表达可能与CRC根治性切除术后患者的生存相关，可能是疾病进展的关键预测指标。TFF3可能与CRC的侵袭性相关。
