Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19857-17411, Iran.
Faculty of Health and Wellbeing, Canterbury Christ Church University, Canterbury CT1 1QU, UK.
Genes (Basel). 2022 Apr 14;13(4):689. doi: 10.3390/genes13040689.
TGF-β signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-β canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-β-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p < 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p < 0.0001). This study showed that canonical TGF-β signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-β signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC.
TGF-β 信号通路促进肿瘤的发展，并控制着几个下游基因，如 CTGF 和 MMPs。本研究旨在探讨 CTGF 和 MMP-1 mRNA 表达与结直肠癌患者临床病理特征和生存率的关系。我们通过实时 PCR 检测了石蜡包埋肿瘤组织和相邻正常组织块（ADJ）中 CTGF 和 MMP-1 基因的表达水平。然后，通过免疫组织化学评估 TGF-β 经典途径中 Smad2 和 Smad4 蛋白的表达。最后，研究了 CTGF、MMP-1 和经典 TGF-β 信号通路与临床病理特征的相关性。与相邻正常组织相比，肿瘤中 MMP-1 和 CTGF 的表达水平更高。MMP-1 和 CTGF 的过表达水平与淋巴结转移、远处转移、肿瘤组织学分级、晚期和预后不良相关（p < 0.05）。此外，还观察到 MMP-1 的上调与肿瘤位置之间存在显著相关性。Smad2 和 Smad4 蛋白的上调也与淋巴结转移、远处转移、晚期和预后不良显著相关（p < 0.0001）。本研究表明，经典 TGF-β 信号通路调节 CTGF 和 MMP-1 的表达和 CRC 的进展。此外，TGF-β 信号及其下游基因可作为 CRC 靶向治疗的新型生物标志物和新方法。
