Associations between matrix metalloproteinase, tissue inhibitor of metalloproteinase and collagen expression levels in the adjacent rectal tissue of colorectal carcinoma patients

Abstract

As the commonest type of cancer in Europe and the third most common type of cancer worldwide, colorectal carcinoma (CRC) poses a challenge for numerous scientific studies. At present, the cause of this disease is remains to be elucidated, but early diagnosis is only one solution to prevent serious health complications. As a structural scaffold, the extracellular matrix (ECM) is in direct contact with tumour cells and significantly interferes with tumour progression. During the process of tumorigenesis, the ECM undergoes structural changes in which collagens serve an important role. Their life cycle is regulated by proteolytic enzymes called matrix metalloproteinases (MMPs), which are controlled by tissue inhibitors of metalloproteinases (TIMPs). The present study analysed the gene expression of MMPs (MMP1-2-8-10-13), TIMPs (TIMP1-2-4) and collagens (COL1A1 and COL3A1) and the correlation with biochemical parameters in the adjacent rectal tissue (ART) of patients with CRC. The patients who underwent standard neoadjuvant pre-therapy showed increased concentrations of collagen in the normal ART. The mRNA levels of COL3A1, TIMP1 and TIMP2 were significantly higher in the ART of CRC patients (with or without pre-therapy) when compared with the control group. This finding suggested that TIMPs served an important role in the regulation of MMPs and in the modification of collagen content in the ECM. Despite the small data set, the present study provided insights into the transcriptomic relationships between the individual genes that are an integral part of the ECM.

Identification of GUCA2A and COL3A1 as prognostic biomarkers in colorectal cancer by integrating analysis of RNA-Seq data and qRT-PCR validation

“…Furthermore to gastric cancer, research results from several researchers have revealed that many collagen-encoding genes, including COL1A2 and COL3A1 had higher expression levels in pancreatic cancer 88 , thyroid cancer 89 and esophageal cancer 90 . Dibdiakova et al’s 91 results demonstrated that COL3A1 expression was significantly higher in CRC tissues compared to normal tissues, are consistent with the results of experiments from our findings. According to Tang et al 56 COL3A1 has been demonstrated to be overexpressed in stage IV colorectal cancer and to be significantly downregulated in lung metastasis samples compared to liver metastasis.…”

Genome-wide interaction analysis of folate for colorectal cancer risk

“…TIMP4 is a member of a family of extracellular matrix metalloproteinase inhibitors that has been shown to modulate processes such as cell differentiation, proliferation, and apoptosis [ 74 ]. TIMP4 is overexpressed in several cancers, including colorectal, and its expression was found to correlate with longer patient survival (in rectal cancer) [ 75 , 76 ].…”

Relationship between the Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Brain Tumors

“…The disruption of the extracellular matrix (ECM) is crucial for tumor mass growth and cell invasion, creating space for malignant cells to migrate [ 14 ]. The matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a pivotal role in this process, not limited to CNS tissue [ 15 , 16 ]. The MMP family comprises 23 endopeptidases that catalyze the degradation of the ECM and the basal membrane [ 17 ].…”