Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer

Abstract

Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at – 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at − 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.

Extracellular matrix changes in colorectal carcinoma and correlation with lymph node metastasis

“…In contrast, MMP-9 up-regulation has also been described in CRC precursor lesions, which may indicate its use as a biomarker of early CRC diagnosis [22,36]. Some studies have presented conflicting results regarding the role of MMP-9 expression in the prognosis in CRC patients [33][34][35][36].…”

“…Matrix metalloproteinases (MMP) are calcium-dependent zinc endopeptidases [21,22] and are physiologically involved in the degradation of ECM components, embryogenesis, reproduction, angiogenesis, bone development, wound healing, and cell migration [23]. Matrix metallopeptidase 9 (MMP-9) has its genetic locus on chromosome 20q11.2-q13.1 and is produced by epithelial cells, macrophages, granulocytes, T-cells, keratinocytes, dendritic cells, osteoblasts, and fibroblasts [24][25][26].…”

“…MMP is synthesized by tumor cells and stromal cells surrounding the neoplasia and can degrade the basal membranes, often the first step of carcinoma invasion. MMP facilitates tumor progression, including invasion, metastasis, growth, matrix remodeling, and angiogenesis, by increasing the concentration of vascular endothelial growth factor (VEGF) [22,23].…”

PathME: pathway based multi-modal sparse autoencoders for clustering of patient-level multi-omics data

“…Altogether CNVs demonstrate the strongest impact on the multi-omics pathway score learned for FGF signaling (Table S8), and CNVs in the metalloproteinase-9 (MMP9) gene are most impactful. The MMP9 level has been suggested as a biological predictor of prognosis in CRC [54] For cluster 4, a high contribution of the nuclear estrogen receptor (ER) activation pathway is determined. ER signaling including ER-α and ER-β is implicated in CRC pathogenesis and progression and it is considered as a potential preventive and therapeutic target [55].…”

A comprehensive investigation of colorectal cancer progression, from the early to late-stage, a systems biology approach

“…COL3A1 also has a role in metastasis and can stimulate proliferation via pi3k-akt axis [39]. MMP9 is a key factor in the reconstruction of ECM, invasion, and regulation of tumor microenvironment, and angiogenesis in colorectal cancer [40]. Furthermore, MMP2 has more than ten times expression in CRCs than healthy tissues.…”