Serum Matrix metalloproteinase-9 (MMP-9) can help identify patients with papillary thyroid cancer at high risk of persistent disease: Value and limitations of a potential marker of neoplasia

Abstract

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. In thyroid cancer expression levels correlate with aggressiveness but data on peripheral MMP-9 levels are less definitive. OBJECTIVE: Prospective study evaluating serum MMP-9 in the diagnosis and prognosis of papillary thyroid cancer. METHODS: Serum samples of MMP-9 were drawn before surgery in 185 consecutively enrolled patients with nodular thyroid disease, stratified on pathology as benign disease (N= 88) and papillary thyroid cancer (N= 97). Serum MMP-9 was measured by an immunometric assay. RESULTS: MMP-9 levels were not different between benign vs malignant pathology (p= 0.3). In papillary thyroid cancer there was no significant difference in MMP-9 levels between histologies, TNM stage and invasive/non-invasive cancers. High-risk patients with multiple features of aggressiveness had significantly higher MMP-9 levels compared to low-intermediate risk patients (767.5 ± 269.2 ng/ml vs 563.7 ± 228.4 ng/ml, p= 0.019). A cut-off of 806 ng/ml distinguished high from low-intermediate risk patients with a sensitivity of 60% and a specificity of 87.36%, p= 0.018. In patients with available follow-up data (N= 78), MMP-9 was higher in patients who required ⩾ 2 doses of 131I therapy (p= 0.009) and in those with biochemical evidence of persistent disease/who required additional therapy to achieve disease-free status (p= 0.017). CONCLUSION: Serum MMP-9 is not useful in the diagnosis of PTC, but preliminary data shows that high pre-surgical serum MMP-9 levels may identify patients at higher risk of persistent disease who require intensive treatment. Large volume prospective studies are required to confirm this observation.

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

“…Our network meta-analysis of six studies (418 PTC patients, 221 benign diseases, 121 controls) using frequentist methods found that patients with PTC had significantly increased serum/plasma MMP9 versus both benign disease (SMD: 3.19, 95% CI: 2.84-3.55) and healthy controls (SMD: 3.13, 95% CI: 2.76-3.50) (Figure 11B). However, serum MMP9 levels were not different between benign and malignant pathology in two studies [73,76], highlighting the need to account for confounders. Data on circulating miR-145 levels in TC patients is limited, representing an area requiring further investigation.…”

“…Data on circulating miR-145 levels in TC patients is limited, representing an area requiring further investigation. In addition to tissue samples, several studies analyzed MMP9 levels in body fluids of thyroid cancer patients [65,[72][73][74][75][76]. Multiple studies have reported significantly higher serum/plasma MMP9 levels in PTC patients than those with benign thyroid diseases and healthy controls.…”

“…Several studies have examined the associations between MMP9 expression levels and clinicopathological parameters reflective of TC progression and prognosis (Table 6) [23,[61][62][63][64]73,77,78]. Higher MMP9 expression has been consistently associated with the presence of lymph node metastasis compared to PTC without metastasis in multiple studies [21,22,62,65,67,79,80].…”

The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma

“…4. The study uses serums as samples, which may provide different results from plasma samples because of coagulants and anticoagulants [106].…”

The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update

“…Serum MMP-9 levels measured using an immunometric assay were evaluated in subjects with PTC in a case-control study that concluded that although serum MMP-9 is not helpful in the diagnosis of PTC, a high pre-surgical level might be a prognostic factor that could dictate the treatment aggressiveness [ 60 ]. In a recent study that investigated the role of MMP-9 promoter −1562C/T functional SNP in the risk of developing PTC, the T allele was found significantly more frequently in subjects with PTC (17.5% vs. 10.1%, p = 0.019) [ 61 ].…”