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Background  The aim of the present study was to investigate the association between matrix metalloproteinase-9 (MMP-9) expression with BRAF V600E mutation and clinicopathological features, in Iranian papillary thyroid cancer (PTC) patients.    Methods  In total, 90 participants including 60 PTC patients (15 males and 45 females) and 30 individuals with benign multinodular goiter (MNG) (5 males and 25 females) which were confirmed by surgical pathology, were investigated. MMP-9 was evaluated at both mRNA and protein levels, using SYBR-Green Real-Time PCR and enzyme-linked immune sorbent assay (ELISA), respectively. BRAF V600E mutation was detected by sequencing.    Results  Mean age of PTC and MNG patients was 37.6 ± 12.6 and 48.1 ± 13.3 years, respectively ( P  = 0.001). BRAF V600E mutation was found in 24 of the 60 (40%) PTC cases, with mean tumor size of 1.59 ± 1.20 cm. MMP-9 mRNA levels were elevated in tumoral compared to the adjacent non-tumoral tissues ( P  = 0.039); moreover, this rise was also observed in PTC patients compared to MNG patients ( P  = 0.001). The mRNA levels of MMP-9 increased in patients aged≥45 years ( P  = 0.015), those with lymphovascular invasion ( P  = 0.003), and higher tumor stages (III and IV) ( P  = 0.011). The protein level of MMP-9 increased in tumoral compared to adjacent non-tumoral tissues ( P  < 0.001); this increase was also found in PTC patients compared to MNG participants ( P  = 0.004). MMP-9 protein level was higher in patients aged≥45 years ( P  = 0.001), those with lymphovascular invasion ( P  = 0.036) and higher TNM stages (III and IV) ( P  = 0.001). Area under the ROC curve (AUC) was 0.70 (95%CI: 0.57–0.83,  P  = 0.003), with 91.4% sensitivity and 51.9% specificity at the cutoff value of 0.50.    Conclusion  The mRNA and protein levels of MMP-9 had no association with BRAF V600E mutation in Iranian PTC patients. These levels were associated with age, TNM stages, and lymphovascular invasion, being defined as malignant factors. Thus, elevated levels of MMP-9 in PTC patients compared to MNG participants illustrated that it can be used as a potential biomarker to differentiate PTC patients from those with MNG.

The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer