Abstract
BackgroundA significant proportion of newly diagnosed patients with cutaneous squamous cell carcinoma (cSCC) have metastasis and eventually die of the disease, necessitating the exploration of novel biomarkers for early detection of cSCC aggressiveness, risk assessment and monitoring. Matrix metalloproteinase-13 (MMP-13) has been implicated in cSCC pathogenesis. Serum MMP-13 levels have been shown to predict survival in patients with esophageal SCC, but their diagnostic value for cSCC has not been explored.MethodsWe conducted a case-control study to examine serum MMP-13 as a biomarker for cSCC. Patients with cSCC undergoing surgical resection and health controls undergoing plastic surgery were recruited. ELISA for measurement of serum MMP-13 and immunohistochemistry for detection of tissue MMP-13 were performed, and the results were compared between the case and the control group, and among different patient groups. ROC curve analysis was performed to determine the diagnostic value of serum MMP-13 levels.ResultsThe ratio of male to female, and the age between the case (n = 77) and the control group (n = 50) were not significantly different. Patients had significantly higher serum MMP-13 levels than healthy controls. Subjects with stage 3 cSCC had markedly higher serum MMP-13 levels than those with stage 1 and stage 2 cSCC. Patients with invasive cSCC had remarkably higher serum MMP-13 than those with cSCC in situ. Post-surgery serum MMP-13 measurement was done in 12 patients, and a significant MMP-13 decrease was observed after removal of cSCC. Tumor tissues had a remarkably higher level of MMP-13 than control tissues. Serum MMP-13 predicted the presence of invasive cSCC with an AUC of 0.87 (95% CI [0.78 to 0.95]) for sensitivity and specificity of 81.7 and 82.4%, respectively for a cut-off value of 290 pg/mL. Serum MMP-13 predicted lymph node involvement with an AUC of 0.94 (95% CI [0.88 to 0.99]) for sensitivity and specificity of 93.8 and 88.5%, respectively for a cut-off value of 430 pg/mL.ConclusionSerum MMP-13 might serve as a valuable biomarker for early detection of cSCC invasiveness and monitoring of cSCC progression.
Highlights
A significant proportion of newly diagnosed patients with cutaneous squamous cell carcinoma have metastasis and eventually die of the disease, necessitating the exploration of novel biomarkers for early detection of cSCC aggressiveness, risk assessment and monitoring
Higher levels of serum Matrix metalloproteinase-13 (MMP-13) were detected in subjects with lymph node metastasis compared with those without lymph node metastasis (Fig. 2 c)
Post-surgery measurement of serum Matrix metalloproteinases (MMPs)-13 was performed in 12 patients, which showed a marked decrease of serum MMP-13 concentrations after the removal of cSCC (523.0 ± 231.4 pg/ml prior-surgery versus 296.4 ± 92.6 pg/ml post-surgery, p < 0.001)
Summary
A significant proportion of newly diagnosed patients with cutaneous squamous cell carcinoma (cSCC) have metastasis and eventually die of the disease, necessitating the exploration of novel biomarkers for early detection of cSCC aggressiveness, risk assessment and monitoring. Matrix metalloproteinase-13 (MMP-13) has been implicated in cSCC pathogenesis. Serum MMP-13 levels have been shown to predict survival in patients with esophageal SCC, but their diagnostic value for cSCC has not been explored. Cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC) account for approximately 80 and 20% of nonmelanoma skin cancer (NMSC), respectively [24, 25]. MMP-13, termed collagenase-3 responsible for cleavage of fibrillar collagens, gelatin and fibronectin, is not detectable in intact normal skin [30], but its expression has been shown in tumor tissues from patients with cSCC and SCC of the head and neck [30,31,32,33,34]. Serum MMP-13 as a diagnostic marker for cSCC has not been explored
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