Clinical Value Of OPN And MMP-9 In Evaluating The Sensitivity Of Chemoradiotherapy In Advanced Cervical Cancer

OBJECTIVE The aim of this study was to investigate the expression of osteopontin(OPN)and metalloproteinase-9(MMP-9)in cervical cancer patients with different chemoradiotherapy-sensitivity and evaluate the feasibility of using them as sensitive biomarkers of chemoradiotherapy.METHODS Clinical chemoradiotherapy-sensitivity was evaluated in 133 patients with stage ⅡB-ⅢB cervical squamous cell carcinoma accepted concurrent chemoradiotherapy.Treatment response was evaluated.Patients who achieved complete remission(CR)were classified as chemoradiotherapy-sensitive group.Other patients achieved partial remission(PR),improvement(MR)or progression of disease(PD)were classified as chemoradiotherapy-resistant group.The expression of OPN in cervical cancer tissues were detected by immunohistochemistry.Serum OPN and MMP-9 levels were measured by enzyme-linked immunosorbent assay(ELISA).The receiver operating characteristic(ROC)curves were constructed and the area under the curve(AUC)was calculated.Progression-free survival(PFS),overall survival(OS)were also evaluated.RESULTS Immunohistochemical analysis showed high expression of OPN in 91.67%(n=12)of chemoradiotherapy-resistant group and 57.85% of chemoradiotherapy-sensitive group(n=121)were(P=0.022).ELISA analysis showed high serum OPN expression rates were 100% and 42.28%,respectively(P=0.000).The overexpression of OPN was associated with the FIGO stage,tumor size,and chemoradiotherapy-sensitivity(P=0.027、0.016、0.022).The high serum OPN was associated weith the FIGO stage,tumor size,and chemoradiotherapy-sensitivity(P=0.018、0.011、0.000).The percentage of patients with high serum MMP-9 level in the chemoradiotherapy-resistant group was significantly higher than those in the chemoradiotherapy-sensitive group(83.33% vs.50.41%,P=0.002).Higher MMP-9 levels were correlated with FIGO stage Ⅲ,larger tumors,poor pathological grade and chemoradiotherapy-resistance(P<0.05 Pearsonχ2 test).Impact factors of PFS included FIGO staging,chemoradiotherapy sensitivity,serum MMP-9 and serum OPN levels by multivariate analysis(P=0.009、0.001、0.037 and 0.018,respectively).However,tissue OPN expression was not related with PFS(P=0.373).Factors related to OS including FIGO staging,chemoradiotherapy sensitivity and serum OPN levels(P=0.038,0.004,0.031).Interesting,neither tissue OPN expression nor serum MMP-9 level was found to be correlated with overall survival(P=0.585,0.183,respectively).Spearman analysis that serum OPN levels were positively correlated with MMP-9 levels(P<0.05,r=0.481).The AUC of OPN,MMP-9,and combined measurement was 0.759,0.747,and 0.851,respectively.Serum OPN,at given sensitivity of 73.7%,had a specificity of 69.1% in cervical cancer.The sensitivities and the specificity of MMP-9 were 78.9% and 57.7%,respectively.The combination of the two markers of sensitivity and specificity were 73.7% and 85.6%,respectively.CONCLUSION OPN expression is highly correlated with poor prognosis in patients with cervical cancer treated with chemoradiotherapy.Serum OPN level could be a useful and specific marker for judging prognosis and formulating individualized treatment.Combined measurements of serum OPN and MMP-9 increased the diagnostic specificity.