Proteomic approach to identify biomarkers for invasive cervix cancer - a prospective pilot study

Purpose of Investigation: Cervical cancer (CC) is the second most common cancer of women worldwide and a leading cause of mortality. Unfortunately, this disease has no current viable serum biomarkers capable of diagnosing CC or predicting prognosis. The present authors' objective was to examine novel serum biomarkers capable of identifying patients with invasive CC and determine their utility in monitoring disease status. Materials and Methods: In this IRB approved prospective study, luminex bead array was used to measure 18 different serum protein concentrations in CC patients (n=23), women with precancerous lesions (CIN2-3) (n=20) and patients with normal cervical cytology (n=20). CC patients had blood samples drawn within 30 days of diagnosis and repeat samples post-completion of therapy. MMP7 expression was confirmed by immunohistochemistry (IHC) and scored independently by two pathologists. Results: Multiple proteins had different levels in CC, controls, and CIN (p < 0.05). MMP7 was most promising for identifying invasive cancer (sensitivity of 88.9%, specificity 95%, p < 0.001). IHC confirmed MMP7 expression in invasive CC. MMP7 serum levels were an indicator for progression-free survival (PFS) (HR 3.82, CI: 1.10-13.29, p = 0.025) and overall survival (OS) (HR 7.96, CI: 0.91-69.32, p = 0.03). Conclusion: MMP7 serum concentration was altered when comparing CC, controls, and CIN2-3, and shows potential as being a future biomarker for both identifying invasive CC and patient prognosis. Based on this study, MMP7 warrants further investigation as a biomarker of invasive CC.