title: Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients.
abstract: Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443 ng ml(-1) (IQR: 219-782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (chi(2)=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK. Nicholas.hurst@derbyhospitals.nhs.uk
authors.forename: N G
authors.initials: NG
authors.lastname: Hurst
authors.forename: D D
authors.initials: DD
authors.lastname: Stocken
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Keh
authors.forename: M J O
authors.initials: MJ
authors.lastname: Wakelam
authors.forename: T
authors.initials: T
authors.lastname: Ismail
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D020780:Matrix Metalloproteinase 9