title: SOX9 expression predicts relapse of stage II colon cancer patients.
abstract: The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment.
authors.affiliation: Department of Pathology, Herlev University Hospital, DK-2730 Herlev, Denmark; Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde, Denmark. Electronic address: maiken.lise.marcker.espersen@regionh.dk.
authors.forename: Maiken Lise
authors.initials: ML
authors.lastname: Marcker Espersen
authors.affiliation: Department of Pathology, Herlev University Hospital, DK-2730 Herlev, Denmark. Electronic address: dorte.linnemann@regionh.dk.
authors.forename: Dorte
authors.initials: D
authors.lastname: Linnemann
authors.affiliation: Department of Pathology, Herlev University Hospital, DK-2730 Herlev, Denmark. Electronic address: ib.jarle.christensen@regionh.dk.
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Department of Surgery, Køge University Hospital, DK-4600 Køge, Denmark. Electronic address: mahdi_alamili@hotmail.com.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Alamili
authors.affiliation: Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde, Denmark. Electronic address: troelsen@ruc.dk.
authors.forename: Jesper T
authors.initials: JT
authors.lastname: Troelsen
authors.affiliation: Department of Pathology, Herlev University Hospital, DK-2730 Herlev, Denmark. Electronic address: estrid.hoegdall@regionh.dk.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055758:SOX9 Transcription Factor / Q000032:analysis*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D045643:DNA Repair Enzymes
keywords: Biomarkers; Colon cancer; Mismatch repair deficiency; Recurrence; SOX9 transcription factor