title: Prognostic and predictive potential molecular biomarkers in colon cancer.
abstract: An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.
authors.affiliation: Molecular biology and biobanking laboratory, Rntech, Bucharest, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Nastase
authors.forename: L
authors.initials: L
authors.lastname: Pâslaru
authors.forename: A M
authors.initials: AM
authors.lastname: Niculescu
authors.forename: M
authors.initials: M
authors.lastname: Ionescu
authors.forename: T
authors.initials: T
authors.lastname: Dumitraşcu
authors.forename: V
authors.initials: V
authors.lastname: Herlea
authors.forename: S
authors.initials: S
authors.lastname: Dima
authors.forename: C
authors.initials: C
authors.lastname: Gheorghe
authors.forename: V
authors.initials: V
authors.lastname: Lazar
authors.forename: I
authors.initials: I
authors.lastname: Popescu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D026281:DEFICIENS Protein / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000032:analysis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D026281:DEFICIENS Protein; D016209:Interleukin-8; D012333:RNA, Messenger; C506895:SPP1 protein, human; D053495:Osteopontin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7