Prognostic and predictive potential molecular biomarkers in colon cancer

被引:0
作者
Nastase, A. [2 ]
Paslaru, L. [1 ]
Niculescu, A. M. [2 ]
Ionescu, M. [3 ]
Dumitrascu, T. [3 ]
Herlea, V. [4 ]
Dima, S. [3 ]
Gheorghe, C. [5 ]
Lazar, V. [6 ]
Popescu, I. [3 ]
机构
[1] Univ Med & Pharm Carol Davila, Postgrad Dept Biochem, Bucharest, Romania
[2] Rntech, Mol Biol & Biobanking Lab, Bucharest, Romania
[3] Fundeni Clin Inst, Ctr Gen Surg & Liver Transplantat, Bucharest, Romania
[4] Fundeni Clin Inst, Dept Pathol, Bucharest, Romania
[5] Fundeni Clin Inst, Ctr Gastroenterol & Hepatol, Bucharest, Romania
[6] Gustave Roussy Inst Cancerol, Villejuif, France
关键词
colon cancer; biomarkers; qPCR; COLORECTAL-CANCER; MATRIX METALLOPROTEINASES; GENOMIC INSTABILITY; TUMOR-METASTASIS; CARCINOMA CELLS; EXPRESSION; OSTEOPONTIN; INTERLEUKIN-8; ANGIOGENESIS; PROGRESSION;
D O I
暂无
中图分类号
R61 [外科手术学];
学科分类号
摘要
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 DEFA13 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 metastsis 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 DEFA5, 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.
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页码:177 / 185
页数:9
相关论文
共 44 条
[1]   CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER [J].
AALTONEN, LA ;
PELTOMAKI, P ;
LEACH, FS ;
SISTONEN, P ;
PYLKKANEN, L ;
MECKLIN, JP ;
JARVINEN, H ;
POWELL, SM ;
JEN, J ;
HAMILTON, SR ;
PETERSEN, GM ;
KINZLER, KW ;
VOGELSTEIN, B ;
DELACHAPELLE, A .
SCIENCE, 1993, 260 (5109) :812-816
[2]   Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin) [J].
Agnihotri, R ;
Crawford, HC ;
Haro, H ;
Matrisian, LM ;
Havrda, MC ;
Liaw, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (30) :28261-28267
[3]  
Agrawal D, 2002, J NATL CANCER I, V94, P513
[4]   Down-regulation of CXCL-1 inhibits growth of colorectal liver metastases [J].
Bandalalli, Obul R. ;
Goeppinger, Stephan M. ;
Gaida, Matthias ;
Wente, Moritz ;
Schirmacher, Peter ;
Brand, Karsten .
CYTOKINE, 2008, 43 (03) :325-325
[5]  
Dhawan P, 2002, J LEUKOCYTE BIOL, V72, P9
[6]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767
[7]   Molecular circuits of solid tumors: prognostic and predictive tools for bedside use [J].
Ferte, Charles ;
Andre, Fabrice ;
Soria, Jean-Charles .
NATURE REVIEWS CLINICAL ONCOLOGY, 2010, 7 (07) :367-380
[8]   Genomic instability and colon cancer [J].
Grady, WM .
CANCER AND METASTASIS REVIEWS, 2004, 23 (1-2) :11-27
[9]  
Half E, 2009, EXPERT OPIN PHARMACO, V10, P211, DOI [10.1517/14656560802560153 , 10.1517/14656560802560153]
[10]   UBIQUITOUS SOMATIC MUTATIONS IN SIMPLE REPEATED SEQUENCES REVEAL A NEW MECHANISM FOR COLONIC CARCINOGENESIS [J].
IONOV, Y ;
PEINADO, MA ;
MALKHOSYAN, S ;
SHIBATA, D ;
PERUCHO, M .
NATURE, 1993, 363 (6429) :558-561