REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis

被引:55
作者
Astrosini, Christian [2 ]
Roeefzaad, Claudia [2 ]
Dai, Yi-Yang [2 ]
Dieckgraefe, Brian K. [3 ]
Joens, Thomas [4 ]
Kemmner, Wolfgang [1 ]
机构
[1] Max Delbruck Ctr Mol Med, Surg Oncol Res Grp, D-13125 Berlin, Germany
[2] Robert Rossle Hosp, Clin Surg & Surg Oncol, Berlin, Germany
[3] Washington Univ, Sch Med, Siteman Canc Ctr, Div Gastroenterol, St Louis, MO USA
[4] Ctr Anat, Inst Integrat Neuroanat, Berlin, Germany
关键词
colorectal cancer; prognostic factors; peritoneal carcinomatosis; REG1A;
D O I
10.1002/ijc.23466
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
By expression profiling of early staged colon carcinomas, we found regenerating islet-derived 1 alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REGIA expression was quantified in another colorectal cancer (CRC) patient cohort by Taqman PCR. Aside from tumor and normal tissue from 63 nonpretreated CRC patients, 31 mucosa biopsies from healthy individuals as well as 22 adenomas were included in the investigation. REG1A was significantly upregulated in tumor specimens (p < 0.001) and adenoma (p < 0.01) as compared to normal colorectal tissue. REG1A expression in normal peritumoral tissue in turn proved to be significantly elevated compared to mucosa from healthy individuals (p < 0.01). Determination of REG1A expression might be useful for early tumor diagnosis with a sensitivity of 90.6%, and a specificity of 77.9%. REG1A expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.01). Moreover, REG1A turned out to be a significant predictor of disease-free survival (p < 0.05). In conclusion, we present evidence that REG1A is a molecular marker of prognostic value and is associated with peritoneal carcinomatosis in CRC. REG1A turned out to be already significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REGIA. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码:409 / 413
页数:5
相关论文
共 21 条
[1]   Metastasis genes: A progression puzzle [J].
Bernards, R ;
Weinberg, RA .
NATURE, 2002, 418 (6900) :823-823
[2]   Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas [J].
Bishnupuri, KS ;
Luo, QZ ;
Murmu, N ;
Houchen, CW ;
Anant, S ;
Dieckgraefe, BK .
GASTROENTEROLOGY, 2006, 130 (01) :137-149
[3]   Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes [J].
Bishnupuri, Kumar S. ;
Luo, Qizhi ;
Korzenik, Joshua R. ;
Henderson, Jeffrey O. ;
Houchen, Courtney W. ;
Anant, Shrikant ;
Dieckgraefe, Brian K. .
CANCER BIOLOGY & THERAPY, 2006, 5 (12) :1714-1720
[4]   Alteration of gene expression in normal-appearing colon mucosa of APCmin mice and human cancer patients [J].
Chen, LC ;
Hao, CY ;
Chiu, YSY ;
Wong, P ;
Melnick, JS ;
Brotman, M ;
Moretto, J ;
Mendes, F ;
Smith, AP ;
Bennington, JL ;
Moore, D ;
Lee, NM .
CANCER RESEARCH, 2004, 64 (10) :3694-3700
[5]  
Dieckgraefe BK, 2002, J INVEST MED, V50, P421, DOI 10.1136/jim-50-06-02
[6]   Determination of molecular marker expression can predict clinical outcome in colon carcinomas [J].
Galizia, G ;
Lieto, E ;
Ferraraccio, F ;
Orditura, M ;
De Vita, F ;
Castellano, P ;
Imperatore, V ;
Romano, C ;
Ciardiello, F ;
Agostini, B ;
Pignatelli, C .
CLINICAL CANCER RESEARCH, 2004, 10 (10) :3490-3499
[7]   Clinical relevance of sialyltransferases ST6GAL-I and ST3GAL-III in gastric cancer [J].
Gretschel, S ;
Haensch, W ;
Schlag, PM ;
Kemmner, W .
ONCOLOGY, 2003, 65 (02) :139-145
[8]   Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment [J].
Gross, DJ ;
Weiss, L ;
Reibstein, I ;
van den Brand, J ;
Okamoto, H ;
Clark, A ;
Slavin, S .
ENDOCRINOLOGY, 1998, 139 (05) :2369-2374
[9]   Molecular prognostics in colorectal cancer [J].
Kahlenberg, MS ;
Sullivan, JM ;
Witmer, DD ;
Petrelli, NJ .
SURGICAL ONCOLOGY-OXFORD, 2003, 12 (03) :173-186
[10]   Tissue microarrays for high-throughput molecular profiling of tumor specimens [J].
Kononen, J ;
Bubendorf, L ;
Kallioniemi, A ;
Bärlund, M ;
Schraml, P ;
Leighton, S ;
Torhorst, J ;
Mihatsch, MJ ;
Sauter, G ;
Kallioniemi, OP .
NATURE MEDICINE, 1998, 4 (07) :844-847