MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer

Distant metastasis is the major cause of death in colorectal cancer (CRC) patients. To identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real‐time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real‐time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (p < 0.001). In Stages II and III CRC, patients with low expression showed worse disease‐free survival (p = 0.020). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in Stages II and III CRC (relative risk, 8.236; 95% confidence interval, 1.702–39.849 p = 0.009). Our study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients.

[1]  M. Somerfield,et al.  American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  D. Gotley,et al.  Two novel mucin genes down-regulated in colorectal cancer identified by differential display. , 1999, Cancer research.

[3]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[4]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[5]  M. Tsao,et al.  Expression profiling by microarrays in colorectal cancer (Review). , 2005, Oncology reports.

[6]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[7]  Baljit Singh,et al.  Oncogenic β-Catenin Is Required for Bone Morphogenetic Protein 4 Expression in Human Cancer Cells , 2002 .

[8]  J. Astola,et al.  Gene-expression profiling predicts recurrence in Dukes' C colorectal cancer. , 2005, Gastroenterology.

[9]  Y. Miki,et al.  Aurora kinase B is a predictive factor for the aggressive recurrence of hepatocellular carcinoma after curative hepatectomy , 2008, The British journal of surgery.

[10]  M. Yasuno,et al.  Expression of 5-lipoxygenase in human colorectal cancer. , 2006, World journal of gastroenterology.

[11]  T. Akiyama,et al.  Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer. , 2008, World journal of gastroenterology.

[12]  Gerhard Christofori,et al.  Cell adhesion and signalling by cadherins and Ig-CAMs in cancer , 2004, Nature Reviews Cancer.

[13]  D. Hirsch,et al.  Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression. , 1997, Biochemical and biophysical research communications.

[14]  L. Packer,et al.  Expression of the cell surface mucin gene family in adenocarcinomas. , 2004, International journal of oncology.

[15]  L. Lipton,et al.  Adjuvant therapies for colorectal cancer. , 2007, World journal of gastroenterology.

[16]  Emery H Bresnick,et al.  Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. , 2004, Molecular immunology.

[17]  A. Knudson,et al.  Optimized procedures for microarray analysis of histological specimens processed by laser capture microdissection , 2004, Journal of cellular physiology.

[18]  S. Rudman,et al.  Targeted therapy in colorectal carcinoma: more than a theory , 2008, Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.

[19]  F. Révillion,et al.  Prognostic Value of ERM Gene Expression in Human Primary Breast Cancers , 2004, Clinical Cancer Research.

[20]  Michael A. Hollingsworth,et al.  Mucins in cancer: protection and control of the cell surface , 2004, Nature Reviews Cancer.

[21]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[22]  David C. Atkins,et al.  Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  V. Gouyer,et al.  Architecture of the large membrane-bound mucins. , 2008, Gene.

[24]  W. Zimmermann,et al.  Down-regulation of carcinoembryonic antigen family member 2 expression is an early event in colorectal tumorigenesis. , 1997, Cancer research.

[25]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[26]  E. Wolski,et al.  Normalization strategies for cDNA microarrays. , 2000, Nucleic acids research.

[27]  T Tanaka,et al.  Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles. , 2001, Cancer research.

[28]  Daniel L. Hartl,et al.  GeneMerge - Post-genomic Analysis, Data Mining, and Hypothesis Testing , 2003, Bioinform..

[29]  B. Dieckgraefe,et al.  REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosis , 2008, International journal of cancer.

[30]  Katsuhiko Yanaga,et al.  Clinical Significance of TROP2 Expression in Colorectal Cancer , 2006, Clinical Cancer Research.

[31]  M. Weinstein,et al.  Cost‐effectiveness analysis of oxaliplatin compared with 5‐fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US , 2007, Cancer.

[32]  B. Wolpin,et al.  Systemic treatment of colorectal cancer. , 2008, Gastroenterology.

[33]  T R Fleming,et al.  Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  J. Burgess,et al.  New developments in the analysis of gene expression , 2000, Redox report : communications in free radical research.

[35]  J Quackenbush,et al.  Effects of ischemia on gene expression. , 2001, The Journal of surgical research.

[36]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[37]  T. Hickish,et al.  Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. , 2004, The New England journal of medicine.

[38]  Baljit Singh,et al.  Oncogenic beta-catenin is required for bone morphogenetic protein 4 expression in human cancer cells. , 2002, Cancer research.

[39]  J. Hardcastle,et al.  Colorectal cancer , 1993, Europe Against Cancer European Commission Series for General Practitioners.