Differential expression and prognostic role of selected genes in colorectal cancer patients.

AIM Colorectal cancer (CRC) is one of the most common malignant diseases. The aim of our study was to describe the expression status of 12 selected candidate genes, by comparing paired samples of healthy colon mucosa and tumour tissues and to correlate obtained data with clinical and pathological features, with the goal of revealing associations for individual gene expressions and tumour behaviour. MATERIALS AND METHODS Samples from 53 patients with CRC were analyzed. Patients were divided into two groups based on the presence or absence of distant metastases at the time of primary tumour surgery. Expression levels were assessed by quantitative real-time polymerase chain reaction. RESULTS We found changes in the expression of 10 out of 12 analyzed genes. Four genes were significantly up-regulated in tumour tissues: leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5; p<0.001), collagen triple helix repeat containing 1 (CTHRC1; p<0.001), visinin-like 1 (VSNL1; p<0.001) and versican (VCAN; p=0.001). Six genes were down-regulated: destrin (DSTN; p=0.004), mesoderm induction early response 1, family member 3 (MIER3; p<0.001), acyl-CoA synthetase long-chain family member 5 (ACSL5; p=0.002), mitogen-activated protein kinase 1/ERK (MAPK1; p<0.001), claudin 23 (CLDN23; p<0.001) and solute carrier family 26 (sulfate transporter), member 2 (SLC26A2; p<0.001). We recorded longer overall survival (OS) in the group of patients with higher expression of VSNL1 (p=0.032). Patients with more pronounced down-regulation of CLDN23 had shorter OS (p=0.045). In the group of patients without distant metastases, longer OS and disease-free interval (DFI) were found for patients with higher SLC26A2 expression in tumour tissues (p=0.036 and p=0.011, respectively). In the same group, lower expression of VSNL1 in healthy tissue corresponded to a longer DFI (p=0.020), smaller decrease of SLC26A2 and ACSL5 meant longer DFI (p=0.041 and p=0.040, respectively), as did greater increase of LGR5 expression (p=0.026). CONCLUSION We identified differences in the expression of 10 genes in colorectal cancer tissue compared to healthy colon mucosa, and found prognostic significance for these changes which could be used for the development of a disease risk scoring system.

[1]  Jeffrey J Meyer,et al.  Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012. (5) , 2013 .

[2]  Alok K. Sharma,et al.  The SLC26 gene family of anion transporters and channels. , 2013, Molecular aspects of medicine.

[3]  F. Liu,et al.  CTHRC1 is associated with peritoneal carcinomatosis in colorectal cancer: a new predictor for prognosis , 2013, Medical Oncology.

[4]  Hans Clevers,et al.  In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration , 2013, Nature.

[5]  Jun Yu,et al.  Zinc-finger protein 331, a novel putative tumor suppressor, suppresses growth and invasiveness of gastric cancer , 2013, Oncogene.

[6]  P. Lichter,et al.  LGR5 is a Marker of Poor Prognosis in Glioblastoma and is Required for Survival of Brain Cancer Stem‐Like Cells , 2013, Brain pathology.

[7]  C. Chomienne,et al.  Regulation of the transcriptional activity of nuclear receptors by the MEK/ERK1/2 pathway. , 2012, Cellular signalling.

[8]  H. Xi,et al.  Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival , 2012, World Journal of Surgical Oncology.

[9]  A. denDekker,et al.  Rat Mcs1b is concordant to the genome-wide association-identified breast cancer risk locus at human 5q11.2 and MIER3 is a candidate cancer susceptibility gene. , 2012, Cancer research.

[10]  S. Kitano,et al.  Visinin‐like protein‐1 overexpression is an indicator of lymph node metastasis and poor prognosis in colorectal cancer patients , 2012, International journal of cancer.

[11]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of human colon and rectal cancer , 2012, Nature.

[12]  S. Goel,et al.  Evolvement of the treatment paradigm for metastatic colon cancer. From chemotherapy to targeted therapy. , 2012, Critical reviews in oncology/hematology.

[13]  C. Röcken,et al.  The Spatial Distribution of LGR5+ Cells Correlates With Gastric Cancer Progression , 2012, PloS one.

[14]  Andres J Klein-Szanto,et al.  The putative Tumor Suppressor VILIP-1 Counteracts Epidermal Growth Factor-Induced Epidermal-Mesenchymal Transition in Squamous Carcinoma Cells , 2012, PloS one.

[15]  G. Nepom,et al.  Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration. , 2012, Matrix biology : journal of the International Society for Matrix Biology.

[16]  P. Souček,et al.  The role of ABC transporters in progression and clinical outcome of colorectal cancer. , 2012, Mutagenesis.

[17]  L. Miao,et al.  Interleukin-11 Promotes the Progress of Gastric Carcinoma via Abnormally Expressed Versican , 2012, International journal of biological sciences.

[18]  C. Vela,et al.  Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer , 2012, BMC Clinical Pathology.

[19]  K. Braunewell.  The visinin-like proteins VILIP-1 and VILIP-3 in Alzheimer's disease—old wine in new bottles , 2012, Front. Mol. Neurosci..

[20]  N. Normanno,et al.  EGFR-targeted therapy. , 2011, Experimental cell research.

[21]  W. Samowitz,et al.  Epidermal growth factor receptor pathway mutations and colorectal cancer therapy. , 2011, Archives of pathology & laboratory medicine.

[22]  A. Fagan,et al.  Visinin‐like protein‐1: Diagnostic and prognostic biomarker in Alzheimer disease , 2011, Annals of neurology.

[23]  C. Kersten,et al.  Expression of the adult intestinal stem cell marker Lgr5 in the metastatic cascade of colorectal cancer. , 2011, International journal of clinical and experimental pathology.

[24]  Charles Swanton,et al.  Genetic prognostic and predictive markers in colorectal cancer , 2011, Nature Reviews Cancer.

[25]  C. Mathers,et al.  Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 , 2010, International journal of cancer.

[26]  Sabine Tejpar,et al.  Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. , 2010, The Lancet. Oncology.

[27]  M. Sakamoto,et al.  Overexpression of leucine‐rich repeat‐containing G protein‐coupled receptor 5 in colorectal cancer , 2010, Cancer science.

[28]  R. Kannagi,et al.  Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewisx expression and accelerates proliferation of colon cancer cells. , 2010, Cancer research.

[29]  C. Conti,et al.  VILIP-1 Expression In Vivo Results in Decreased Mouse Skin Keratinocyte Proliferation and Tumor Development , 2010, PloS one.

[30]  P. Morin,et al.  The claudins , 2009, Genome Biology.

[31]  T. Tsuruo,et al.  Acyl‐CoA synthetase as a cancer survival factor: its inhibition enhances the efficacy of etoposide , 2009, Cancer science.

[32]  S. Spiegl-Kreinecker,et al.  Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells , 2009, Molecular Cancer Therapeutics.

[33]  H. Mashimo,et al.  Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue , 2008, TheScientificWorldJournal.

[34]  C. Stournaras,et al.  Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells. , 2008, Experimental cell research.

[35]  Zsolt Tulassay,et al.  Diagnostic mRNA Expression Patterns of Inflamed, Benign, and Malignant Colorectal Biopsy Specimen and their Correlation with Peripheral Blood Results , 2008, Cancer Epidemiology Biomarkers & Prevention.

[36]  J. Barrett,et al.  Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  A. Bellacosa,et al.  VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival , 2008, PloS one.

[38]  M. Serrano-Ríos,et al.  Identification of a protective haplogenotype within CAPN10 gene influencing colorectal cancer susceptibility , 2007, Journal of gastroenterology and hepatology.

[39]  P. Tam,et al.  Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma. , 2007, Carcinogenesis.

[40]  P. Schirmacher,et al.  Regulation of enterocyte apoptosis by acyl-CoA synthetase 5 splicing. , 2007, Gastroenterology.

[41]  O. Topolcan,et al.  Dynamics of serum levels of tumour markers and prognosis of recurrence and survival after liver surgery for colorectal liver metastases. , 2007, Anticancer research.

[42]  M. Nelson,et al.  Profiling of selenomethionine responsive genes in colon cancer by microarray analysis , 2007, Cancer biology & therapy.

[43]  R. Lothe,et al.  Molecular Cancer Gene Expression Profiles of Primary Colorectal Carcinomas, Liver Metastases, and Carcinomatoses , 2022 .

[44]  Sarah Dennison,et al.  Calpains and Their Multiple Roles in Diabetes Mellitus , 2006, Annals of the New York Academy of Sciences.

[45]  A. Bassols,et al.  V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis , 2006, Laboratory Investigation.

[46]  D. Kletsas,et al.  The greatly increased amounts of accumulated versican and decorin with specific post-translational modifications may be closely associated with the malignant phenotype of pancreatic cancer. , 2006, Biochimica et biophysica acta.

[47]  M. Martinka,et al.  Aberrant Expression of Collagen Triple Helix Repeat Containing 1 in Human Solid Cancers , 2006, Clinical Cancer Research.

[48]  A. Lièvre,et al.  KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. , 2006, Cancer research.

[49]  Shiu-Ru Lin,et al.  Fatty acid metabolism pathway play an important role in carcinogenesis of human colorectal cancers by Microarray-Bioinformatics analysis. , 2006, Cancer letters.

[50]  S. L. Wong,et al.  Towards a proteome-scale map of the human protein–protein interaction network , 2005, Nature.

[51]  John Quackenbush,et al.  Synchronous global assessment of gene and protein expression in colorectal cancer progression. , 2005, Genomics.

[52]  L. Liaw,et al.  Collagen Triple Helix Repeat Containing 1, a Novel Secreted Protein in Injured and Diseased Arteries, Inhibits Collagen Expression and Promotes Cell Migration , 2005, Circulation research.

[53]  Weidong Wang,et al.  New Advances in the DNA Damage Response Network of Fanconi Anemia and BRCA proteins: FAAP95 Replaces BRCA2 as the True FANCB Protein , 2005, Cell cycle.

[54]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[55]  F. Autschbach,et al.  Impaired expression of acyl-CoA-synthetase 5 in epithelial tumors of the small intestine. , 2003, Human pathology.

[56]  M. Katoh,et al.  CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. , 2003, International journal of molecular medicine.

[57]  J. Bamburg,et al.  ADF/cofilin and actin dynamics in disease. , 2002, Trends in cell biology.

[58]  A. Theocharis.  Human colon adenocarcinoma is associated with specific post-translational modifications of versican and decorin. , 2002, Biochimica et biophysica acta.

[59]  A. Theocharis,et al.  Compositional and structural alterations of proteoglycans in human rectum carcinoma with special reference to versican and decorin. , 2002, Anticancer research.

[60]  B. Evers,et al.  Downregulation of mitogen-activated protein kinases in human colon cancers. , 2000, Anticancer research.

[61]  C. Spilker,et al.  The Neuronal Calcium‐Sensor Protein VILIP Modulates Cyclic AMP Accumulation in Stably Transfected C6 Glioma Cells: Amino‐Terminal Myristoylation Determines Functional Activity , 1997, Journal of neurochemistry.

[62]  H. Sorimachi,et al.  Calpains: an elaborate proteolytic system. , 2012, Biochimica et biophysica acta.

[63]  M. von Knebel Doeberitz,et al.  Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients. , 2008, International journal of oncology.

[64]  A. Zhu,et al.  Targeting the epidermal growth factor receptor in metastatic colorectal cancer. , 2008, Critical reviews in oncology/hematology.

[65]  P. Laurent-Puig.  [Genetic alterations in colorectal cancer]. , 1994, Annales de pathologie.

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