Differential gene expression of the key signalling pathway in para‐carcinoma, carcinoma and relapse human pancreatic cancer

Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para‐carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak–STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress. Copyright © 2013 John Wiley & Sons, Ltd.

[1]  M. Hollingsworth,et al.  Molecular pathology of early pancreatic cancer. , 2010, Cancer biomarkers : section A of Disease markers.

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

[3]  S. Choi,et al.  Gene Expression Profiles in Gallbladder Cancer: The Close Genetic Similarity Seen for Early and Advanced Gallbladder Cancers May Explain the Poor Prognosis , 2008, Tumor Biology.

[4]  M. Loh,et al.  Interleukin-10 gene promoter polymorphisms and risk of gastric cancer in a Chinese population: single nucleotide and haplotype analyses. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[5]  F. Jasmine,et al.  Do placental genes affect maternal breast cancer? Association between offspring's CGB5 and CSH1 gene variants and maternal breast cancer risk. , 2008, Cancer research.

[6]  R. López-López,et al.  Molecular markers of endometrial carcinoma detected in uterine aspirates , 2011, International journal of cancer.

[7]  R. Eisenberg,et al.  Protein inhibitor of activated STAT3 expression in lung cancer , 2011, Molecular oncology.

[8]  L. V. van't Veer,et al.  Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  L. Chuang,et al.  Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B. , 2001, Genomics.

[10]  S. Klein,et al.  Common Haplotypes at the Adiponectin Receptor 1 (ADIPOR1) Locus Are Associated With Increased Risk of Coronary Artery Disease in Type 2 Diabetes , 2006, Diabetes.

[11]  T. Valle,et al.  Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study , 2006, Diabetologia.

[12]  M. Hebrok,et al.  KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma , 2010, Nature Reviews Cancer.

[13]  S. Corbett,et al.  Confirmation of a potential biomarker for early-stage pancreatic cancer. , 2011, Cancer biomarkers : section A of Disease markers.

[14]  Maryam H. Al-Zahrani,et al.  The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer. , 2012, Oncology letters.

[15]  M. S. Weedon-Fekjær,et al.  Long-chain polyunsaturated fatty acids stimulate cellular fatty acid uptake in human placental choriocarcinoma (BeWo) cells. , 2009, Placenta.

[16]  Philippe Froguel,et al.  Cloning of adiponectin receptors that mediate antidiabetic metabolic effects , 2003, Nature.

[17]  Wei Gao,et al.  Bioinformatics Method to Analyze the Mechanism of Pancreatic Cancer Disorder , 2013, J. Comput. Biol..

[18]  A. Younes,et al.  Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib , 2013, Expert opinion on investigational drugs.

[19]  M. Lauth,et al.  Hedgehog signaling and pancreatic tumor development. , 2011, Advances in cancer research.

[20]  Yusuke Nakamura,et al.  Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection , 2004, Oncogene.

[21]  G. Watkins,et al.  Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer , 2005, International seminars in surgical oncology : ISSO.

[22]  I. Wistuba,et al.  STAT5A-Mediated SOCS2 Expression Regulates Jak2 and STAT3 Activity Following c-Src Inhibition in Head and Neck Squamous Carcinoma , 2011, Clinical Cancer Research.

[23]  B. Bao,et al.  Activated K-ras and INK4a/Arf Deficiency Cooperate During the Development of Pancreatic Cancer by Activation of Notch and NF-κB Signaling Pathways , 2011, PloS one.

[24]  R. Bronson,et al.  Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. , 2008, Cancer research.

[25]  H. Ostrer,et al.  Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. , 2008, Cancer research.

[26]  C. Mantzoros,et al.  Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. , 2008, JAMA.

[27]  Xiaoying Shen,et al.  Analysis of whole genomic expression profiles and screening of the key signaling pathways associated with pancreatic cancer. , 2012, International journal of clinical and experimental pathology.

[28]  Y. Bang,et al.  OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. , 2013, Cancer letters.

[29]  A. Imai,et al.  Frequent promoter hypermethylation of tachykinin-1 and tachykinin receptor type 1 is a potential biomarker for head and neck cancer , 2013, Journal of Cancer Research and Clinical Oncology.

[30]  Q. Su,et al.  Isolation and bioinformatics analysis of differentially methylated genomic fragments in human gastric cancer. , 2008, World journal of gastroenterology.

[31]  O. Stoeltzing,et al.  STAT5b as molecular target in pancreatic cancer--inhibition of tumor growth, angiogenesis, and metastases. , 2012, Neoplasia.

[32]  Wei-Hong Chen,et al.  Expression of SOCSs in human prostate cancer and their association in prognosis , 2013, Molecular and Cellular Biochemistry.

[33]  D. Hu,et al.  ADIPOQ gene polymorphisms and cancer risk: a meta-analysis. , 2013, Cytokine.

[34]  Elise C. Kohn,et al.  The microenvironment of the tumour–host interface , 2001, Nature.

[35]  R. Simmen,et al.  Cytosolic Malic Enzyme 1 (ME1) Mediates High Fat Diet-Induced Adiposity, Endocrine Profile, and Gastrointestinal Tract Proliferation-Associated Biomarkers in Male Mice , 2012, PloS one.

[36]  S. Esseghir,et al.  Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts , 2006, The Journal of pathology.

[37]  Yushui Ma,et al.  Differential gene expression of Wnt signaling pathway in benign, premalignant, and malignant human breast epithelial cells , 2012, Tumor Biology.

[38]  F. Kronenberg,et al.  Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. , 2006, Diabetes.

[39]  E. Raymond,et al.  Markers involved in resistance to cytotoxics and targeted therapeutics in pancreatic cancer. , 2009, Cancer treatment reviews.

[40]  G. Hostetter,et al.  Identification of novel pancreatic adenocarcinoma cell-surface targets by gene expression profiling and tissue microarray. , 2010, Biochemical pharmacology.

[41]  Joseph O. Moore,et al.  CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant. , 2008, Leukemia research.

[42]  D. Viskochil,et al.  SPRED 1 Mutations in a Neurofibromatosis Clinic , 2010, Journal of child neurology.

[43]  F. Révillion,et al.  Favorable prognostic value of SOCS2 and IGF-I in breast cancer , 2007, BMC Cancer.

[44]  B. Leiby,et al.  Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy. , 2013, Human pathology.

[45]  B. Haimovich,et al.  Alpha-actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction. , 2007, American journal of physiology. Cell physiology.

[46]  Lesley A. Mathews,et al.  Epigenetic Regulation of SOX9 by the NF‐κB Signaling Pathway in Pancreatic Cancer Stem Cells , 2013, Stem cells.

[47]  Guohua Wu,et al.  Whole Genome Expression Profiling Reveals a Significant Role for the Cell Junction and Apoptosis Pathways in Breast Cancer Stem Cells , 2010, Molecular biotechnology.

[48]  Nengjun Yi,et al.  Polymorphisms of ADIPOQ and ADIPOR1 and prostate cancer risk. , 2011, Metabolism: clinical and experimental.

[49]  Chih-Jen Chang,et al.  Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly. , 2007, The American journal of clinical nutrition.

[50]  J. Torchia,et al.  β-Estradiol-dependent activation of the JAK/STAT pathway requires p/CIP and CARM1. , 2013, Biochimica et biophysica acta.

[51]  S. Batra,et al.  Mucin-based targeted pancreatic cancer therapy. , 2012, Current pharmaceutical design.

[52]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[53]  M. Birtwistle,et al.  Novel Somatic Mutations to PI3K Pathway Genes in Metastatic Melanoma , 2012, PloS one.

[54]  Taosheng Chen,et al.  Carnitine palmitoyltransferase 1A (CPT1A): a transcriptional target of PAX3-FKHR and mediates PAX3-FKHR–dependent motility in alveolar rhabdomyosarcoma cells , 2011, BMC Cancer.

[55]  F. Carey,et al.  Novel multiplex method to assess insulin, leptin and adiponectin regulation of inflammatory cytokines associated with colon cancer , 2011, Molecular Biology Reports.

[56]  Y. Miki,et al.  Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome‐wide expression profiling , 2010, Cancer science.

[57]  Z. Nie,et al.  Effects of genetic variations in the Adiponectin pathway genes on the risk of colorectal cancer in the Chinese population , 2011, BMC Medical Genetics.

[58]  S. Mustjoki,et al.  Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. , 2013, Blood.

[59]  B. Fridley,et al.  Inflammation-Related Gene Variants as Risk Factors for Pancreatic Cancer , 2011, Cancer Epidemiology, Biomarkers & Prevention.