Plakophilins in Desmosomal Adhesion and Signaling

Figures & data

Figure 1. Sequence conservation of PKPs.

Phylogenetic analysis of the PKPs is based on cDNA-sequences of the respective coding sequences (CDS) or 3´-UTR. The phylogenetic tree was created using the “One click” mode of the Phylogeny.fr platform (Castresana, 2000; Guindon and Gascuel, 2003; Edgar, 2004; Anisimova and Gascuel, 2006; Chevenet et al., 2006; Dereeper et al., 2008; Dereeper et al., 2010). The length of the horizontal connections correlates with the degree of nucleotide substitution.

Figure 2. Regulation and functions of PKPs1–3.

Figure 3. Changes in PKP expression in various tumors.

The NextBio Disease Atlas (Kupershmidt et al., 2010) was used to identify studies showing significantly altered expression of the PKPs in various cancers compared to the corresponding normal tissues. Red bars correspond to the number of studies showing up-regulation, green bars indicate the number of studies showing a down-regulation of PKP-mRNA levels.

Table 1. PKP expression in cancer.

Name of study	PKP1	PKP2	PKP3	References
Intestine
Expression data from colorectal cancer patients	↑	↓	↑	(Sheffer et al., 2009)
Colon cancer tumor and normal biopsies from a series of patients	↔	↔	↑	(Ancona et al., 2006)
Midgut carcinoid primary tumors and liver metastasis expression profiling	↓		↓	(Leja et al., 2009)
Epithelial and stromal tissues in colorectal cancer	↑	↔	↓	(Abba et al., 2012)
Expression profiling in early onset colorectal cancer	↔	↓	↓	(Hong et al., 2007)
Colon biopsies of benign adenomas and malignant adenocarcinomas	↑	↓	↔	GEO accession GSE37364
Colorectal cancer gene expression profiles in tumors and matched adjacent tissue	↔	↓	↔	(Hinoue et al., 2012)
Expression data from human colonic epithelial cells	↑	↓	↔	(Galamb et al., 2010)
Multiclass cancer diagnosis using tumor gene expression signatures	↔	↑	↔	(Ramaswamy et al., 2001)
Colorectal carcinoma regulated gene expression in Middle Eastern patients	↑	↓	↑	(Uddin et al., 2011)
Colon adenocarcinomas and matched normal tissue	↔	↓	↔	(Lin et al., 2006)
Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data	↑	↓	↔	(Skrzypczak et al., 2010)
Expression data from human colonic biopsy sample	↔	↓	↔	(Galamb et al., 2008)
Expression data from normal colon tissues and colon tumors	↔	↓	↔	(Irizarry et al., 2009)
Colon cancer samples compared with adjacent normal colon	↑	↔	↔	(Callari et al., 2012)
Epithelial and stromal tissues in colorectal cancer	↑	↓	↔	(Abba et al., 2012)
Time dependent changes of gene expression in surgical specimen of colorectal cancer	↑	↔	↔	GEO accession GSE50746
Mutated or wildtype KRAS in rectal cancer patients	↓	↑	↔	(Gaedcke et al., 2010)
Stomach
Gastric Cancer Study	↔	↑	↓	(Chen et al., 2003)
Expression data from primary gastric tumors and adjacent normal samples	↓	↑	↑	(D’Errico et al., 2009)
Gastric carcinoma and GIST gene expression profiling	↑	↑	↑	(Cho et al., 2011)
Expression data from gastric cancer	↓	↓	↑	(Peng et al., 2006)
Gastric stromal tumor and non-malignant gastric tissue expression profiles	↔	↔	↑	(Wu et al., 2013)
Bladder
DNA methylation and expression profiling study for bladder cancer	↔	↔	↑	(Kim et al., 2013b)
Comparative Gene Expression Profiling Analysis of Urothelial Carcinoma of Renal Pelvis and Bladder	↑	↑	↑	GEO accession GSE24152
Urethelial carcinoma of bladder	↑	↔	↑	(Zhou et al., 2013)
Clinical bladder cancer classification	↑	↔	↑	(Mengual et al., 2009)
Classification of carcinoma in situ lesions in human bladder cancer	↑	↔	↑	(Dyrskjot et al., 2004)
Multiclass cancer diagnosis using tumor gene expression signature	↑	↑	↔	(Ramaswamy et al., 2001)
Skin
Malignant transformation and progression of metastatic melanoma	↔	↔	↑	(Riker et al., 2008)
Novel Molecular Markers for non-melanoma skin cancer	↑	↔	↑	(Nindl et al., 2006)
Head and Neck
Hypopharyngeal cancer transcriptome	↑	↔	↓	(Cromer et al., 2004)
Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators	↑	↔	↑	(Estilo et al., 2009)
Tongue carcinomas with TNM staging and normal control comparisons	↓	↑	↓	(Rentoft et al., 2012)
Oral Cavity Cancer Compared to Adjacent “Normal” Tissue	↓	↑	↓	(Lohavanichbutr et al., 2013)
Tumor invasion in Oral Squamous Cell Carcinoma	↓	↔	↓	(Toruner et al., 2004)
Expression data from biopsies of Nasopharyngeal carcinoma (NPC) and non-malignant controls	↑	↔	↔	(Bose et al., 2009)
mRNA expression profiling of nasopharyngeal carcinoma	↔	↑	↔	(Dodd et al., 2006; Sengupta et al., 2006)
Gene expression profiling of oral squamous cell carcinoma	↑	↑	↓	(Chen et al., 2008)
Breast
Breast tissue comparative analysis of infiltrating ductal carcinoma	↑	↑	↑	(Hawthorn et al., 2010)
Molecular Signature of Pregnancy Associated Breast Cancer	↓	↑	↔	(Harvell et al., 2013)
Metastatic and primary breast tumors	↔	↓	↔	(Hu et al., 2009)
Human body index - transcriptional profiling	↓	↓	↔	GEO accession GSE7307
Transcription profiling of breast tumors and surrounding tissue	↓	↑	↑	(Cheng et al., 2008)
A gene expression signature identifies two prognostic subgroups of basal breast cancer	↓	↓	↑	(Sabatier et al., 2011; Sircoulomb et al., 2010)
Expression profiling of human DCIS and invasive ductal breast carcinoma	↓	↔	↑	GEO accession GSE21422
Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue	↓	↔	↑	(Chen et al., 2010)
Expression in normal and cancerous breast cell lines and tissues	↓	↔	↑	(Novak et al., 2006)
Gene expression signatures in breast cancer	↓	↑	↑	(Pedraza et al., 2010)
Identifying breast cancer biomarkers	↓	↔	↔	GEO accession GSE29431
Study of Multiple Solid Cancers	↓	↓	↑	(Yu et al., 2008)
Invasive lobular and ductal carcinomas of the breast	↓	↓	↔	(Zhao et al., 2004)
Expression data from human breast tissue	↓	↑	↔	(Richardson et al., 2006)
Early Dysregulation of Cell Adhesion and Extracellular Matrix Pathways in Breast Cancer Progression	↓	↔	↔	(Emery et al., 2009)
Lung
Lung tumors in human and mouse—human subset	↔	↔	↑	(Stearman et al., 2005)
Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas	↔	↑	↑	(Kim et al., 2013a)
Glycine decarboxylase is a metabolic oncogene critical for tumor initiating cells and tumorigenesis in lung cancer	↑	↔	↑	(Zhang et al., 2012)
Lung gene expression of non-smoking female lung cancer	↓	↔	↑	(Lu et al., 2010)
Expression data from Lung cancer	↔	↔	↑	(Su et al., 2007)
Non-Small Cell Lung Cancer	↑	↑	↑	(Dehan et al., 2007)
Expression data for early stage NSCLC	↑	↑	↑	(Hou et al., 2010)
Lung adenocarcinoma stage I, II, and II and healthy lung tissue	↑	↑	↑	GEO accession GSE40791
Gene expression profile of lung tumors	↔	↑	↑	(Wrage et al., 2009)
Study of Multiple Solid Cancers	↔	↔	↑	(Yu et al., 2008)
Lung tumors from 293 patients with clinical outcome	↑	↑	↑	(Rousseaux et al., 2013)
Gene expression analysis of human lung cancer	↑	↑	↑	(Sanchez-Palencia et al., 2011)
Primary lung adenocarcinoma expression profiles	↔	↔	↑	GEO accession GSE31908
Whole-Genome Gene Expression Profiling of Formalin-Fixed, Paraffin-Embedded Tissue Samples	↑	↑	↔	(April et al., 2009)
Classification of High-grade neuroendocrine tumors of the lung	↑	↔	↔	(Jones et al., 2004)
Gene expression data of primary lung cancer	↑	↔	↔	(Moriya et al., 2009)
Squamous Lung Cancer and adjacent normal tissue	↑	↔	↔	(Wachi et al., 2005)
Gene expression data for pathological stage I-II lung adenocarcinomas	↓	↑	↑	(Okayama et al., 2012)
Gene expression profiling of Non-small cell lung cancer	↓	↔	↑	(Wei et al., 2012)
Prostate
Gene expression profiling identifies clinically relevant subtypes of prostate cancer	↓	↓	↑	(Lapointe et al., 2004)
Gene expression down-regulation in prostate tumor-associated stromal cells	↔	↓	↑	(Pascal et al., 2009)
Prostate cancer and normal prostate tissue	↔	↔	↑	GEO accession GSE30522
Expression Data from Normal and Prostate Tumor Tissues	↓	↔	↑	(Chandran et al., 2007; Yu et al., 2004)
Gene expression profiling of prostate cancer	↔	↔	↑	(Arencibia et al., 2009)
Gene signatures in prostate cancer linked to the Gleason score	↓	↔	↑	(Kuner et al., 2013)
Comprehensive gene expression analysis of primary and metastatic prostate cancer	↑	↔	↔	(LaTulippe et al., 2002)
Esophagus
Study of Multiple Solid Cancers	↔	↔	↓	(Yu et al., 2008)
Esophageal epithelium in patients with Barrett’s esophagus or squamous cell carcinoma	↓	↑	↓	GEO accession GSE26886
Esophageal squamous cell carcinoma and normal esophageal tissue expression profiles	↓	↔	↓	(Yan et al., 2012)
Esophageal squamous cell carcinoma gene expression profiling	↔	↔	↓	GSE17351
Esophageal adenocarcinoma and Barrett’s esophagus global gene expression signatures	↓	↑	↓	(Kim et al., 2010)
Gene expression profiling in esophageal squamous cell carcinoma	↔	↔	↓	(Su et al., 2011)
Barrett’s esophagus—metaplasia progression to adenocarcinoma	↓	↑	↓	(Grotenhuis et al., 2010)
Barrett’s esophagus and adenocarcinoma compared to normal esophageal	↓	↑	↓	(Hao et al., 2006)
Barrett’s esophagus—metaplasia progression to adenocarcinoma	↓	↑	↓	(Kimchi et al., 2005)
Psoriasis/Eczema
Gene expression data of skin from psoriatic patients and normal controls	↑	↓	↑	(Nair et al., 2009; Swindell et al., 2011)
Skin lesion gene expression in efalizumab-responsive psoriasis patients	↑	↔	↑	(Johnson-Huang et al., 2012)
Affected and unaffected skin of psoriasis patients and psoriasis free individuals	↑	↔	↑	(Kulski et al., 2005)
Lesional and non-lesional skin from psoriasis patients	↑	↓	↑	(Yao et al., 2008)
Expression data from skin biopsy samples from patients with moderate-to-severe psoriasis	↑	↓	↑	(Suarez-Farinas et al., 2012)
Comparison of Gene Expression in Psoriatic Skin from Different Sources	↑	↓	↑	(Bigler et al., 2013)
Expression data from human skin biposies from psoriatic patients	↑	↔	↑	(Reischl et al., 2007)
Psoriasis-associated gene expression in lesional and non-lesional epidermis and dermis	↑	↔	↑	(Mitsui et al., 2012)
Skin biopsies from atopic eczema and healthy controls	↑	↔	↑	(Olsson et al., 2006)

Summary of studies identified by NextBio Disease Atlas (Kupershmidt et al., 2010) showing significantly altered expression of the PKPs in various tumors compared to the corresponding normal tissue. ↑ mRNA up-regulation; ↓ mRNA down-regulation; ↔ mRNA expression not affected or not determined.

Figure 4. Regulation of PKP1 function by insulin/IGF-1-signaling.

Castresana J (2000). Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol. 17: 540–552.

 PubMed Web of Science ®Google Scholar

Guindon S, Gascuel O (2003). A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 52: 696–704.

 PubMed Web of Science ®Google Scholar

Edgar RC (2004). MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32: 1792–1797.

 PubMed Web of Science ®Google Scholar

Anisimova M, Gascuel O (2006). Approximate likelihood- ratio test for branches: a fast, accurate, and powerful alternative. Syst Biol. 55: 539–552.

 PubMed Web of Science ®Google Scholar

Chevenet F, Brun C, Banuls AL, Jacq B, Christen R (2006). TreeDyn: towards dynamic graphics and annotations for analyses of trees. BMC Bioinformatics. 7: 439.

 PubMed Web of Science ®Google Scholar

Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O (2008). Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 36: W465–469.

 PubMed Web of Science ®Google Scholar

Dereeper A, Audic S, Claverie JM, Blanc G (2010). BLAST-EXPLORER helps you building datasets for phylogenetic analysis. BMC Evol Biol. 10: 8.

 PubMed Web of Science ®Google Scholar

Kupershmidt I, Su QJ, Grewal A, Sundaresh S, Halperin I, Flynn J, Shekar M, Wang H, Park J, Cui W, Wall GD, Wisotzkey R, Alag S, Akhtari S, Ronaghi M (2010). Ontology-based meta-analysis of global collections of high-throughput public data. PLoS One. 5: e10.1371

 Google Scholar

Sheffer M, Bacolod MD, Zuk O, Giardina SF, Pincas H, Barany F, Paty PB, Gerald WL, Notterman DA, Domany E (2009). Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc Natl Acad Sci U S A. 106: 7131–7136.

 PubMed Web of Science ®Google Scholar

Ancona N, Maglietta R, Piepoli A, D'addabbo A, Cotugno R, Savino M, Liuni S, Carella M, Pesole G, Perri F (2006). On the statistical assessment of classifiers using DNA microarray data. BMC Bioinformatics. 7: 387.

 PubMed Web of Science ®Google Scholar

Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH, Lloyd R, Vasmatzis G, Demoulin JB, Giandomenico V (2009). Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol. 22: 261–272.

 Google Scholar

Abba M, Laufs S, Aghajany M, Korn B, Benner A, Allgayer H (2012). Look who's talking: deregulated signaling in colorectal cancer. Cancer Genomics Proteomics. 9: 15–25.

 PubMed Web of Science ®Google Scholar

Hong Y, Ho KS, Eu KW, Cheah PY (2007). A susceptibility gene set for early onset colorectal cancer that integrates diverse signaling pathways: implication for tumorigenesis. Clin Cancer Res. 13: 1107–1114.

 PubMed Web of Science ®Google Scholar

Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, Van Dijk CM, Tollenaar RA, Laird PW (2012). Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 22: 271–282.

 PubMed Web of Science ®Google Scholar

Galamb O, Spisak S, Sipos F, Toth K, Solymosi N, Wichmann B, Krenacs T, Valcz G, Tulassay Z, Molnar B (2010). Reversal of gene expression changes in the colorectal normal- adenoma pathway by NS398 selective COX2 inhibitor. Br J Cancer. 102: 765–773.

 PubMed Web of Science ®Google Scholar

Ramaswamy S, Tamayo P, Rifkin R, Mukherjee S, Yeang CH, Angelo M, Ladd C, Reich M, Latulippe E, Mesirov JP, Poggio T, Gerald W, Loda M, Lander ES, Golub TR (2001). Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci U S A. 98: 15149–15154.

 PubMed Web of Science ®Google Scholar

Uddin S, Ahmed M, Hussain A, Abubaker J, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Jehan Z, Bavi P, Siraj AK, Al-Kuraya KS (2011). Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy. Am J Pathol. 178: 537–547.

 PubMed Web of Science ®Google Scholar

Lin G, He X, Ji H, Shi L, Davis RW, Zhong S (2006). Reproducibility Probability Score–incorporating measurement variability across laboratories for gene selection. Nat Biotechnol. 24: 1476–1477.

 PubMed Web of Science ®Google Scholar

Skrzypczak M, Goryca K, Rubel T, Paziewska A, Mikula M, Jarosz D, Pachlewski J, Oledzki J, Ostrowski J (2010). Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One. 5.

 PubMed Web of Science ®Google Scholar

Galamb O, Sipos F, Solymosi N, Spisak S, Krenacs T, Toth K, Tulassay Z, Molnar B (2008). Diagnostic mRNA expression patterns of inflamed, benign, and malignant colorectal biopsy specimen and their correlation with peripheral blood results. Cancer Epidemiol Biomarkers Prev. 17: 2835–2845.

 PubMed Web of Science ®Google Scholar

Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP (2009). The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 41: 178–186.

 PubMed Web of Science ®Google Scholar

Callari M, Dugo M, Musella V, Marchesi E, Chiorino G, Grand MM, Pierotti MA, Daidone MG, Canevari S, De Cecco L (2012). Comparison of microarray platforms for measuring differential microRNA expression in paired normal/cancer colon tissues. PLoS One. 7: e45105.

 PubMed Web of Science ®Google Scholar

Gaedcke J, Grade M, Jung K, Camps J, Jo P, Emons G, Gehoff A, Sax U, Schirmer M, Becker H, Beissbarth T, Ried T, Ghadimi BM (2010). Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. Genes Chromosomes Cancer. 49: 1024–1034.

 PubMed Web of Science ®Google Scholar

Chen X, Leung SY, Yuen ST, Chu KM, Ji J, Li R, Chan AS, Law S, Troyanskaya OG, Wong J, So S, Botstein D, Brown PO (2003). Variation in gene expression patterns in human gastric cancers. Mol Biol Cell. 14: 3208–3215.

 PubMed Web of Science ®Google Scholar

D’Errico M, De Rinaldis E, Blasi MF, Viti V, Falchetti M, Calcagnile A, Sera F, Saieva C, Ottini L, Palli D, Palombo F, Giuliani A, Dogliotti E (2009). Genome-wide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer. 45: 461–469.

 PubMed Web of Science ®Google Scholar

Cho JY, Lim JY, Cheong JH, Park YY, Yoon SL, Kim SM, Kim SB, Kim H, Hong SW, Park YN, Noh SH, Park ES, Chu IS, Hong WK, Ajani JA, Lee JS (2011). Gene expression signature-based prognostic risk score in gastric cancer. Clin Cancer Res. 17: 1850–1857.

 Google Scholar

Peng Z, Wei D, Wang L, Tang H, Zhang J, Le X, Jia Z, Li Q, Xie K (2006). RUNX3 inhibits the expression of vascular endothelial growth factor and reduces the angiogenesis, growth, and metastasis of human gastric cancer. Clin Cancer Res. 12: 6386–6394.

 PubMed Web of Science ®Google Scholar

Wu Y, Grabsch H, Ivanova T, Tan IB, Murray J, Ooi CH, Wright AI, West NP, Hutchins GG, Wu J, Lee M, Lee J, Koo JH, Yeoh KG, Van Grieken N, Ylstra B, Rha SY, Ajani JA, Cheong JH, Noh SH, Lim KH, Boussioutas A, Lee JS, Tan P (2013). Comprehensive genomic meta- analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer. Gut. 62: 1100–1111.

 PubMed Web of Science ®Google Scholar

Kim YJ, Yoon HY, Kim JS, Kang HW, Min BD, Kim SK, Ha YS, Kim IY, Ryu KH, Lee SC, Kim WJ (2013b). HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: array- based DNA methylation and expression profiling. Int J Cancer. 133: 1135–1142.

 PubMed Web of Science ®Google Scholar

Zhou N, Singh K, Mir MC, Parker Y, Lindner D, Dreicer R, Ecsedy JA, Zhang Z, Teh BT, Almasan A, Hansel DE (2013). The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo. Clin Cancer Res. 19: 1717–1728.

 PubMed Web of Science ®Google Scholar

Mengual L, Burset M, Ars E, Lozano JJ, Villavicencio H, Ribal MJ, Alcaraz A (2009). DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers. J Urol. 182: 741–748.

 Google Scholar

Dyrskjot L, Kruhoffer M, Thykjaer T, Marcussen N, Jensen JL, Moller K, Orntoft TF (2004). Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res. 64: 4040–4048.

 PubMed Web of Science ®Google Scholar

Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B, Samant RS, Shevde LA, Li W, Eschrich S, Daud A, Ju J, Matta J (2008). The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics. 1: 13.

 PubMed Web of Science ®Google Scholar

Nindl I, Dang C, Forschner T, Kuban RJ, Meyer T, Sterry W, Stockfleth E (2006). Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling. Mol Cancer. 5: 30.

 PubMed Web of Science ®Google Scholar

Cromer A, Carles A, Millon R, Ganguli G, Chalmel F, Lemaire F, Young J, Dembele D, Thibault C, Muller D, Poch O, Abecassis J, Wasylyk B (2004). Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis. Oncogene. 23: 2484–2498.

 PubMed Web of Science ®Google Scholar

Estilo CL, O-Charoenrat P, Talbot S, Socci ND, Carlson DL, Ghossein R, Williams T, Yonekawa Y, Ramanathan Y, Boyle JO, Kraus DH, Patel S, Shaha AR, Wong RJ, Huryn JM, Shah JP, Singh B (2009). Oral tongue cancer gene expression profiling: identification of novel potential prognosticators by oligonucleotide microarray analysis. BMC Cancer. 9: 11.

 PubMed Web of Science ®Google Scholar

Rentoft M, Coates PJ, Laurell G, Nylander K (2012). Transcriptional profiling of formalin fixed paraffin embedded tissue: pitfalls and recommendations for identifying biologically relevant changes. PLoS One. 7: e35276.

 PubMedGoogle Scholar

Lohavanichbutr P, Mendez E, Holsinger FC, Rue TC, Zhang Y, Houck J, Upton MP, Futran N, Schwartz SM, Wang P, Chen C (2013). A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation. Clin Cancer Res. 19: 1197–1203.

 PubMed Web of Science ®Google Scholar

Toruner GA, Ulger C, Alkan M, Galante AT, Rinaggio J, Wilk R, Tian B, Soteropoulos P, Hameed MR, Schwalb MN, Dermody JJ (2004). Association between gene expression profile and tumor invasion in oral squamous cell carcinoma. Cancer Genet Cytogenet. 154: 27–35.

 PubMed Web of Science ®Google Scholar

Bose S, Yap LF, Fung M, Starzcynski J, Saleh A, Morgan S, Dawson C, Chukwuma MB, Maina E, Buettner M, Wei W, Arrand J, Lim PV, Young LS, Teo SH, Stankovic T, Woodman CB & Murray PG (2009). The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma. J Pathol. 217: 345–352.

 PubMed Web of Science ®Google Scholar

Dodd LE, Sengupta S, Chen IH, Den Boon JA, Cheng YJ, Westra W, Newton MA, Mittl BF, Mcshane L, Chen CJ, Ahlquist P, Hildesheim A (2006). Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 15: 2216–2225.

 PubMed Web of Science ®Google Scholar

Sengupta S, Den Boon JA, Chen IH, Newton MA, Dahl DB, Chen M, Cheng YJ, Westra WH, Chen CJ, Hildesheim A, Sugden B, Ahlquist P (2006). Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma. Cancer Res. 66: 7999–8006.

 PubMed Web of Science ®Google Scholar

Chen C, Mendez E, Houck J, Fan W, Lohavanichbutr P, Doody D, Yueh B, Futran ND, Upton M, Farwell DG, Schwartz SM, Zhao LP (2008). Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 17: 2152–2162.

 PubMed Web of Science ®Google Scholar

Hawthorn L, Luce J, Stein L, Rothschild J (2010). Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast. BMC Cancer. 10: 460.

 PubMed Web of Science ®Google Scholar

Harvell DM, Kim J, O'brien J, Tan AC, Borges VF, Schedin P, Jacobsen BM, Horwitz KB (2013). Genomic signatures of pregnancy-associated breast cancer epithelia and stroma and their regulation by estrogens and progesterone. Horm Cancer. 4: 140–153.

 PubMedGoogle Scholar

Hu Z, Fan C, Livasy C, He X, Oh DS, Ewend MG, Carey LA, Subramanian S, West R, Ikpatt F, Olopade OI, Van De Rijn M, Perou CM (2009). A compact VEGF signature associated with distant metastases and poor outcomes. BMC Med. 7: 9.

 PubMed Web of Science ®Google Scholar

Cheng AS, Culhane AC, Chan MW, Venkataramu CR, Ehrich M, Nasir A, Rodriguez BA, Liu J, Yan PS, Quackenbush J, Nephew KP, Yeatman TJ, Huang TH (2008). Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome. Cancer Res. 68: 1786–1796.

 PubMed Web of Science ®Google Scholar

Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, Tallet A, Chabannon C, Extra JM, Jacquemier J, Viens P, Birnbaum D, Bertucci F (2011). A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 126: 407–420.

 PubMedGoogle Scholar

Sircoulomb F, Bekhouche I, Finetti P, Adelaide J, Ben Hamida A, Bonansea J, Raynaud S, Innocenti C, Charafe-Jauffret E, Tarpin C, Ben Ayed F, Viens P, Jacquemier J, Bertucci F, Birnbaum D, Chaffanet M (2010). Genome profiling of ERBB2-amplified breast cancers. BMC Cancer. 10: 539.

 PubMedGoogle Scholar

Chen DT, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R, Wang T, Agrawal D, Mccarthy SM, Gruidl M, Bloom G, Anderson T, White J, Quackenbush J, Yeatman T (2010). Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treat. 119: 335–346.

 Google Scholar

Novak P, Jensen T, Oshiro MM, Wozniak RJ, Nouzova M, Watts GS, Klimecki WT, Kim C, Futscher BW (2006). Epigenetic inactivation of the HOXA gene cluster in breast cancer. Cancer Res. 66: 10664–10670.

 PubMed Web of Science ®Google Scholar

Pedraza V, Gomez-Capilla JA, Escaramis G, Gomez C, Torne P, Rivera JM, Gil A, Araque P, Olea N, Estivill X, Farez-Vidal ME (2010). Gene expression signatures in breast cancer distinguish phenotype characteristics, histologic subtypes, and tumor invasiveness. Cancer. 116: 486–496.

 PubMed Web of Science ®Google Scholar

Yu K, Ganesan K, Tan LK, Laban M, Wu J, Zhao XD, Li H, Leung CH, Zhu Y, Wei CL, Hooi SC, Miller L, Tan P (2008). A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers. PLoS Genet. 4: e1000129.

 PubMed Web of Science ®Google Scholar

Zhao H, Langerod A, Ji Y, Nowels KW, Nesland JM, Tibshirani R, Bukholm IK, Karesen R, Botstein D, Borresen-Dale AL, Jeffrey SS (2004). Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol Biol Cell. 15: 2523–2536.

 PubMed Web of Science ®Google Scholar

Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S (2006). X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 9: 121–132.

 PubMed Web of Science ®Google Scholar

Emery LA, Tripathi A, King C, Kavanah M, Mendez J, Stone MD, De Las Morenas A, Sebastiani P, Rosenberg CL (2009). Early dysregulation of cell adhesion and extracellular matrix pathways in breast cancer progression. Am J Pathol. 175: 1292–1302.

 PubMed Web of Science ®Google Scholar

Stearman RS, Dwyer-Nield L, Zerbe L, Blaine SA, Chan Z, Bunn PA, Jr., Johnson GL, Hirsch FR, Merrick DT, Franklin WA, Baron AE, Keith RL, Nemenoff RA, Malkinson AM, Geraci MW (2005). Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model. Am J Pathol. 167: 1763–1775.

 PubMed Web of Science ®Google Scholar

Kim IJ, Quigley D, To MD, Pham P, Lin K, Jo B, Jen KY, Raz D, Kim J, Mao JH, Jablons D, Balmain A (2013a). Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas. Nat Commun. 4: 1701.

 PubMedGoogle Scholar

Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Pang YH, Ang HS, Mitchell W, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B (2012). Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 148: 259–272.

 PubMed Web of Science ®Google Scholar

Lu TP, Tsai MH, Lee JM, Hsu CP, Chen PC, Lin CW, Shih JY, Yang PC, Hsiao CK, Lai LC, Chuang EY (2010). Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women. Cancer Epidemiol Biomarkers Prev. 19: 2590–2597.

 PubMed Web of Science ®Google Scholar

Su LJ, Chang CW, Wu YC, Chen KC, Lin CJ, Liang SC, Lin CH, Whang-Peng J, Hsu SL, Chen CH, Huang CY (2007). Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme. BMC Genomics. 8: 140.

 PubMed Web of Science ®Google Scholar

Dehan E, Ben-Dor A, Liao W, Lipson D, Frimer H, Rienstein S, Simansky D, Krupsky M, Yaron P, Friedman E, Rechavi G, Perlman M, Aviram-Goldring A, Izraeli S, Bittner M, Yakhini Z, Kaminski N (2007). Chromosomal aberrations and gene expression profiles in non-small cell lung cancer. Lung Cancer. 56: 175–184.

 PubMed Web of Science ®Google Scholar

Hou J, Aerts J, Den Hamer B, Van Ijcken W, Den Bakker M, Riegman P, Van Der Leest C, Van Der Spek P, Foekens JA, Hoogsteden HC, Grosveld F, Philipsen S (2010). Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One. 5: e10312.

 PubMed Web of Science ®Google Scholar

Wrage M, Ruosaari S, Eijk PP, Kaifi JT, Hollmen J, Yekebas EF, Izbicki JR, Brakenhoff RH, Streichert T, Riethdorf S, Glatzel M, Ylstra B, Pantel K, Wikman H (2009). Genomic profiles associated with early micrometastasis in lung cancer: relevance of 4q deletion. Clin Cancer Res. 15: 1566–1574.

 PubMed Web of Science ®Google Scholar

Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagy-Mignotte H, Moro-Sibilot D, Brichon PY, Lantuejoul S, Hainaut P, Laffaire J, De Reynies A, Beer DG, Timsit JF, Brambilla C, Brambilla E, Khochbin S (2013). Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med. 5: 186ra66.

 Google Scholar

Sanchez-Palencia A, Gomez-Morales M, Gomez-Capilla JA, Pedraza V, Boyero L, Rosell R, Farez-Vidal ME (2011). Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer. Int J Cancer. 129: 355–364.

 Google Scholar

April C, Klotzle B, Royce T, Wickham-Garcia E, Boyaniwsky T, Izzo J, Cox D, Jones W, Rubio R, Holton K, Matulonis U, Quackenbush J, Fan JB (2009). Whole-genome gene expression profiling of formalin-fixed, paraffin-embedded tissue samples. PLoS One. 4: e8162.

 PubMedGoogle Scholar

Jones MH, Virtanen C, Honjoh D, Miyoshi T, Satoh Y, Okumura S, Nakagawa K, Nomura H, Ishikawa Y (2004). Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. Lancet. 363: 775–781.

 PubMed Web of Science ®Google Scholar

Moriya Y, Iyoda A, Kasai Y, Sugimoto T, Hashida J, Nimura Y, Kato M, Takiguchi M, Fujisawa T, Seki N, Yoshino I (2009). Prediction of lymph node metastasis by gene expression profiling in patients with primary resected lung cancer. Lung Cancer. 64: 86–91.

 PubMed Web of Science ®Google Scholar

Wachi S, Yoneda K, Wu R (2005). Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues. Bioinformatics. 21: 4205–4208.

 PubMed Web of Science ®Google Scholar

Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R, Furuta K, Tsuta K, Shibata T, Yamamoto S, Watanabe S, Sakamoto H, Kumamoto K, Takenoshita S, Gotoh N, Mizuno H, Sarai A, Kawano S, Yamaguchi R, Miyano S, Yokota J (2012). Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 72: 100–111.

 PubMed Web of Science ®Google Scholar

Wei TY, Juan CC, Hisa JY, Su LJ, Lee YC, Chou HY, Chen JM, Wu YC, Chiu SC, Hsu CP, Liu KL, Yu CT (2012). Protein arginine methyltransferase 5 is a potential oncoprotein that upregulates G1 cyclins/cyclin-dependent kinases and the phosphoinositide 3-kinase/AKT signaling cascade. Cancer Sci. 103: 1640–1650.

 PubMed Web of Science ®Google Scholar

Lapointe J, Li C, Higgins JP, Van De Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, Demarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR (2004). Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A. 101: 811–816.

 PubMed Web of Science ®Google Scholar

Pascal LE, Goo YA, Vencio RZ, Page LS, Chambers AA, Liebeskind ES, Takayama TK, True LD, Liu AY (2009). Gene expression down-regulation in CD90 + prostate tumor-associated stromal cells involves potential organ-specific genes. BMC Cancer. 9: 317.

 PubMedGoogle Scholar

Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler M, Liang W, Michalopoulos G, Becich M, Monzon FA (2007). Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer. 7: 64.

 PubMed Web of Science ®Google Scholar

Yu YP, Landsittel D, Jing L, Nelson J, Ren B, Liu L, Mcdonald C, Thomas R, Dhir R, Finkelstein S, Michalopoulos G, Becich M, Luo JH (2004). Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. J Clin Oncol. 22: 2790–2799.

 PubMed Web of Science ®Google Scholar

Arencibia JM, Martin S, Perez-Rodriguez FJ, Bonnin A (2009). Gene expression profiling reveals overexpression of TSPAN13 in prostate cancer. Int J Oncol. 34: 457–463.

 PubMed Web of Science ®Google Scholar

Kuner R, Falth M, Pressinotti NC, Brase JC, Puig SB, Metzger J, Gade S, Schafer G, Bartsch G, Steiner E, Klocker H, Sultmann H (2013). The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer. J Mol Med (Berl). 91: 237–248.

 PubMed Web of Science ®Google Scholar

LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V, Gerald WL (2002). Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res. 62: 4499–4506.

 PubMed Web of Science ®Google Scholar

Yan W, Shih JH, Rodriguez-Canales J, Tangrea MA, Ylaya K, Hipp J, Player A, Hu N, Goldstein AM, Taylor PR, Emmert-Buck MR, Erickson HS (2012). Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma. BMC Res Notes. 5: 73.

 PubMedGoogle Scholar

Kim SM, Park YY, Park ES, Cho JY, Izzo JG, Zhang D, Kim SB, Lee JH, Bhutani MS, Swisher SG, Wu X, Coombes KR, Maru D, Wang KK, Buttar NS, Ajani JA, Lee JS (2010). Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome. PLoS One. 5: e15074.

 PubMedGoogle Scholar

Su H, Hu N, Yang HH, Wang C, Takikita M, Wang QH, Giffen C, Clifford R, Hewitt SM, Shou JZ, Goldstein AM, Lee MP, Taylor PR (2011). Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res. 17: 2955–2966.

 PubMed Web of Science ®Google Scholar

Grotenhuis BA, Van Lanschot JJ, Dinjens WN, Wijnhoven BP (2010). The pathogenesis of Barrett's metaplasia and the progression to esophageal adenocarcinoma. Recent Results Cancer Res. 182: 39–63.

 PubMedGoogle Scholar

Hao Y, Triadafilopoulos G, Sahbaie P, Young HS, Omary MB, Lowe AW (2006). Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma. Gastroenterology. 131: 925–933.

 PubMed Web of Science ®Google Scholar

Kimchi ET, Posner MC, Park JO, Darga TE, Kocherginsky M, Karrison T, Hart J, Smith KD, Mezhir JJ, Weichselbaum RR, Khodarev NN (2005). Progression of Barrett's metaplasia to adenocarcinoma is associated with the suppression of the transcriptional programs of epidermal differentiation. Cancer Res. 65: 3146–3154.

 PubMed Web of Science ®Google Scholar

Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR (2009). Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 41: 199–204.

 PubMed Web of Science ®Google Scholar

Swindell WR, Johnston A, Carbajal S, Han G, Wohn C, Lu J, Xing X, Nair RP, Voorhees JJ, Elder JT, Wang XJ, Sano S, Prens EP, Digiovanni J, Pittelkow MR, Ward NL, Gudjonsson JE (2011). Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis. PLoS One. 6: e18266.

 PubMed Web of Science ®Google Scholar

Johnson-Huang LM, Pensabene CA, Shah KR, Pierson KC, Kikuchi T, Lentini T, Gilleaudeau P, Sullivan-Whalen M, Cueto I, Khatcherian A, Hyder LA, Suarez-Farinas M, Krueger JG, Lowes MA (2012). Post-therapeutic relapse of psoriasis after CD11a blockade is associated with T cells and inflammatory myeloid DCs. PLoS One. 7: e30308.

 PubMed Web of Science ®Google Scholar

Kulski JK, Kenworthy W, Bellgard M, Taplin R, Okamoto K, Oka A, Mabuchi T, Ozawa A, Tamiya G, Inoko H (2005). Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals. J Mol Med (Berl). 83: 964–975.

 PubMed Web of Science ®Google Scholar

Yao Y, Richman L, Morehouse C, De Los Reyes M, Higgs BW, Boutrin A, White B, Coyle A, Krueger J, Kiener PA, Jallal B (2008). Type I interferon: potential therapeutic target for psoriasis?PLoS One. 3: e2737.

 PubMed Web of Science ®Google Scholar

Suarez-Farinas M, Li K, Fuentes-Duculan J, Hayden K, Brodmerkel C, Krueger JG (2012). Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J Invest Dermatol. 132: 2552–2564.

 PubMed Web of Science ®Google Scholar

Bigler J, Rand HA, Kerkof K, Timour M, Russell CB (2013). Cross-study homogeneity of psoriasis gene expression in skin across a large expression range. PLoS One. 8: e52242.

 PubMed Web of Science ®Google Scholar

Reischl J, Schwenke S, Beekman JM, Mrowietz U, Sturzebecher S, Heubach JF (2007). Increased expression of Wnt5a in psoriatic plaques. J Invest Dermatol. 127: 163–169.

 PubMed Web of Science ®Google Scholar

Mitsui H, Suarez-Farinas M, Belkin DA, Levenkova N, Fuentes-Duculan J, Coats I, Fujita H, Krueger JG (2012). Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions. J Invest Dermatol. 132: 1615–1626.

 PubMed Web of Science ®Google Scholar

Olsson M, Broberg A, Jernas M, Carlsson L, Rudemo M, Suurkula M, Svensson PA, Benson M (2006). Increased expression of aquaporin 3 in atopic eczema. Allergy. 61: 1132–1137.

 PubMed Web of Science ®Google Scholar