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PubMed1999

Classification of small cell lung cancer and pulmonary carcinoid by gene expression profiles.

Small cell lung cancer is a common type of lung cancer that is generally classified within the spectrum of neuroendocrine lung neoplasms. Using high-density cDNA arrays, we profiled gene expression of small cell lung cancers and compared these expression profiles to those of normal bronchial epithelial cells and pulmonary carcinoids, which are classified as benign neuroendocrine tumors. We found the overall expression profiles of two small cell lung cancer cell lines, two microdissected tissue samples of primary small cell lung cancer, and cultured bronchial epithelial cells to be relatively similar to one another, with an average Pearson correlation coefficient for these comparisons of 0.63. However, we found the expression profiles of small cell lung cancers (and bronchial epithelial cells) to be surprisingly dissimilar to those of two samples of pulmonary carcinoid tumors, with an average correlation coefficient for these comparisons of 0.20. We then compared the pulmonary carcinoid expression profiles to those of two samples of infiltrating astrocytic brain cancers (oligodendroglioma and high-grade astrocytoma) and found similarity of gene expression among these four samples (average correlation coefficient, 0.57). These gene expression profiles suggest that small cell lung cancers are closely related to (and possibly derived from) epithelial cells, and that pulmonary carcinoids are related to neural crest-derived brain tumors. More generally, our results suggest that broad profiles of gene expression may reveal similarities and differences between tumors that are not apparent by traditional morphological criteria.

Carcinoid Tumor↗

PubMed2006

Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma.

BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.

Adenocarcinoma↗

PubMed2006

An improved distance measure between the expression profiles linking co-expression and co-regulation in mouse.

BACKGROUND: Many statistical algorithms combine microarray expression data and genome sequence data to identify transcription factor binding motifs in the low eukaryotic genomes. Finding cis-regulatory elements in higher eukaryote genomes, however, remains a challenge, as searching in the promoter regions of genes with similar expression patterns often fails. The difficulty is partially attributable to the poor performance of the similarity measures for comparing expression profiles. The widely accepted measures are inadequate for distinguishing genes transcribed from distinct regulatory mechanisms in the complicated genomes of higher eukaryotes. RESULTS: By defining the regulatory similarity between a gene pair as the number of common known transcription factor binding motifs in the promoter regions, we compared the performance of several expression distance measures on seven mouse expression data sets. We propose a new distance measure that accounts for both the linear trends and fold-changes of expression across the samples. CONCLUSION: The study reveals that the proposed distance measure for comparing expression profiles enables us to identify genes with large number of common regulatory elements because it reflects the inherent regulatory information better than widely accepted distance measures such as the Pearson's correlation or cosine correlation with or without log transformation.

Algorithms↗

PubMed2002

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor alpha.

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERalpha or mutant(351)ERalpha. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10(-9) or 10(-8) M oestradiol; with 10(-6) M 4-hydroxytamoxifen; with 10(-6) M raloxifene; with 10(-6) M idoxifene, with 10(-6) M EM 652, with 10(-6) M GW 7604; with 5 x 10(-5) M resveratrol and with 10(-6) M ICI 182,780. We developed a new algorithm 'Expression Signatures' to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERalpha and clustered together with EM 652 for cells expressing mutant(351)ERalpha. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions.

Breast Neoplasms↗

PubMed1999

Expression profiling by iAFLP: A PCR-based method for genome-wide gene expression profiling.

The availability of comprehensive sets of genes has prompted the researchers to carry out systematic collection of gene expression data. RT-PCR has the highest specificity and sensitivity for transcript detection among all available methods. Low throughput, especially when quantitative data are desired, has precluded RT-PCR from genome-wide application. Here we report a PCR-based expression profiling method, introduced amplified fragment length polymorphism (iAFLP), that has the same specificity and sensitivity as RT-PCR and a throughput level comparable to that of DNA-microarray hybridization. In this method, restricted ends of total cDNAs from six sources were ligated with adaptors having various length of short insertions to a common sequence (polymorphic adaptors). Amplification of a pool of these differentially adapted cDNAs with a gene-specific primer and an adaptor primer allows us to quantitate the abundance of any transcript in six mRNA sources. Using three different primer colors this technique allows quantitation of expression of 864 genes across six different sources per day with a single autosequencer, which is comparable to the throughput of microarray analysis in terms of number of genes x number of sources.

Animals↗

PubMed2006

[Percentage of neoplastic cells in papillary thyroid carcinoma: implications for DNA microarray studies of gene expression profile].

Studies of gene expression profile using DNA microarray technology are usually performed using either tumor-derived sample material or isolated neoplastic cells obtained through microdissection. The scope of information about neoplastic transformation gained from studying profile of gene expression in microdissected samples would be much wider but collection of sufficient amounts of intact RNA is very difficult. A compromise could be reached by relating gene expression profile to percentage of neoplastic cells in the investigated tissue sample. The ratio of neoplastic cells in the investigated sample of papillary thyroid cancer was assessed through evaluation of approximated count of cell number in 10-18 examined image fields. This information was related to gene expression profiles obtained from DNA microarrays. The study involved 40 cases of papillary thyroid cancer; the percentage of PTC cells varied between 20 and 95% and only in half of the cases exceeded 75%. Correct differentiation of tumor and normal sample by means of gene expression profile was possible only when the percentage of tumor cells exceeded 25-30%. Seventeen genes showing the best correlation with the tumor cell numbers were selected and their classification potential was evaluated. Strength of information derived from gene expression profile studies by DNA microarrays in papillary thyroid cancer cells is very reliable and permits distinguishing correctly between normal and neoplastic tissues even when the percentage of cancer cells does not exceed 25-50%. However, the differentiation potential of gene expression profile is not markedly improved by selection of genes showing best correlation with the number of tumor cells.

Adolescent↗

PubMed2003

Expression profiling and subtype-specific expression of stomach cancer.

The expression profiling and molecular grouping of stomach cancers has been a challenging task because of their complexity and variation. We have analyzed gene expression profiles of 22 gastric cancer/nontumor mucosa couples using 14K cDNA microarray chips designed for gastric cancer analysis. Upon pairwise analysis of the individual couples at the false significance rate 0.91%, 79 and 398 genes were reported to be up-regulated and down-regulated in tumors, respectively. Tumors were clustered into two groups having high and low inflammatory infiltration, respectively. The latter consisted of three subgroups, including diffuse type carcinomas and intestinal types with distinct pathological characteristics of aggressive behavior. When the pooled tumor was hybridized against the pooled nontumor mucosa samples, more genes were detected to express differentially than those detected by the pairwise analysis at the same threshold level. However, they did not render satisfactory clustering of individual tumors. Our data showed that stomach cancers could be clustered effectively using stomach-specific microarrays and pairwise analysis of tumor/nontumor mucosa couples. It is suggested that the application of specific goal-oriented experimental designing would be advantageous for efficient analysis of expression profiles of such a complex disease as gastric cancer.

Adult↗

PubMed2003

Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent.

In order to expand our understanding of the molecular changes underlying the complex pathology of pancreatic malignancy, global gene expression profiling of pancreatic adenocarcinoma compared with normal pancreatic tissue was performed. Human cDNA arrays comprising 9932 elements were interrogated with fluorescence-labelled normal and adenocarcinoma samples (nine tumours, three normal pancreata, and three cell lines). The data were analysed for differential gene expression, which was confirmed by serial analysis of gene expression (SAGE), digital differential display (DDD) analysis, and immunohistochemistry for selected cases. The array data were filtered to produce lists of a total of 75 genes significantly up-regulated or down-regulated in pancreatic adenocarcinoma. Two of those showing the highest differential were members of the S100 family of Ca-binding proteins, namely S100P and S100A6, and therefore the S100 genes were studied in more detail. By immunohistochemical analysis of custom-built, pancreas-specific tissue arrays and commercially available, normal/cancer tissue arrays that included a wide variety of different tumour types, differential expression of S100P protein was found to be almost exclusive to pancreatic cancer. S100P could therefore represent a useful biomarker for pancreatic adenocarcinomas.

Adenocarcinoma↗

PubMed2002

Gene expression profiling in silico: relative expression of candidate angiogenesis associated genes in renal cell carcinomas.

Recent advances in gene expression profiling have led to the development of comprehensive databases which can be queried in various manners. In the present report, we have taken a list of genes previously associated with angiogenesis, either in in vivo or in in vitro models, and queried a commercial database established by GeneLogic to determine the relative expression of these candidate genes in normal kidneys and in renal cell carcinomas (RCC). We identified a number of genes, including CXCR4, matrix metalloproteinase 9, thrombospondin 2, and vascular endothelial growth factor, that were highly expressed in RCC versus normal tissue. One gene, hevin, appears to be selectively upregulated in RCC in contrast to downregulation of this gene in lung and colon tumors. This approach provides a powerful means to identify potential markers of tumor vascularization.

Carcinoma, Renal Cell↗

PubMed2004

Analysis of Bothrops jararacussu venomous gland transcriptome focusing on structural and functional aspects: I--gene expression profile of highly expressed phospholipases A2.

Snake venom glands are a rich source of bioactive molecules such as peptides, proteins and enzymes that show important pharmacological activity leading to in local and systemic effects as pain, edema, bleeding and muscle necrosis. Most studies on pharmacologically active peptides and proteins from snake venoms have been concerned with isolation and structure elucidation through methods of classical biochemistry. As an attempt to examine the transcripts expressed in the venom gland of Bothrops jararacussu and to unveil the toxicological and pharmacological potential of its products at the molecular level, we generated 549 expressed sequence tags (ESTs) from a directional cDNA library. Sequences obtained from single-pass sequencing of randomly selected cDNA clones could be identified by similarities searches on existing databases, resulting in 197 sequences with significant similarity to phospholipase A(2) (PLA(2)), of which 83.2% were Lys49-PLA(2) homologs (BOJU-I), 0.1% were basic Asp49-PLA(2)s (BOJU-II) and 0.6% were acidic Asp49-PLA(2)s (BOJU-III). Adjoining this very abundant class of proteins we found 88 transcripts codifying for putative sequences of metalloproteases, which after clustering and assembling resulted in three full-length sequences: BOJUMET-I, BOJUMET-II and BOJUMET-III; as well as 25 transcripts related to C-type lectin like protein including a full-length cDNA of a putative galactose binding C-type lectin and a cluster of eight serine-proteases transcripts including a full-length cDNA of a putative serine protease. Among the full-length sequenced clones we identified a nerve growth factor (Bj-NGF) with 92% identity with a human NGF (NGHUBM) and an acidic phospholipase A(2) (BthA-I-PLA(2)) displaying 85-93% identity with other snake venom toxins. Genetic distance among PLA(2)s from Bothrops species were evaluated by phylogenetic analysis. Furthermore, analysis of full-length putative Lys49-PLA(2) through molecular modeling showed conserved structural domains, allowing the characterization of those proteins as group II PLA(2)s. The constructed cDNA library provides molecular clones harboring sequences that can be used to probe directly the genetic material from gland venom of other snake species. Expression of complete cDNAs or their modified derivatives will be useful for elucidation of the structure-function relationships of these toxins and peptides of biotechnological interest.

Amino Acid Sequence↗

PubMed2005

Chemostat culture characterization of Escherichia coli mutant strains metabolically engineered for aerobic succinate production: a study of the modified metabolic network based on metabolite profile, enzyme activity, and gene expression profile.

Various Escherichia coli mutant strains designed for succinate production under aerobic conditions were characterized in chemostat. The metabolite profiles, enzyme activities, and gene expression profiles were studied to better understand the metabolic network operating in these mutant strains. The most efficient succinate producing mutant strain HL27659k was able to achieve a succinate yield of 0.91 mol/mol glucose at a dilution rate of 0.1/h. This strain has the five following mutations: sdhAB, (ackA-pta), poxB, iclR, and ptsG. Four other strains involved in this study were HL2765k, HL276k, HL2761k, and HL51276k. Strain HL2765k has mutations in sdhAB, (ackA-pta), poxB and iclR, strain HL276k has mutations in sdhAB, (ackA-pta) and poxB, strain HL2761k has mutations in sdhAB, (ackA-pta), poxB and icd, and strain HL51276k has mutations in iclR, icd, sdhAB, (ackA-pta) and poxB. Enzyme activity data showed strain HL27659k has substantially higher citrate synthase and malate dehydrogenase activities than the other four strains. The data also showed that only iclR mutation strains exhibited isocitrate lyase and malate synthase activities. Gene expression profiles also complemented the studies of enzyme activity and metabolites from chemostat cultures. The results showed that the succinate synthesis pathways engineered in strain HL27659k were highly efficient, yielding succinate as the only major product produced under aerobic conditions. Strain HL27659k was the only strain without pyruvate accumulation, and its acetate production was the least among all the mutant strains examined.

Aerobiosis↗

PubMed2004

Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Biomarkers, Tumor↗

PubMed2003

Gene expression profiling in ataxin-3 expressing cell lines reveals distinct effects of normal and mutant ataxin-3.

Spinocerebellar ataxia type 3 (SCA3) is a late-onset neurodegenerative disorder caused by the expansion of a polyglutamine tract within the gene product, ataxin-3. We have previously shown that mutant ataxin-3 causes upregulation of inflammatory genes in transgenic SCA3 cell lines and human SCA3 pontine neurons. We report here a complex pattern of transcriptional changes by microarray gene expression profiling and Northern blot analysis in a SCA3 cell model. Twenty-three differentially expressed genes involved in inflammatory reactions, nuclear transcription, and cell surface-associated processes were identified. The identified corresponding proteins were analyzed by immunohistochemistry in human disease and control brain tissue to evaluate their implication in SCA3 pathogenesis. In addition to several inflammatory mediators upregulated in mutant ataxin-3 expressing cell lines and pontine neurons of SCA3 patients, we identified a profound repression of genes encoding cell surface-associated proteins in cells overexpressing normal ataxin-3. Correspondingly, these genes were upregulated in mutant ataxin-3 expressing cell lines and in pontine neurons of SCA3 patients. These findings identify for the first time target genes transcriptionally regulated by normal ataxin-3 and support the hypothesis that both loss of normal ataxin-3 and gain of function through protein-protein interacting properties of mutant ataxin-3 contribute to SCA3 pathogenesis.

Animals↗

PubMed2002

Comparison of RNA expression profiles based on maize expressed sequence tag frequency analysis and micro-array hybridization.

Assembly of 73,000 expressed sequence tags (ESTs) representing multiple organs and developmental stages of maize (Zea mays) identified approximately 22,000 tentative unique genes (TUGs) at the criterion of 95% identity. Based on sequence similarity, overlap between any two of nine libraries with more than 3,000 ESTs ranged from 4% to 20% of the constituent TUGs. The most abundant ESTs were recovered from only one or a minority of the libraries, and only 26 EST contigs had members from all nine EST sets (presumably representing ubiquitously expressed genes). For several examples, ESTs for different members of gene families were detected in distinct organs. To study this further, two types of micro-array slides were fabricated, one containing 5,534 ESTs from 10- to 14-d-old endosperm, and the other 4,844 ESTs from immature ear, estimated to represent about 2,800 and 2,500 unique genes, respectively. Each array type was hybridized with fluorescent cDNA targets prepared from endosperm and immature ear poly(A(+)) RNA. Although the 10- to 14-d-old postpollination endosperm TUGs showed only 12% overlap with immature ear TUGs, endosperm target hybridized with 94% of the ear TUGs, and ear target hybridized with 57% of the endosperm TUGs. Incomplete EST sampling of low-abundance transcripts contributes to an underestimate of shared gene expression profiles. Reassembly of ESTs at the criterion of 90% identity suggests how cross hybridization among gene family members can overestimate the overlap in genes expressed in micro-array hybridization experiments.

Contig Mapping↗

PubMed2002

Temporal expression profile of late gene expression factor 4 from Bombyx mori nucleopolyhedrovirus.

Temporal expression profile of lef4, the gene encoding late gene expression factor 4 (LEF4) from the baculovirus, Bombyx mori nucleopolyhedrovirus (BmNPV), has been analysed. lef4 behaved like an early gene and the transcripts were detectable from 6 h post infection (hpi) which reached maximal levels by 18-24 hpi, and declined considerably at later times. The LEF4 open reading frame was bacterially expressed as a glutathione S-transferase (GST) fusion protein which was solubilized from the inclusion bodies and purified by adsorption to the affinity matrix, GST-Sepharose. Using polyclonal antibodies raised against the bacterially expressed protein, the temporal profile of LEF4 synthesis in BmNPV-infected BmN cells was analysed. The LEF4 protein levels were also higher at 24 hpi compared to 12 or 36 hpi, correlating with the RNA patterns. The protein was predominantly localized to the nucleus of the infected BmN cell and only a small portion was present in the cytosolic fraction. Preliminary studies with antisense lef4 expression revealed substantial reduction in expression from the viral polyhedrin promoter without significantly affecting the viral DNA replication.

Animals↗

PubMed2005

cDNA expression profiling reveals elevated gene expression in cell clusters overlying focally disrupted myoepithelial cell layers: implications for breast tumor invasion.

BACKGROUND: Our previous studies revealed that a subset of mammary ductal carcinoma in situ (DCIS) contained focally disrupted myoepithelial (ME) cell layers that were predominantly overlain by estrogen receptor (ER) negative cells, which showed a substantially higher rate of cell proliferation and genetic alterations than adjacent ER positive cells within the same duct. This study attempted to assess whether these cells also had a different expression profile on tumor progression related genes. DESIGN: Consecutive sections were made from frozen tissues of 30 DCIS with focally disrupted ME cell layers and associated ER negative cell clusters. ER negative and adjacent ER positive cells within the same duct were microdissected for RNA extraction and amplification. Amplified RNA was converted to biotin-labeled cDNAs and interrogated with 'Cancer PathwayFinder' arrays. RESULTS: Cells within each or among ER negative clusters were immunohistochemically and morphologically similar, whereas they differed substantially from adjacent cells within the same duct. Of 20-paired informative ER negative and positive cells, 15 genes were differentially expressed. Of which, 11(73.3%) were higher in ER negative, 2 (13.3%) were higher in ER positive, and 2 (13.3%) were equal in these cells (p <0.01). Of 11 up-regulated genes in ER negative cells, 8 indirectly or directly promote proliferation and progression, and 3 promote apoptosis. CONCLUSION: ER negative cell clusters showed a significantly higher expressing frequency of multiple tumor progression related genes than their adjacent ER positive counterparts, suggesting that they are likely to be biologically more aggressive and have a greater potential for invasion.

Breast Neoplasms↗

PubMed2002

Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals.

BACKGROUND: Expression profiling holds great promise for rapid host genome functional analysis. It is plausible that host expression profiling in an infection could serve as a universal phenotype in virally infected cells. Here, we describe the effect of one of the most critical viral activators, Tat, in HIV-1 infected and Tat expressing cells. We utilized microarray analysis from uninfected, latently HIV-1 infected cells, as well as cells that express Tat, to decipher some of the cellular changes associated with this viral activator. RESULTS: Utilizing uninfected, HIV-1 latently infected cells, and Tat expressing cells, we observed that most of the cellular host genes in Tat expressing cells were down-regulated. The down-regulation in Tat expressing cells is most apparent on cellular receptors that have intrinsic receptor tyrosine kinase (RTK) activity and signal transduction members that mediate RTK function, including Ras-Raf-MEK pathway. Co-activators of transcription, such as p300/CBP and SRC-1, which mediate gene expression related to hormone receptor genes, were also found to be down-regulated. Down-regulation of receptors may allow latent HIV-1 infected cells to either hide from the immune system or avoid extracellular differentiation signals. Some of the genes that were up-regulated included co-receptors for HIV-1 entry, translation machinery, and cell cycle regulatory proteins. CONCLUSIONS: We have demonstrated, through a microarray approach, that HIV-1 Tat is able to regulate many cellular genes that are involved in cell signaling, translation and ultimately control the host proliferative and differentiation signals.

Cell Cycle↗

PubMed2006

Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples.

AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens. METHODS: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results. RESULTS: RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique. CONCLUSION: Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

Acute-Phase Proteins↗