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Significant gene expression differences in histologically "Normal" liver biopsies: Implications for control tissue.

ABSTRACT: UNLABELLED: Gene expression technologies allow the analysis of gene networks whose expression is associated with specific pathological conditions compared with normal tissue. We hypothesized that histologically normal tissue obtained in different ways (percutaneous or surgical liver biopsies), usually used as normal controls in gene expression studies, could have different gene expression patterns. Group A comprised percutaneous liver biopsies in 14 patients with mildly elevated alanine aminotransferase in whom all causes of liver disease had been ruled out. Group B comprised 14 surgical liver biopsies of nontumoral livers. All 28 specimens were histologically normal. Real-time quantitative reverse-transcription polymerase chain reaction were used to compare the messenger RNA expression of 240 selected genes in these two groups. Expression of 26 of the 240 genes was significantly different between groups A and B; 23 genes were up-regulated in group A, while three were down-regulated in group B. The most notable changes occurred in the inflammatory response family genes. Eight genes discriminated perfectly between groups A and B: seven up-regulated genes (PAI1, THBS1, IL8, PTGS2, CXCR4, JUN, and FOS), and one down-regulated gene (IHH). In chronic hepatitis C liver samples, a lower or higher expression of a IL8 was found depending on whether the controls were obtained percutaneously or surgically. CONCLUSION: Our study demonstrates that histologically normal liver tissue obtained in two different ways (percutaneous or surgical) has different gene expression patterns emphasizing the importance of an adequate selection of histologically normal controls to prevent discordant results in gene expression studies.

SUBMITTER: Asselah T

PROVIDER: S-EPMC2816363 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Significant gene expression differences in histologically "Normal" liver biopsies: Implications for control tissue.

Asselah Tarik T Bièche Ivan I Laurendeau Ingrid I Martinot-Peignoux Michelle M Paradis Valerie V Vidaud Dominique D Valla Dominique-Charles DC Bedossa Pierre P Marcellin Patrick P Vidaud Michel M

Hepatology (Baltimore, Md.) 20080901 3

<h4>Unlabelled</h4>Gene expression technologies allow the analysis of gene networks whose expression is associated with specific pathological conditions compared with normal tissue. We hypothesized that histologically normal tissue obtained in different ways (percutaneous or surgical liver biopsies), usually used as normal controls in gene expression studies, could have different gene expression patterns. Group A comprised percutaneous liver biopsies in 14 patients with mildly elevated alanine a ...[more]

PMID: 18726958

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Project description:To identify differences in gene expression profiles of infected cells between thyroid carcinoma (C), thyroid adenoma (A) and normal thyroid (N) epithelial cells, differentially expressed genes were identified using three pairwise comparisons with the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to classify them at the functional level. The most significant cluster in the N vs. A pairwise comparison had four hub genes: Insulin-like growth factor 2, Von Willebrand factor (VWF), multimerin 1 (MMRN1) and complement factor D (CFD). In N vs. C, the most significant cluster had 19 genes: IGF2, early growth response 2, transcription factor 3, KIT proto?oncogene receptor tyrosine kinase, SMAD family member 9, MLLT3 super elongation complex subunit, runt related transcription factor 1, CFD, actinin ? 1, SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily a member 4, JunD proto?oncogene AP?1 transcription factor subunit, serum response factor (SRF), FosB proto?oncogene, AP?1 transcription factor subunit, connective tissue growth factor (CTGF), SRC proto?oncogene, non?receptor tyrosine kinase, MMRN1, SRY?box 9, early growth response 3 and ETS variant 4. In A vs. C, the most significant cluster had 14 genes: BCL2-like 1, galectin 3, MCL1 BCL2 family apoptosis regulator, DNA damage inducible transcript 3, BCL2 apoptosis regulator, CTGF, matrix metallopeptidase 7, early growth response 1, kinase insert domain receptor, TIMP metallopeptidase inhibitor 1, apolipoprotein E, VWF, cyclin D1 and placental growth factor. Histological evidence was presented to confirm the makeup of the hubs prior to logistic regression analysis to differentiate benign and malignant neoplasms. The results of the present study may aid in the search for novel potential biomarkers for the differential diagnosis, prognosis and development of drug targets of thyroid neoplasm.

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Significant gene expression differences in histologically "Normal" liver biopsies: Implications for control tissue.

Publications

Significant gene expression differences in histologically "Normal" liver biopsies: Implications for control tissue.

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