Unknown,Transcriptomics,Genomics,Proteomics

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The miRNAome of O. viverrini induced cholangiocarcinoma by microarray:

ABSTRACT: Cholangiocarcinoma is the second most common primary hepatic malignancy worldwide, with intrahepatic cholangiocarcinoma (ICC) a particularly significant public health problem in Southeast Asia, due to its strong association with the food-borne parasite Opisthorchis viverrini (OV). This manuscript represents the first comprehensive miRNA expression profiling by microarray of the three most common histological grades of OV-induced ICC: moderately differentiated, papillary, and well differentiated tumor tissue. No cohort of miRNAs emerged as commonly dysregulated among these histological grades of OV-induced ICC. Instead, each histological grade of ICC tissue showed a distinct miRNA profile. Moderately differentiated tumor tissue showed both the greatest number and the highest magnitude of miRNA dysregulation, followed by papillary ICC tumor tissue, and differentiated ICC tumor tissue. When ICC tumor tissue was compared to adjacent non-tumor tissue, a remarkable similarity in miRNA dysregulation was observed between these samples, indicative of intrahepatic metastasis. These findings indicate the possibility of determining the histological grade of ICC by profiling miRNA dysregulation, which not only would greatly enhance the molecular diagnosis of ICC, but could even lead to the personalized the treatment for ICC by the early classification of histological grade. A total of 46 unique liver tissue samples were analyzed on Agilent human miRNA microarray (miRBase Release 16.0). Of the 46 samples, 13 are from non-cancer healthy patients with gastric bypass surgery. The rest of 33 samples are CCA tumor tissue samples and their paired adjacent normal/necrotic tissue: 12 from well differentiated CCA, 17 from papillary CCA, 4 from moderately differentiated CCA.

ORGANISM(S): Homo sapiens

SUBMITTER: Jeffrey Bethony

PROVIDER: E-GEOD-53992 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini.

Plieskatt Jordan L JL Rinaldi Gabriel G Feng Yanjun Y Peng Jin J Yonglitthipagon Ponlapat P Easley Samantha S Laha Therawach T Pairojkul Chawalit C Bhudhisawasdi Vajarabhongsa V Sripa Banchob B Brindley Paul J PJ Mulvenna Jason P JP Bethony Jeffrey M JM

Journal of hepatology 20140603 4

<h4>Background & aims</h4>Intrahepatic cholangiocarcinoma (ICC) is a significant public health problem in East Asia, where it is strongly associated with chronic infection by the food-borne parasite Opisthorchis viverrini (OV). We report the first comprehensive miRNA expression profiling by microarray of the most common histologic grades and subtypes of ICC: well differentiated, moderately differentiated, and papillary ICC.<h4>Methods</h4>MicroRNA expression profiles from FFPE were compared amon ...[more]

PMID: 25017828

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Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling we demonstrated that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 non-redundant genes that significantly discriminate the tumor stroma from non tumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix and Transforming Growth Factor beta (TGFM-NM-2) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increase expression of Collagen 4, Laminin, Osteopontin/SPP1, KIAA0101 and TGFM-NM-22 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of Osteopontin, TGFM-NM-22 and Laminin in the stroma of ICC was significantly correlated with patient overall survival. More importantly, multivariate analysis demonstrated that the stromal expression of Osteopontin was an independent prognostic marker for overall and disease-free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidates biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. 20 RNA samples were analyzed, from 10 patients with ICC. For each patient, RNA were isolated from laser capture microdissected (LCM) stroma from tumor and non tumor areas.

Dataset Information

The miRNAome of O. viverrini induced cholangiocarcinoma by microarray:

Publications

Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini.

Similar Datasets

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