Project description:Objective: Globally, esophageal cancer is among the most deadly cancer forms. Long non-coding RNAs (lncRNA) are frequently found to have important regulatory roles. We aim to assess the lncRNA expression profile of esophageal squamous cell carcinoma (ESCC) and identify prognosis related lncRNAs. Design: LncRNA expression profiles were studied by microarray in paired tumor and normal tissues from 119 ESCC patients, and validated by qRT-PCR. The 119 patients were subsequently divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random forest supervised classification algorithm and a nearest shrunken centroid algorithm, and validated in test group and further in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by Multivariable Cox regression analysis. Results: LncRNAs showed significantly altered expression in ESCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885•1, XLOC_013014, and ENST00000547963•1) which classified the patients into two groups with significantly different overall survival (median survival 19•2 months vs. not reached, p<0•0001). The signature was applied to the test group (median survival 21•5 months vs. not reached, p=0•0030) and independent cohort (median survival 25•8 months vs. not reached, p=0•0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for ESCC patients. Stratified analysis suggested that the signature was prognostic within clinical stages. Conclusions: Our results suggest that the three-lncRNA signature can serve as a novel biomarker for the prognosis of ESCC patients. Application of it allows for more accurate survival prediction. The lncRNA expression profiles of cancer and adjacent normal tissues form 119 ESCC patients were studied by microarray and an lncRNA signature that can perdict the survival of ESCC patients was identified.

Project description:Mammals express thousands of long noncoding (lnc) RNAs, a few of which are shown to function in tissue development. However, the entire repertoire of lncRNAs and the extent to which they regulate biological processes in different tissues and species are not defined. Indeed, most lncRNAs are not conserved between species, raising questions about function. We used RNA-Seq to identify lncRNAs in primary murine fetal liver erythroblasts expressing the lineage marker TER119, megakaryocytes (CD41+) cultured from embryonic day (E) 14.5 murine fetal liver and megakaryocyte erythroid progenitors (MEPs) isolated from mouse bone marrow. We identified 683 and 594 polyadenylated lncRNAs expressed in red blood cell (erythroid) precursors of mice and humans, respectively. More than one half of erythroid lncRNAs are un-annotated, emphasizing the opportunity for new discovery through studies of specialized cell types. We analyzed the expression of these identified lncRNAs in several hematopoietic compartments using a custom microarray to identify erythroid-specific lncRNAs that were robustly expressed in both fetal liver and adult erythroid cells as targets for knockdown. Over 90% of fetal liver erythroid lncRNAs detected using RNA-seq were expressed in adult erythroblasts measured on the microarray. Analysis of the murine erythroid lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by the key erythroid transcription factors GATA1 and SCL/TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatically greater species-specificity than coding genes. We investigated potential functions of 21 relatively abundant erythroid-specific murine lncRNAs (both conserved and non-conserved) by RNA interference in primary mouse erythroid precursors, and identified 7 whose knockdown inhibited features of terminal erythroid maturation including cell size reduction and enucleation. Strikingly, at least 6 of the 7 lncRNAs have no detectable expression in human erythroblasts, demonstrating that lack of conservation between mammalian species does not predict lack of function. These results reflect marked evolutionary differences between protein-coding genes and lncRNAs and indicate that the latter exert tissue- and species-specific roles in development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf A custom Agilent microarray was designed to interrogate expression levels of long noncoding RNAs identified using RNA-seq in several different hematopoietic progenitor and differentiated cell populations. LncRNA gene definitions and RNA-seq data used to identify long noncoding RNAs are deposited in GEO with the accession numbers GSE51667 and GSE40522 respectively. The Agilent eArray platform was used to customize the SurePrint G3 Mouse GE 8x60K microarray to add 3 custom-designed probes (60nt length) each against several categories of genes, namely pseudogene, genes with small RNA overlap, low stringency lncRNAs and high stringency lncRNAs . We interrogated 7 types of hematopoietic cells, HSC, CMP, MEP, GMP, early and late erythroblasts and granulocytes. Expression measurements were determined at least in duplicate for all samples and in triplicate for most samples.

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Genome-wide screening of the expression of long noncoding RNA and coding RNA expression in esophageal sqaumous cell cancer

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