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Sana Yokoi



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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-063 - Oncogenic microRNAs Associated with Poor Prognosis Are Up-Regulated on the Amplicon in Squamous Cell Lung Carcinoma (ID 9901)

      09:30 - 16:00  |  Presenting Author(s): Sana Yokoi

      • Abstract

      Background:
      Squamous cell carcinoma (Sq) is second major histological subtype of lung cancer. Unlike in the case of adenocarcinoma (Ad), Sq has only few molecular target drug. MicroRNA (miR) is a major part of post-transcriptional regulators functioning as tumor suppressor genes or oncogenes. MiR will regulate target molecules related to carcinogenesis and malignancy in Sq.

      Method:
      Using The Cancer Genome Atlas dataset including copy number variation, RNA sequence, miR sequence, clinicopathological feature from 484 lung cancer cases, the correlation between genomic copy number and expression of miR was analyzed. 245 samples of Sq and 239 samples of Ad were included. The raw counts of each mature miR fragments with different precursor were merged and calculated from miR-seq isoform files by R project (http://www.r-project.org/) Segmented copy number variation datasets were processed with R package CNTools of Bioconductor project. Independent two-group Mann-Whitney U test was used to compare different expression between Sq and Ad. MiR expression according to copy number variation was analyzed using Pearson correlation coefficient r-score. To identify the miR target sites of mRNAs, targetscan-Perl scripts were used (http://www.targetscan.org/).

      Result:
      From 1,001 mature miR fragments, 34 miRs were identified as the candidates especially for Sq distinguished from Ad. Furthermore, four miRs were up-regulated in amplified regions and independently associated with poor prognosis in Sq. Moreover, those who had the tumor with high expression in three of four miR simultaneously showed worst prognosis. To explore miR-mRNA network, we also predicted the target genes for each miR. From 734 common target genes, three showed positive correlation with the expression of three miRs. Among them, the expression of 109 mRNAs inversely correlated with that of 3 miRs. From 109 mRNA, the expression of 24 mRNAs inversely correlated with that of all the 3 miRs and only 2 mRNA expression showed low levels in Sq compared with Ad or normal tissues.

      Conclusion:
      Three miRs up-regulated in Sq were associated with poor prognosis through the regulation of two common target genes.