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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-10 - Transcriptomic Differences Between Early and Late Stage Lung Adenocarcinoma (ID 13656)

      12:00 - 13:30  |  Author(s): Nan Li

      • Abstract
      • Slides

      Background

      Early and late stage lung adenocarcinoma patients differ significantly in overall survival. The tumor progression to advanced stage is driven by tumor genomic variation and the resulted abnormal gene expression profiles. A thorough study of molecular expression profiles between early and late stage lung adenocarcinoma will greatly contribute to the understanding of progression mechanism and biomarker discovery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We used RNA-seq to investigate the gene expression differences of 17 fresh frozen tissue samples, which were collected from 7 early (IA) and 10 late stage (IIIA, 3; IIIB, 2; IV, 5) lung adenocarcinoma patients.

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 232 protein coding genes show differential expression levels between early and late stage subgroups. Gene functional annotations show that the differentially expressed (DE) protein coding genes are enriched in multiple KEGG pathways: pancreatic secretion, nicotine addiction, neuroactive ligand-receptor interaction, circadian entrainment, amphetamine addiction, and serotonergic synapse. The majority of pathway enriched DE genes (16 of 24) are translated into transmembrane proteins, such as ADCY2 (high in early) and GRIN2B (high in late) etc., with no correlation between expression level and certain stage. For cancer driver genes, ALK and NTRK2 show higher expression levels in late stage than in early stage. ERBB4 shows lower expression level in the late stage We also identified a group of keratin family genes (KRT2, KRT6A, KRT6B, KRT14, and KRT16) with higher expression levels in the late stage lung adenocarcinomas; Interestingly, keratin expression level distinguishes the subgroups of solid tumors in other cancer types. Though ERBB2, PIK3CA, and TP53 were not identified as differentially expressed genes, their expression variations in the late-stage samples are significantly larger than those in the early stagewhich could be a result of regulatory network change along the progression of tumor. Furthermore, 79 non-coding RNA were identified as DE “genes”. Among them, four previously studied ncRNA prognostic markers: MIR31HG, DRAIC, LUCAT1, and LINC00261 were also identified as DE “genes” with consistent expression-stage relationship comparing with the previous report. Two other ncRNA, VLDLR-AS1 and LINC01919, are highly expressed in early stage samples and may serve as potential prognostic markers for lung adenocarcinoma.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study investigated the gene expression differences between early and late stage lung adenocarcinomas and identified differential expressed coding genes and non-coding genes, which will provide potential target information for the diagnosis and clinical intervention of lung adenocarcinoma patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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