Author of

• 11481

  +

  P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11501

    +

    P2.02-020 - MicroRNA deregulation associated with node positive lung adenocarcinoma (ID 3426)

    14:53 - 15:10  |  Author(s): V.R. Ramnarine
    • Abstract

    Background
    Lung cancer is the leading cause of cancer-related deaths worldwide, with poor survival largely attributed to late stage of disease at diagnosis and frequent metastasis. Typically, tumor cells colonize the regional lymph nodes before spreading to distant sites, significantly dampening prognosis. The presence and number of affected nodes can be detected by routine imaging procedures, but occasionally, additional affected nodes are not detected until time of surgery, which impacts staging. The identification of biomarkers that stratify node positive (NP) and node negative (NN) patients could improve detection of aggressive disease, while a deeper understanding of the underlying biology of NP lung cancer could lead to the design of novel therapeutic interventions. MicroRNAs (miRNAs) are major regulators of gene expression that control a wide range of cellular processes, and have been shown to be excellent biomarker candidates due to their stability in biofluids. The role of miRNA deregulation in NP lung cancer is poorly understood; therefore, we sought to compare miRNA expression levels of lung adenocarcinoma (AC) cases with and without nodal involvement in order to identify miRNAs associated with tumor aggressiveness. We hypothesize that a subset of miRNAs are specifically deregulated in NP AC, representing potential biomarkers, and that identification of miRNA-mRNA interaction networks will shed light on the biological mechanisms of tumor spread that may be therapeutically exploited.

    Methods
    A panel of 45 NN and 28 NP primary AC tumors were collected along with paired adjacent non-malignant tissues. All samples underwent expression profiling of miRNA (Illumina GAIIx small RNA sequencing) and mRNA (Illumina microarray). NN and NP groups were analyzed separately as follows: matched tumor and normal miRNA normalized read count comparisons were performed (Wilcoxon Signed-Rank test, Bejamini-Hochberg corrected p<0.05), and miRNAs that were significantly deregulated in tumors were further investigated. miRNA fold changes (FC) were calculated on a case by case basis, and FC values were then compared between groups (Mann Whitney U Test p<0.05). miRNAs that (i) displayed a minimum 2-fold frequency of disruption >50% of NP cases, (ii) had a median FC>2 in the NP group, (iii) had a Signed-Rank corrected p<0.05, and (iv) had a MWU p<0.05 were considered to be NP-specific. Target prediction analysis of these miRNAs was then performed, and mRNA expression data was utilized to ensure predicted target expression was anti-correlated with miRNA expression. Candidate targets were input into Ingenuity Pathway Analysis to determine pathways implicated in NP AC.

    Results
    Fourteen miRNAs were NP-specific according to our criteria. These miRNAs included those previously associated with biology and metastasis of epithelial cancers, as well as miRNAs novel to lung AC. Target analysis implicated several pathways and functions previously associated with a metastatic phenotype such as the TGFβ pathway.

    Conclusion
    These results indicate that miRNA expression differs between NP and NN lung AC, further demonstrating the involvement of miRNAs in the regulation of the metastatic process. The role of these miRNAs as prognostic markers and serum biomarkers, as well as the mechanism of action of these miRNAs in AC biology must be further explored.