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W. Cookson



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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-054 - The Molecular Characterisation of Lung Adenocarcinoma Subgroups (ID 9412)

      09:30 - 16:00  |  Author(s): W. Cookson

      • Abstract

      Background:
      Lung adenocarcinoma is a heterogeneous disease which can be challenging to classify accurately, yet precise histological subtyping is becoming increasingly important. Subgroup patterns have been shown to confer important prognostic information. In this study, we sort to identify gene expression profiles for the six predominant subtypes within adenocarcinoma, in a sequential cohort of resected tumours, to explore whether molecular markers could enhance standard histological diagnosis.

      Method:
      89 paired (fresh frozen tumour and normal tissue) lung adenocarcinomas were profiled both histologically and by global gene expression and correlated with multiple clinical parameters including stage, age, gender and smoking status. The tumour samples were reviewed by a thoracic pathologist to determine the predominant subtype and assigned into lepidic, acinar, papillary, micropapillary, solid or cribriform predominant groups. Gene expression was generated using Affymetrix Human gene 1.1ST arrays and the Genetitan platform. All RINs > 6. The data was rma treated using Affymetrix Power Tools and poor quality arrays were detected and excluded using Array Quality Metrics. Low expressed probes and control probes were removed. Differential gene expression of the adenocarcinoma predominant subtypes was evaluated using Limma.

      Result:
      Survival analysis confirms that age and stage are the most significant predictors of outcome. Application of a highly stringent threshold (adj. P value 0.0001) identified 4805 gene transcripts that were significantly differentially expressed among the six predominant adenocarcinoma subtypes. We determined that 3887 of these transcripts are unique to one of the adenocarcinoma subgroups and therefore have the potential to contribute to a predominant subtype defining transcriptional signature. These unique transcripts include functionally interesting genes such as transcriptional factors SOX2/4/7/13/18 involved in determination of cell fate and ROR1 a receptor tyrosine kinase-like orphan receptor among others. A pairwise comparison of the individual subgroups identified that the most significant gene variation is seen between lepidic predominant and solid predominant, indicating that these subgroups are transcriptionally the most disparate to one another.

      Conclusion:
      In this study multiple highly significant gene transcripts that allow differentiation between the adenocarcinoma subgroups have been identified. These adenocarcinoma subtype gene signatures have the potential to augment current histological diagnosis of lung adenocarcinoma and provide valuable insights into the different biological processes underpinning the six adenocarcinoma subtypes.