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M.M. Bjaanæs
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-060 - Pathways Involved in Lung Adenocarcinomas, - Integrated Analyses on Methylation and mRNA Data (ID 2699)
09:30 - 09:30 | Author(s): M.M. Bjaanæs
- Abstract
Background:
Lung cancer is one of the biggest cancer killers in the world. Despite certain recent advances, mortality is still high. Targeted therapy has increased the time to death for metastastic lung cancer, but such therapy is not available for all lung cancer patients. Targeted therapy is more often available for never smokers, due to presence of druggable driver mutations. In order to search for new putative targets of therapy, we seek to identify pathways involved different subgroups of patients and in patients with early relapse.
Methods:
A total of 190 patients undergoing surgery for lung cancer were included in the study (154 EGFR positive, 23 EGFR negative, 170 smokers and 20 non-smokers). Lung cancer tissue and clinical information was available for all patients and normal lung tissue was available for 30 of the patients. Whole genome expression array analysis (Agilent) was performed using mRNA isolated from all samples and DNA-methylation was analysed for 168 tumours and 21 matched normal lung tissue samples. R was used for statistical analyses; annHeatmap (from Heatplus) for hierarchical clustering, limma to identify differentially expressed genes, SPIA for pathway analysis and canonical correlation of methylation and mRNA-expression was performed with the CCA function from the PMA package. Pathways with an FDR<0.1 were considered significant. DAVID was used for gene ontology analysis.
Results:
Based on correlation of mRNA and methylation, different pathways were identified as predominant in specific subgroups of lung adenocarcinomas. Preliminary results indicate that genes involved in the KEGG-pathways cell cycle are more highly expressed in EGFR positive than in EGFR negative tumours in smokers. In the EGFR-negative tumours, several pathways are up-regulated: Oocyte meiosis, progesterone-mediated oocyte maturation, HTLV-1 infection, p53 signalling pathway and small cell lung cancer. For non-smoking patients, four pathways were up-regulated in EGFR-positive tumours: ECM-receptor interaction, TGF-beta signalling pathway, bile secretion and cocaine addiction. There were no pathways up-regulated in EGFR-negative compared with EGFR-positive never-smokers. This may partly be due to small numbers. Similarly, pathways dominating the tumours of patients with early relapse will be identified. Genes whose expression and methylation status were correlated were identified within smokers and non-smokers separately.
Conclusion:
Based on correlation between mRNA and methylation, specific pathways were identified activated in subgroups of lung adenocarcinomas. There are significant differences between ever-smokers and never-smokers. Survival analyses are ongoing.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-011 - Whole-Genome Copy Number Analyses of NSCLC Tumors Reveal Aberrations Associated With EGFR Mutations and May Have Prognostic Impact (ID 1504)
09:30 - 09:30 | Author(s): M.M. Bjaanæs
- Abstract
Background:
Knowledge about genetic alterations in Non-Small Cell Lung Cancer (NSCLC) has given us a significant insight in the biology of these tumors. It is of great clinical importance with consequences for the patients, and DNA mutations and translocations are currently targets for therapy. Aberrations in DNA copy number are frequent events in NSCLC tumors and important in tumorogenesis. In this present study we want to investigate how the copy number changes varies between different subgroups of NSCLC tumors based on the patients’ smoking status, histology or EGFR-, KRAS- and TP53 mutations. The DNA copy number data will be integrated with global mRNA expression to study the cis-associated mRNA expression changes. Last, we want to investigate whether genomic events, like specific copy number changes or the complex arm-wise aberration index (CAAI), have prognostic impact in patients with NSCLC.
Methods:
In this study we have included 200 patients with operable NSCLC tumors. Copy number data were obtained by using the Affimetrix Genome-wide human SNP array 6.0. Histopathological information, EGFR-, KRAS- and TP53 mutation status were determined and clinical information and follow-up data was obtained for all patients. The mRNA expression was determined by the Agilent 60K mRNA expression array on a subset of 117 patients. The data was analyzed by using bioinformatic tools like ASCAT and integration of the mRNA data and the survival analyses are on-going.
Results:
Preliminary results have shown that copy number aberrations are frequent events in NSCLC tumors, consistent with previous reports. We have identified that the copy number patterns differ between adenocarcinomas and squamous cell carcinomas, and between tumors from patients with different smoking history. However, the largest differences were found between the EGFR-mutated adenocarcinomas compared with EGFR wildtype tumors, where we identified a specific pattern of copy number changes in the tumors that harbour EGFR mutation. These changes were mainly located at chromosome arm 1p, 2p, 3q, 5q, 7, 12 and 13. Preliminary analyses have also identified specific copy number aberrations with prognostic significance.
Conclusion:
Copy number aberrations are frequent in NSCLC tumors and may have great impact on gene expression and give us valuable prognostic information. EGFR-mutated adenocarcinomas have a specific pattern of copy number changes, which provides new insight of the biology of these tumors.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-011 - Unique Combination of 6 Circulating microRNAs for Early Detection of Lung Cancer (ID 2130)
09:30 - 09:30 | Author(s): M.M. Bjaanæs
- Abstract
Background:
Worlwide, lung cancer is the primary cause of cancer death. Today 75% of patients are diagnosed in a locally advanced or metastatic inoperable stage, and a new tool for early detection of lung cancer is urgently needed in order to improve the outcome. Circulating microRNAs have emerged as stable, non-invasive and promising biomarkers for diagnosis, prognostication and prediction in cancer. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy normal individuals.
Methods:
We profiled the expression of 756 unique microRNAs in sera from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers, to explore the potential of the microRNAs as diagnostic biomarkers. For validation of our results, we analyzed serum from an independent cohort of high-risk individuals enrolled in the IELCAP screening trial (n=161) using RT-qPCR
Results:
Focusing on microRNAs upregulated in sera from lung cancer patients, we identified a unique set of 6 microRNAs with significantly higher abundance compared with sera from COPD patients and healthy normals. Validation of the 6-miR signature demonstrated a sensitivity of 86% and specificity of 79.3%
Conclusion:
Considering their accessibility and stability, circulating microRNAs can be a diagnostic tool for clinicians in the future, and may lead to increased fraction of lung cancers diagnosed in an early curative stage. The 6-miR signature may be a basis for a screening study and can easily be implemented in the clinic to identify those who should be further examined for lung cancer
