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A.R. Halvorsen
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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): A.R. Halvorsen
- 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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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-125 - Cytokine Profiles in Non-Small Cell Lung Cancer Patients Undergoing Palliative Thoracic Radiotherapy; Predictor of Response? (ID 2588)
09:30 - 09:30 | Author(s): A.R. Halvorsen
- Abstract
Background:
A majority of patients with non-small cell lung cancer are diagnosed in later stages of disease where no curative treatment is currently available. The prognosis for these patients is poor. Median survival from diagnosis in stage IV is approximately 9 months. Many patients will benefit from external radiotherapy to the thorax for alleviation of symptoms due to advanced lung cancer. Despite adequate radiotherapy, however, many tumors progress locally in the radiation field. Here, we investigate whether the kinetics of cytokines in serum can be utilized as predictors for tumor response to radiotherapy and/or predictors of lung toxicity.
Methods:
Patients with histologically confirmed non-small cell lung cancer, eligible for palliative radiotherapy to the hilus-mediastinum, were included in a randomized phase II clinical trial; the ThoRaT-study. Patients were randomised to 1 of 2 study arms undergoing thoracic radiotherapy, 3 Gy x 10, with or without the addition of erlotinib concomitant with radiotherapy treatment. Side effects were recorded and graded according to CTC version 4.0. Clinical response in the radiation field was evaluated by CT or PET-CT scans. Blood serum was sampled at different time points; prior to treatment, at mid-therapy, at the end of therapy and 6 week following treatment completion. Multiplex immunoassays were used to measure serum concentration of 52 cytokines and 9 MMPs on all collected samples. Serum samples from COPD patients were included as controls.
Results:
Cytokine analyses of serum samples are ongoing and have to date been performed on 43 non-small cell lung cancer patients. Pre-treatment and follow up CT/PET-CT scans are currently under revision. Preliminary investigations show considerable variation in cytokine patterns between the patients and between different time points for some of the cytokines. Analyses of possible predictors for radiotherapy response and toxicity, as well as comparison with normal controls are currently ongoing and will be presented.
Conclusion:
We hypothesize that pre-treatment cytokine values and/or kinetics of concentration changes may provide information on the probability of clinical response and side effects from radiotherapy.
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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): A.R. Halvorsen
- 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
