LUNG MICROMET · Identification of molecular signatures determining early metastatic spread of lung carcinomas in women
6РП — Действия „Мария Кюри“
- Период
- 2005-07-01 → 2007-06-30
- Финансиране от ЕС
- 157 630 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Молекулярните белези при рак на белия дроб се анализират чрез търсене на разпръснати туморни клетки в костния мозък. Това помага да се разберат ранните процеси на разпространение на рака, които са невидими при стандартните клинични прегледи.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - LUNG MICROMET (Identification of molecular signatures determining early metastatic spread of lung carcinomas in women)
Despite some improvements in treatment, mortality among lung cancer patients still remains extremely high, with the five-year survival rate being currently only around 15 %. In most cases, mortality is linked to metastasis, the spread of cancer cells to regional lymph nodes (LN) and distant organs such as liver, brain or the skeleton. Notably, approximately 30 to 40 % of patients with non-small cell lung cancer (NSCLC) without clinical signs of either LN or distant metastasis at the time of the primary surgery have a relapse within 24 months. Disseminated tumour cells (DTC) or micrometastases may thus have been present at the time of resection of the primary tumour, but undetectable by current clinical processes. Therefore, understanding the very early molecular processes in the metastatic cascade is of crucial interest. No study has so far, to our knowledge, linked the presence of specific molecular changes with early lung cancer dissemination. In this EU- Marie Curie project, the aim was to assess whether the invasiveness and early metastatic spread of primary pulmonary tumours were associated with specific molecular patterns. As a marker for early spread we investigated disseminated tumour cells (DTC) in bone marrow (BM). Through using a high-resolution comparative genomic hybridisation (CGH) and expression arrays we performed genome wide DNA aberration and expression profiling of primary lung tumours. The genomic aberration profiles of the tumours from patients with and without DTC in the BM were then compared in order to find specific molecular changes associated with DTC status. We could find, for the first time, tumour-specific genetic signatures involved in early hematogeneous dissemination of lung tumours. We also identified five chromosomal regions differentiating BM-negative from BM-positive patients. Copy number changes on chromosome 4q were the most prominent finding, containing the highest number of differentially expressed genes. In BM positive patients 4q was mostly lost, whereas some gains could be found among BM negative patients. Interestingly, loss of 4q was also associated with formation of distant metastases. The same loss was also found to be common in brain metastases from both small and non-small-cell lung cancer patients. In conclusion, to our knowledge, this is the first study identifying tumour-specific genomic signatures involved in the early hematogeneous dissemination of lung tumour cells. Furthermore, we could show that loss of 4q might also be an important determinant for outgrowth of distant metastases. It will thus be an important goal in future studies to identify the target gene within 4q and explore its functional relevance.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Lung cancer is the most common lethal cancer type in the world, causing approximately one million deaths a year. In most cases mortality is linked to metastasis. Epidemiological data indicate that women are more susceptible compared to men for contracting lung cancer. Additionally, women tend to get mostly pulmonary adenocarcinomas, which is harder to detect by even invasive diagnostic techniques such as bronchoscopy. Reasons for these gender differences are largely unknown.Bone marrow is a common homing or gan for early disseminated lung cancer cells, with up to 50% of tumours not showing any metastases in lymph nodes still having micrometastatic cells in their bone marrow. These cells can be detected by sensitive immunocytochemical assays and their presence predicts the subsequent occurrence of overt metastasis. Recent results have shown that systemic dissemination of breast tumour cells via the blood circulation appears to be an early and selective process associated with specific molecular signature of the primary tumour.In the proposed project, we plan to use lung cancer as a tumour model, and perform a genome-wide expression and genetic screening of primary tumours and relate our findings to the capacity of early tumour cell dissemination. We will focus o n a well-defined group of female smokers because so far little is known on the particular biology of lung carcinomas in this growing group of patients. By comparing carefully selected tumours with and without micrometastasis, we expect to identify genetic determinants and regulatory pathways driving metastatic spread of epithelial tumours. We will use mainly different state-of-the-art high-throughput microarray-methods in combination with novel analysis for micrometastasis detection. Finding those patients whose tumours will most likely spread before the manifestation of distal overt metastases would be of great importance in the design of targeted treatment of these patients.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITÄTSKLINIKUM HAMBURG-EPPENDORF (UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF) · HAMBURGКоординаторНиво градГермания
Връзки
Данни: CORDIS, © Европейски съюз