Changes in gene activity indicate lung cancer in its early stage
Unclear disease symptoms of the lung and respiratory tract need to be clarified by a CT scan. How malignant are the nodules that are discovered this way? Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), the Hospital for Thoracic Diseases (Thoraxklinik) Heidelberg and the National Center for Tumor Diseases (NCT) Heidelberg are searching for biomarkers to help evaluate such findings. They studied cells taken from the surroundings of suspicious lesions, looking for cancer-typical genetic changes. The tenascin C gene attracted their attention, because it is significantly more active in the vicinity of malignant nodules than in samples without pathological findings. Its increased gene activity might be used for enhancing the diagnosis of lung tumors.
Patients with unclear symptoms of the lung and respiratory tract are frequently referred to spiral computed tomography (CT) scans. In such CT scans, physicians often discover individual suspicious pulmonary nodules. Fortunately, these so-called “round lesions” are often not malignant. However, if there is a suspicion of such a severe disease as lung cancer, it is vital that such a finding be clarified reliably.
Researchers in the team of Ruprecht Kuner and Holger Sültmann of DKFZ, NCT and the Hospital for Thoracic Diseases, all located in Heidelberg, were searching for biomarkers that might help physicians determine the nature of such tissue abnormalities. Their hypothesis was to find cells in the close vicinity of a suspicious nodule whose altered gene activity might be an indication of a malignant tumor.
The group studied bronchoscopic microsamples of 71 patients with suspicious nodules. The samples – cells and bronchial fluid from the close vicinity of a suspicious lesion – were collected during a bronchoscopy exam which was necessary for medical reasons. Taking such a microsample with a tiny brush is much less stressful for the patient than surgical removal of a tissue sample. Microsamples collected from the other lung without findings were used as controls.
Four genes that are involved in many cancers were found to have a significantly increased activity in samples from the surroundings of lung cancer compared to samples from the vicinity of round lesions that turned out to be benign. The researchers found the most significant association with lung cancer for the gene coding for the tenascin C glycoprotein. In a healthy organism, tenascin C occurs primarily during embryonic development, but it is also found in some cancers around the tumor. „In the samples of the lung without finding, there was almost no difference in the activity of the tenascin C gene between study participants with benign nodules and those with malignant ones,” Ruprecht Kuner explains. „Therefore, strong activation of tenascin C may be a clear indication of a malignancy. “ The predictive value of tenascin gene activity may be further increased by combining it with other parameters such as the size of the nodule. The investigators are now planning to validate the reliability of this biomarker in a larger group of patients.
Nicolas Kahn, Michael Meister, Ralf Eberhardt, Thomas Muley, Philipp A. Schnabel, Christian Bender, Marc Johannes, Denise Keitel, Holger Sültmann, Felix JF. Herth and Ruprecht Kuner: Early Detection of Lung Cancer by Molecular Markers in Endobronchial Epithelial Lining Fluid. Journal of Thoracic Oncology, 2012, DOI: 10.1097/JTO.0b013e31824fe921
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.