Lung Cancer Proteomics

Luigi De Petris, Anders Nordström , Pia Baumann, Maria Pernemalm, Lukas Orre, Sara Ståhl, Birgitta Sundelin, Flavia Melotti and Rolf Lewensohn.

Lena Kanter, Göran Elmberger (Pathology); Eva Brandèn, Hirsh Koyi (Lung Medicine); Per Bergman, Lotta Orre (Thorax Surgery); Signe Friesland (Oncology); Mathias Uhlèn (HPR).

Lung cancer (LC) is a major cause of cancer related death worldwide. In Sweden, lung cancer is the second most common cause of cancer-related death in both men (after prostate cancer) and women (after breast cancer). A nation-wide campaign against smoking, developed more than 20 years ago, has substantially decreased the incidence of lung cancer in Sweden, which is now approximately 1/3 compared to southern Europe. This has also changed the features of this disease, in that it shows a higher prevalence in women and non-smokers compared to other countries.

The lung cancer proteomics projects at Karolinska Biomics Center are directed towards a global understanding of the disease, and are based on an internal expertise in molecular mechanisms and proteomics technologies, and external collaboration with the Biobank, and the Units of Lung Medicine, Thorax Surgery, Oncology at Karolinska University Hospital. Under these collaborations, we have been collecting clinical samples (including blood and tumor tissue) from lung cancer patients since 2004. This sample collection is done according to SOPs (Standard Operation Procedures) properly developed to optimally preserve the intact sample proteome. In the control group, patients with benign lung diseases, as well as lung metastasis from other tumors, are included.

Discovery phase

The discovery phase includes proteomics profiling of diverse LC cell lines and freshly frozen tumor tissue as well as plasma with mass spectrometry based proteomics (both SELDI-MS and LC-MALDI). The main research questions include the identification of specific lung cancer markers (tissue), markers for early diagnosis (plasma), prognostic markers (plasma) and markers predictive of response to treatment (cell lines).

Validation phase

Once a protein of potential clinical interest has been identified, its distribution in lung cancer is assessed using an Ab-based method (mainly IHC) on a tissue microarray. At KBC we have collected a TMA that contains representative cores from 100 stage I NSCLC samples. The fast and reproducible TMA technology gives important information about the distribution of the marker among the diverse NSCLC histologies. Moreover, the complete clinical data and long follow up available for these cases will give a preliminary information about the potential prognostic role of the marker.

Last updated: 2008-01-12