Scientists Moving Towards a Gene Biomarker for Tumors Prone to Metatasis
Using bio-banked tumor materials and clinical history for a decade of patient outcomes, researchers in Europe are making progress towards identifying a biomarker to identify lung cancer (and other) tumors most likely to go through metastasis, thus significantly worsening the prognosis for a person with cancer. ScienceDaily provides a cogent summary from the press release from the researchers:
"[T]he scientists concentrated their efforts on lung cancer. They examined the tumors of nearly 300 patients at the CHU de Grenoble. Over a ten year period, the physicians documented patients’ records and conserved and annotated tumors after surgical resection. The expression of all human genes was analyzed in these tumors and correlated with different clinical parameters.
Among the genes aberrantly expressed in lung cancers, they discovered 26 whose activation is associated with particularly aggressive cancers: when these genes are expressed, the cancer is extremely virulent. The researchers are thus able to predict, at the diagnosis stage, which cancers have a high risk of recurrence and a fatal prognosis, even in cases where the tumor is adequately treated, at an early stage of its development. These high-risk cancers exhibit increased proliferative abilities and a facility to "hide" from the body’s immune system.
This work provides a proof of principle for a new approach in the study and treatment of cancer: the aberrant expression in a tissue or organ of genes specific to other tissues could become a new tool for establishing a prognosis and personalizing therapeutic care. From a more fundamental viewpoint, the researchers still need to explain the relationship between the aberrant expression of these genes and the virulence of the cancer. An approach similar to that tested in lung cancer could be extended to virtually all types of cancer, opening very broad perspectives regarding the exploitation of these findings."
The full article is online at this page of Science Translational Medicine, and the abstract is pasted below.
"Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale “off-context” gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature–guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors."