A research team led by Nuno Barbosa Morais, group leader at Instituto de Medicina Molecular João Lobo Antunes (iMM) in Lisbon, computationally analysed the expression of marker genes that are associated with a “fingerprint” of cancer cells in thousands of tumors and revealed its therapeutic potential in the fight against cancer. The study published today in the scientific journal PLoS Computational Biology shows the types of tumors in which these genes are most active and identifies drugs with the potential to selectively eliminate cells that carry that label.
The centrosome is an organelle present in all animal cells that is fundamental in several cellular processes, such as division, migration and communication between cells. For more than a century it has been proposed that the abnormal increase in the number of these structures could induce cancer and since then, the increase in the number of centrosomes is seen as one of the hallmarks of cancer cells and is the subject of the scientists’ attention. The technical difficulties in characterising this abnormality in patient samples have prevented its clinical potential and being explored on a large scale. To bypass this, the team led by Nuno Barbosa Morais at iMM looked at the expression of genes that cause this increase and analysed its incidence in thousands of tumors of different types of cancer and in normal tissue samples from the same patients. “The results revealed that this signature is present only in tumor samples and is more prevalent in aggressive forms of cancer,” explains Nuno Barbosa Morais, adding “more importantly, a higher expression of these genes is associated with a lower survival rate in different types of cancer. “
Using drug sensitivity studies, the scientists also identified selective compounds for cells with this abnormality that could be targeted specifically against cancer cells, not affecting the healthy cells of patients. “Additionally, the samples that we have analysed are now characterised at the levels of their DNA sequence and the expression of thousands of genes. This means that the integration of this data allows us to better understand the causes and molecular consequences of this increase of centrosomes in our cells”, explains Bernardo de Almeida, the first author of this study.
“The next steps are now to translate the expression data of the genes that cause this “fingerprint” into support information for clinical decision. We also intend to validate the efficacy of the drugs identified by our computational approach as having greater therapeutic potential. These are studies that will naturally involve collaborations with colleagues who are specialists in clinical oncology and pharmacology”, says Nuno Barbosa Morais, group leader and supervisor of the study.
This study involved a collaboration with the team of Joana Paredes at i3S – Institute of Research and Innovation in Health of Porto and with Mónica Bettencourt Dias, from the Instituto Gulbenkian de Ciência. The work was funded by the European Molecular Biology Organization (EMBO) and the Portuguese National Council, Fundação para a Ciência e a Tecnologia (FCT).
*Bernardo P. de Almeida, André F. Vieira, Joana Paredes, Mónica Bettencourt-Dias, Nuno L. Barbosa-Morais (2019) Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome. PLoS Computational Biology.