We recently reached out to some of the DIOPTRA partners who are leading various activities to gain their perspectives on the project’s mission from their areas of expertise. This resulted in a series of video interviews that will be available on our website and official YouTube channel, where they share insights into their challenges and ongoing work.
Our third interview features Christos Fotis, Chief Innovation Officer at Protavio, giving us an overview on a key piece of the puzzle faced by DIOPTRA: the quest to identify those protein biomarkers that would allow to detect colorectal cancer.
Here below, an extended transcript of the interview:
What is the role of your organization in the project?
The role of Protavio is very important in the DIOPTRA project. Our goal is simple, but is very important. Our goal is to discover a set of protein biomarkers that are present in blood that can be used to differentiate between the DIOPTRA study groups, or the study populations that we have in DIOPTRA, which are people that are healthy, people that have known neoplastic findings in colonoscopies, and people that have advanced neoplastic findings: this final group is the group that has colorectal cancer.
And how does this translate into a pipeline?
In order to identify and discover these novel protein biomarkers, we are analysing matched samples from DIOPTRA participants: matched meaning we are analyzing both tissue samples and blood samples from the same participant. The blood samples are collected prior to the colonoscopy and the tissue samples are collected during the colonoscopy, in the samples that the gastroenterologist finds during the procedure. For the blood samples, we are doing a proteomics analysis, and for the tissue samples who are doing a transcriptomics analysis. So this biomarkers discovery pipeline that we are developing – which is very novel and state of the art – has what we call a multi-omics approach, because we combine both proteomics from the blood samples and transcriptomics from the tissue sample.
What have you discovered so far?
So far we’re in the discovery study phase of the project. So we are collecting all these samples, and we are almost finished with the sample collection – we only need a few colorectal cancer cases – and we have developed, of course, the pipeline. We have set up all the instrumentation for the pipeline, which is both for the proteomics and the transcriptomics. We have developed all the protocols and validated most of the protocols for some samples that we have available, so far, and we have optimized everything. So the final thing now is to collect all the data, collect all the samples, and do the final experimental design, where we will do all the proteomics analysis – and transcriptomics – according to the pipelines that we have optimized. The important part of the biomarker discovery pipeline is that it is very novel, because it uses state of the art technologies like Olink proteomics and RNA sequencing. For Olink proteomics, so far we have received the certification from the provider of the Olink methodology, and we are also running experiments in our labs in Athens with the same samples that Olink is also analyzing in their main facility in Uppsala, Sweden, to verify the concordance of our measurements: so we are sure that the quality of the data that we are producing for DIOPTRA is at the utmost standard of quality.
When do you expect to have the first results?
So far, we have organized the first pilot experiment – which is a feasibility study of this whole pipeline – where we will analyze 88 samples, but not with the full potential of the biomarker discovery pipeline. We will measure a limited number of biomarkers instead of the 3000 that we planned to measure for the project; we will measure 400 biomarkers that have to do with oncology. So our goal is to validate all the processes that we have developed so far with these 88 samples, to see that everything works correctly. And then we would do the design of the final discovery experiment by September, and we will have the full discovery dataset by the end of the year along with the analysis.
One final question: how do you pinpoint those biomarkers that are connected to colorectal cancer?
In the discovery pipeline, the first approach is to be as broad as possible. So we measure a plethora of biomarkers, let’s say 300. And then we do a computational analysis of those results to identify those biomarkers in blood that show a statistical difference in their expression and orientation between the different DIOPTRA study groups. But then we enhance that. We use the term multi-omics approach because, for the protein measurements from the blood samples, we also have the RNA sequencing measurements from the tissue samples. So there comes the multi-omics approach, where we first select the protein biomarkers that show a statistically significant difference. But then, because we analyzed the tissue samples from those very same participants, we can prioritize those biomarkers in blood that are associated with the gene expression that we can see in the original tissue. So our biomarker discovery pipeline has a mechanistic approach, as we say. We don’t only look for statistical associations, but we also look for associations to the mechanism of the disease, the mechanism of the initiation of the colorectal cancer in the original status that the initiates in the tissue samples of the colon of the patients.
Curious to see how this side of the DIOPTRA research connects with the other angles explored by the project? Check out also our interviews on the DIOPTRA Prospective and Retrospective Studies, and on the clinical field’s perspective.