Diabetes is a complex disease characterized by a combination of different and little understood, causes. The current classification system for the disease characterizes diabetes into three broad types: type 1 diabetes, type 2 diabetes, and gestational diabetes, but these three categories do not adequately reflect its sheer heterogeneity. This has severe negative implications for the planning of treatment regimens and identifying which patients are at risk of developing complications or comorbidities. Building on previous research which identified five novel diabetes subgroups in Scandinavian diabetes patient cohorts, this study sought to comprehensively characterize differences in inflammation biomarkers between these subgroups using Olink’s inflammation biomarker panel.
In its mission to accelerate proteomics together, Olink encourages the advancement of science through comprehensive support of its customers in their own studies to achieve better insight into their areas of research. Sometimes, this may be achieved through collaboration with other scientists in their fields. As a result, Olink has played a part in creating several consortia involving Olink customers with similar areas of interest, such as SCALLOP, where like-minded researchers work together to publish high-impact papers investigating the association of genes and proteins included in Olink protein panels.
With the advancement of available technologies in recent years, researchers are fast becoming aware of the advantages of using proteomics in their research to better understand human biology and disease and to drive pharmaceutical development towards new and improved therapies. Anders Mälarstig, the director of human genetics at Pfizer, came to this realization early on. While he began his research career using genetics to understand cardiovascular disease, he soon turned to proteomics, and specifically protein quantitative trait loci (pQTLs) to take his research one step further. In the following interview, Dr. Mälarstig makes the case for this proteogenomics approach to advance basic and clinical research and speaks to its advantages in the drug discovery and development space.
Dr. Andrzej Krolewski (Find his profile here), the head of the Genetics and Epidemiology section of the Harvard Medical School, has been working on the genetics of type 1 and type 2 diabetes. For the last 30 years, he has been actively investigating diabetic kidney disease in patient cohorts from the Joslin diabetes center, where he is also a researcher.
High-throughput multiplexed proteomic technology is leading the way to the latest developments in pre-clinical disease analysis in drug discovery. The pharmaceutical industry is now increasing its efforts in the discovery of novel drug targets by using protein quantitative trait loci (pQTLs), which allows for a more confident inference of disease causality and associated protein regulation. This has the potential to revolutionize the drug discovery process and a major academia-industry consortium is at the forefront of efforts to do just that.
The last two blog posts described how protein biomarker research is helping scientists better understand why some patients respond better to immunotherapy than others. Immunotherapy is not the only cancer treatment with a less than stellar success rate, however, as radiation and chemotherapy also elicit a varied response in patients undergoing treatment. For example, only about 25-35 % of stage three lung cancer patients will respond favorably to this expensive treatment, let alone cope with its adverse side effects. Despite these issues, this treatment remains the optimal choice for most patients. The effects of radiation and chemotherapy on the immune system have thus far lacked extensive research, especially with regards to how this connects to patient survival. This is what Dr Dirk De Ruysscher and his colleagues wanted to explore further.
They ran a pilot study where they used a multiomics approach to investigate the immune response to radiation and chemotherapy in non-small cell lung cancer (NSCLC) patients.
The pilot study included 45 patients divided into two treatment groups. The first group of patients had stage I NSCLC and received stereotactic body radiation therapy (SBRT), a type of radiation that delivers very precise, intense doses of radiation to cancer cells while avoiding healthy tissue. The second group of patients had stage III NSCLC and were eligible for radiotherapy as well as chemotherapy. Blood was collected at the beginning of therapy, 48 hours (group 1) or 1 week (group 2) into therapy, and at the end of therapy. Dr De Ruysscher used 11 Olink panels analyzing 1000 proteins in plasma samples to investigate treatment effects in these two stages of NSCLC, and whether these effects influence patient survival.
Most interesting were the immune system changes in group 1, which were quite potent and widespread despite the targeted nature of SBRT. The most prominent change in protein expression occurred in proteins associated with NK- and T-cell function, indicative of altered systemic immune responses. This finding was reflected in assays measuring the functional consequences of these proteins on immune cells, which revealed varying levels of general inflammation. There was no correlation between protein expression differences and survival outcome in this group, and this may be because the prognosis in stage I cancer patients is already positive.
There was, however, a difference in protein expression profiles between patients with a longer progression-free survival time (634 days) and those with shorter progression-free survival (324 days) in patients with stage III NSCLC (group 2). When focusing on specific proteins at the root of this difference, Dr De Ruysscher found that IL-17A was especially connected to survival, with low levels of the protein being associated with increased survival in stage 1 patients. There was also a difference in protein expression profiles between stage 1 and stage 3 patients overall.
While only preliminary, these results are promising enough to conduct a larger, future study, which is currently underway. Watch Dr De Ruysscher’s talk below to learn more about how he and his team are helping us accelerate the research in this field using proteomics!