A PhD student from Stellenbosch University has established that the early detection of colorectal cancer risk would be greatly enhanced by a holistic approach that takes into account the complex interplay between chronic inflammation, abnormal blood clotting and the involvement of a bacterial presence.
Colorectal cancer, also known as colon cancer, is currently the third most diagnosed cancer in the world. When diagnosed early, about 90% of the patients will have a five-year life expectancy. It reduces to 13% with a late or delayed diagnosis.
Dr Greta de Waal, who received her doctoral degree during the Faculty of Science's SU's graduation ceremony on 1 April 2021, emphasises that colorectal cancer is a multifactorial and heterogeneous cancer, with various contributors and drivers involved in its pathogenesis: “Most cases of colorectal cancer encompass a variety of contributing risk factors, in addition to genetic features. Because of the heterogeneity of the disease, it is crucial to employ holistic approaches to determine how all the different factors involved in the carcinogenic process are linked to (and may fuel) each other," she explains.
In her research, she analysed and described both the systemic environment and local tumour environment of patients with colorectal cancer. She developed and optimised a novel fluorescence antibody-based technique to detect the bacterial inflammagen, lipopolysaccharide (LPS), in blood. She was then able to show that the circulating levels of this bacterial wall component are significantly elevated in patients with colorectal cancer, compared to healthy individuals. In addition, she also demonstrated an intratumour bacterial presence in these patients. She thus found that the presence of a bacterial component forms a key part of the overall profile of patients with colorectal cancer, with systemic inflammation and increased hypercoagulability also being central.
Dr De Waal says there is an intricate relationship between a dysfunctional gut microbiome and a pro-inflammatory profile in these patients: “Alterations in the composition of the gut microbiota can contribute to the development of a dysfunctional gut barrier, thereby facilitating the translocation of bacteria and their inflammagenic molecules. Such leaky gut conditions can promote systemic inflammation, of which a hallmark is abnormal blood clotting".
Chronic inflammation and hypercoagulation are both implicated in the formation of tumours. The researchers believe these conditions – elevated presence of certain circulating bacterial and other inflammatory markers, and the incidence of abnormal blood clotting – could be used as biomarkers in blood-based screening tools when screening patients for colorectal cancer risk.
“All of this information can be obtained by taking a simple blood sample, and then knowing what to look for," adds Prof Resia Pretorius, her supervisor and a physiologist in the Department of Physiological Sciences at SU.
Prof Pretorius says the work is the result of a fruitful collaboration between herself and clinicians from SU's Faculty of Medicine and Health Sciences at Tygerberg, with the SU rector Prof Wim de Villiers, who is a gastroenterologist himself, acting as co-supervisor.
“While we benefited from Prof De Villiers' expertise of the clinical side of colorectal cancer and its treatment, we could add our expertise of what is happening at the molecular level," she explains.
Prof Resia Pretorius
Head: Department of Physiological Sciences, SU
Dr Greta de Waal
Postdoctoral Fellow, Department of Physiological Sciences, SU
On the photo, Dr Greta de Waal (middle), together with her study leaders Prof Resia Pretorius and Prof Wim de Villiers, after the 1 April 2021 graduation ceremony. Photo: Stefan Els