Colorectal cancer is associated with increased circulating lipopolysaccharide, inflammation and hypercoagulability

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Our research group consists of physiologists, a gastroenterologist, a colorectal surgeon, as well as a data scientist who are all interested in making a difference in patients’ lives, and also to pursue novel applications for our research findings. Novel strategies must be used to aid in the identification of individuals at risk of developing colorectal cancer (CRC). Importantly, blood-based screening tools are an emerging research area of interest for CRC screening.

One of us, Willem de Villiers, is a gastroenterologist and an expert in Inflammatory Bowel Disease. He has often noticed in the clinical setting that patients who experience flares of their chronic intestinal inflammation or who suffer from CRC also are more likely to have complications such as venous thrombosis (hypercoagulability). This paper investigated the presence of circulating lipopolysaccharide (LPS) and other circulating biomarkers, indicative of systemic inflammation and abnormal clot formation, in healthy individuals and patients with newly diagnosed CRC.

We showed that circulating levels of LPS are significantly elevated in the CRC population. Moreover, markers of inflammation and hypercoagulability are also increased in this population. Statistical regression models identified markers with strong association with CRC, and we investigated the correlation between these markers. A core aim of our study was therefore biomarker discovery for CRC across a wide range of groups (see Figure 1).

Figure 1. Elevated levels of circulating lipopolysaccharide (LPS) and markers of inflammation and hypercoagulability are associated with colorectal cancer (CRC), presenting novel blood-based screening approaches. Figure made in ©BioRender - https://biorender.com/.

We concluded that CRC patients have a dysregulated inflammatory biomarker profile, which manifests in multiple pathological hematological changes. We observed significant correlations between circulating LPS levels and blood clot parameters, suggesting that a link exists between a bacterial presence and hematological pathology, ultimately resulting in abnormal clot formation. This study therefore placed new emphasis on, and revealed the intricate relationship between a bacterial influence, persistent inflammation, hypercoagulation, and colorectal carcinogenesis (refer to Figure 2 for a summary of our results). The wider relevance of our research is in the identification of (novel) biomarkers of multiple groups (inflammatory markers, vascular damage markers, and circulating LPS), that are associated with CRC, presenting an opportunity for improved CRC blood-based screening.
Figure 2. Summary of the results of the paper, highlighting circulating lipopolysaccharide (LPS) as one of the main factors promoting systemic inflammation and hematological dysfunction in colorectal cancer (CRC) patients. Figure made in ©BioRender - https://biorender.com/.

Greta de Waal

PhD student, Stellenbosch University

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