TOPLINE:
In patients with newly diagnosed type 2 diabetes (T2D), elevated YKL-40 (chitinase-3–like protein 1) levels were strongly linked to an increased risk for liver cancer and, to a lesser extent, bladder cancer, highlighting the potential of YKL-40 as a biomarker for obesity-related and gastrointestinal cancers.
METHODOLOGY:
- YKL-40 is an inflammatory biomarker linked to tumour progression in various cancers, and its levels are consistently elevated in patients with T2D, a condition linked to increased risks for multiple cancers.
- Researchers examined the association of YKL-40 with cancers related to obesity and T2D and compared its prognostic performance with that of C-reactive protein (CRP) in a cohort of patients newly diagnosed with T2D in Denmark from 2010 to 2023.
- They analysed 11,346 patients newly diagnosed with T2D, of whom 9010 and 9644 patients were analysed for the measurement of YKL-40 and CRP biomarker levels, respectively, with a median follow-up duration of 4-5 years for cases with cancers; demographic information was gathered from enrolment interviews and clinical examinations or through linkage with the national diabetes registry.
- YKL-40 levels were determined using an enzyme-linked immunosorbent assay and were categorised into percentiles, and participants were then grouped on the basis of their YKL-40 percentile categories, from lowest to highest.
- The primary analysis focused on cancers associated with obesity and T2D, including liver, pancreatic, colorectal, bladder, lung, breast, ovarian, and prostate cancers.
TAKEAWAY:
- Elevated YKL-40 levels were linked to longer diabetes duration; higher body mass index; alcohol overconsumption; smoking; lower physical activity, insulin sensitivity, and kidney function; and higher A1c, triglyceride, and CRP levels.
- Moreover, elevated YKL-40 levels were associated with a significantly increased risk for liver cancer (adjusted hazard ratio [aHR], 44.2; 95% CI, 12.8-153.4).
- A significant association was observed between elevated YKL-40 levels and increased risks for obesity-related cancers (aHR, 2.4; 95% CI, 1.6-3.7), gastrointestinal cancers (aHR, 2.6; 95% CI, 1.7-4.1), and bladder cancer (aHR, 4.2; 95% CI, 1.3-14.1). No associations were found for other types of cancer.
- YKL-40 showed a stronger prognostic ability than CRP for liver and bladder cancers, whereas CRP demonstrated superior prognostic ability for lung, colorectal, and ovarian cancers.
IN PRACTICE:
"YKL-40, in particular, shows strong precision medicine potential as a biomarker for liver cancer, supporting its use in early detection and focused monitoring in this population," the authors wrote.
SOURCE:
This study was led by Alisa D. Kjaergaard, Aarhus University Hospital, Aarhus, Denmark. It was published online on April 05, 2025, in the British Journal of Cancer.
LIMITATIONS:
This study was limited by potential survival and selection bias, which may have led to an underrepresentation of individuals with severe T2D or a high risk for cancer. The use of registry-based diagnoses may have introduced misclassification, potentially underestimating the true association. Additionally, participants who developed cancer shortly after enrolment were not excluded, which may have introduced bias through reverse causation.
DISCLOSURES:
This study was funded by a Steno National Collaborative Grant, and the national cohort was supported by the Danish Agency for Science and Education, the Danish Health and Medicines Authority, the Danish Diabetes Association, and unrestricted donation from Novo Nordisk A/S. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
