An earlier Olink to Science blog post covered some amazing research that found that certain blood protein biomarkers have the potential to predict cancer up to 3 years before diagnosis. This may also be the case for lung cancer, as detailed in a recent study by Dagnino and her colleagues, where elevated levels of CDCP1 were detected in participants of a cohort who later developed the disease.
Chronic inflammation is a risk factor for the development of certain cancers, and cancer itself can also induce local inflammation, leading to tumor growth and metastasis. This inflammation can be seen as changes in the levels of cytokines and other proteins in the blood, and as such, these markers could make for ideal indicators of early cancer development. Past research has, however, only investigated a limited number of inflammatory markers or has been limited to analysis of plasma from participants with a short time to diagnosis.
Dagnino and colleagues sought to expand their analysis to a larger number of assays, as well as monitor participants for a longer period (16 years) to determine whether any inflammatory markers were already elevated more than 5 years before cancer diagnosis. The study used the Olink inflammation panel to analyze 92 proteins in 650 participants from 2 cohorts, the European Prospective Investigation into Cancer (EPIC), and the Norwegian Women and Cancer Study (NOWAC).
Initial analysis revealed 12 proteins that were associated with increased risk of lung cancer in women, but most were not statistically significant when analyses were adjusted for smoking. More interestingly, elevated CDCP1 was also statistically significant in women who never smoked, as well as in both smoking and non-smoking men. Elevated levels of CDCP1 could be detected over 5 years before cancer diagnosis.
The study sought to further elucidate the connection between CDCP1 and lung cancer risk by combining proteomic results with gene expression data. Correlation between blood levels of CDCP1 and levels of over 11610 gene transcripts suggested a significant association between CDCP1 and the expression of LRRN3 and SEM1. LRRN3 has been associated with smoking exposure in past research, which indicates that CDCP1 may play a role in smoking-induced lung cancer-related biological pathways. The analysis also suggested a strong association between CDCP1 and the WNT/B-catenin activation pathway, which has been linked to a wide variety of other cancers by activating genes involved in tumor development.
The results of this study suggest that CDCP1 may serve as an early indicator of lung cancer risk irrespective of smoking history. Moreover, the association between CDCP1 and lung cancer risk gives further indications of the biological mechanisms and pathways at play years before the disease manifests, further emphasizing the value of multiomics analysis. These last 4 blog posts have shown just how integral proteomics is to the progress of cancer research, and we at Olink are excited to see how much more we may contribute to this research space.
Dagnino et al. 2021, Prospective identification of elevated circulating CDCP1 in patients years before onset of lung cancer, Cancer Res. DOI: 10.1158/0008-5472.CAN-20-3454