A test is needed that offers greater certainty and that can detect bowel cancer at an early stage and at the same time reaches the whole population. Should this be achieved with a blood test, it might lower the reluctance seen in patients towards the stool test.
From the moment that colorectal cancer cells are present in the body, the peripheral blood monocytes respond to the substances secreted by the cancer cells, and the immune system responds to this and tries to remove the cancer cells from the body. A specific role in this process is assigned to a specific type of white blood cell, the peripheral blood monocyte.
A large group Europeans scientists led by those at the Vesalius Research Center (VIB; Leuven, Belgium) used peripheral blood monocytes in order to characterize a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. They performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centers and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting.
The investigators found 43 putative diagnostic markers, which were refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy. The diagnostic accuracy was robustly maintained in prospectively collected independent samples with a sensitivity of 92.6% and a specificity of 92.3%. This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes.
The expression changes were plastic and reversible, as they were abrogated upon withdrawal of tumor-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. The authors concluded that they are the first to demonstrate monocyte plasticity in response to tumor-released soluble factors. The identified distinct signature in tumor-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbors the potential for disease follow-up and therapeutic monitoring.
Massimiliano Mazzone, PhD, a professor and senior author of the study, said, “This study demonstrates how important it is to gain a thorough understanding of the role of our immune system in cancer. In this case, this knowledge will hopefully result in a new, more sensitive test to detect colorectal cancer at an early stage, so that more patients can be cured. I hope that we can soon find an industrial partner to help us achieve the following step, which is the development of the test.” The study was published on March 25, 2015, in the journal Gut.
Vesalius Research Center