Accurate detection of characteristic proteins secreted by colon cancer tumor cells in biological fluids could serve as a biomarker for the disease. The aim of the present study was to identify and validate new serum biomarkers and demonstrate their potential usefulness for early diagnosis of colon cancer.
Methods
The study was organized in three sequential phases: 1) biomarker discovery, 2) technical and biological validation, and 3) proof of concept to test the potential clinical use of selected biomarkers. A prioritized subset of the differentially-expressed genes between tissue types (50 colon mucosa from cancer-free individuals and 100 normal-tumor pairs from colon cancer patients) was validated and further tested in a series of serum samples from 80 colon cancer cases, 23 patients with adenoma and 77 cancer-free controls.
Results
In the discovery phase, 505 unique candidate biomarkers were identified, with highly significant results and high capacity to discriminate between the different tissue types. After a subsequent prioritization, all tested genes (N = 23) were successfully validated in tissue, and one of them, COL10A1, showed relevant differences in serum protein levels between controls, patients with adenoma (p = 0.0083) and colon cancer cases (p = 3.2e-6).
Conclusion
We present a sequential process for the identification and further validation of biomarkers for early detection of colon cancer that identifies COL10A1 protein levels in serum as a potential diagnostic candidate to detect both adenoma lesions and tumor.
Impact
The use of a cheap serum test for colon cancer screening should improve its participation rates and contribute to decrease the burden of this disease. 相似文献
We reconsider the deterministic haploid mutation–selection equation with two types. This is an ordinary differential equation that describes the type distribution (forward in time) in a population of infinite size. This paper establishes ancestral (random) structures inherent in this deterministic model. In a first step, we obtain a representation of the deterministic equation’s solution (and, in particular, of its equilibria) in terms of an ancestral process called the killed ancestral selection graph. This representation allows one to understand the bifurcations related to the error threshold phenomenon from a genealogical point of view. Next, we characterise the ancestral type distribution by means of the pruned lookdown ancestral selection graph and study its properties at equilibrium. We also provide an alternative characterisation in terms of a piecewise-deterministic Markov process. Throughout, emphasis is on the underlying dualities as well as on explicit results.
Four decades ago, it was proposed that environmental sex determination (ESD) evolves when individual fitness depends on the environment in a sex‐specific fashion—a form of condition‐dependent sex allocation. Many biological processes have been hypothesized to drive this sex asymmetry, yet a general explanation for the evolution of sex‐determining mechanisms remains elusive. Here, we develop a mathematical model for a novel hypothesis of the evolution of ESD, and provide a first empirical test using data across turtles. ESD is favored when the sex‐determining environment affects annual survival rates equivalently in males and females, and males and females mature at different ages. We compare this hypothesis to alternative hypotheses, and demonstrate how it captures a crucially different process. This maturation process arises naturally from common life histories and applies more broadly to condition‐dependent sex allocation. Therefore, it has widespread implications for animal taxa. Across turtle species, ESD is associated with greater sex differences in the age at maturity compared to species without ESD, as predicted by our hypothesis. However, the effect is not statistically significant and will require expanded empirical investigation. Given variation among taxa in sex‐specific age at maturity, our survival‐to‐maturity hypothesis may capture common selective forces on sex‐determining mechanisms. 相似文献