Abstract
BackgroundCancer is a genetic disease; its development and metastasis depend on the function of many proteins. Human serum contains thousands of proteins; it is a window for the homeostasis of individual’s health. Many of the proteins found in the human serum could be potential biomarkers for cancer early detection and drug efficacy evaluation.MethodsIn this study, a functional proteomics technology was used to systematically monitor metabolic enzyme and protease activities from resolved serum proteins produced by a modified 2-D gel separation and subsequent Protein Elution Plate, a method collectively called PEP. All the experiments were repeated at least twice to ensure the validity of the findings.ResultsFor the first time, significant differences were found between breast cancer patient serum and normal serum in two families of enzymes known to be involved in cancer development and metastasis: metabolic enzymes and proteases. Multiple enzyme species were identified in the serum assayed directly or after enrichment. Both qualitative and quantitative differences in the metabolic enzyme and protease activity were detected between breast cancer patient and control group, providing excellent biomarker candidates for breast cancer diagnosis and drug development.ConclusionsThis study identified several potential functional protein biomarkers from breast cancer patient serum. It also demonstrated that the functional proteomics technology, PEP, can be applied to the analysis of any functional proteins in human serum which contains thousands of proteins. The study indicated that the functional domain of the human serum could be unlocked with the PEP technology, pointing to a novel alternative for the development of diagnosis biomarkers for breast cancer and other diseases.
Highlights
Cancer is a genetic disease; its development and metastasis depend on the function of many proteins
Comparison of hexokinase activity from normal serum and breast cancer patient serum Previous effort in proteomics has identified thousands of proteins from human serum, a high percentage of the proteins identified are enzymes with significant numbers belongs to metabolic enzymes and proteases
There have been many reports of single or multiple protein panels as potential biomarkers for breast cancer diagnosis, so far there are no routinely used serum-based biomarkers approved for breast cancer [1]
Summary
Cancer is a genetic disease; its development and metastasis depend on the function of many proteins. Many of the proteins found in the human serum could be potential biomarkers for cancer early detection and drug efficacy evaluation. Human breast cancer is a major cause of morbidity and mortality in women. The highest incidence rates were found in the United States and Western Europe with 101 and 85 new cases per 100.000 women, respectively [1]. The. American Cancer Society estimates that each year more than 230,000 Americans women will be diagnosed with this neoplasia and that more than 40,000 will die of the disease in the United States. Presymptomatic screening to detect early-stage cancer while it is still resectable with potential for cure can significantly reduce breast cancerrelated mortality. One reason that contributes to the poor prognosis of patients diagnosed with breast cancer is the fact that the diagnosis is often delayed due to limitations in mammography.
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