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Abstract
Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer.
Highlights
Breast cancer remains to be one of the most commonly diagnosed and death-related cancers in women in the United States, resulting in an estimated 40,730 new deaths in 2015 [1,2,3]
While genetic alterations have been extensively characterized in breast cancer, the changes in metabolism that occur downstream from genomic and proteomic alterations have not been characterized in detail to date
Since blood is in contact with virtually all tissues in the human body and is considered to reflect in a dynamic way the pathophysiological status, serum/plasma metabolomic changes are of particular importance with diagnostic value for early cancer detection [21]
Summary
Breast cancer remains to be one of the most commonly diagnosed and death-related cancers in women in the United States, resulting in an estimated 40,730 new deaths in 2015 [1,2,3]. Recent metabolomic studies of breast cancer have provided important metabolic signatures in serum, plasma [14,15,16,17], and tissue [18] that differentiate breast cancer from healthy controls.
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