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循环中的天冬氨酸水平降低是人类乳腺癌的一种代谢特征。

Lowered circulating aspartate is a metabolic feature of human breast cancer.

作者信息

Xie Guoxiang, Zhou Bingsen, Zhao Aihua, Qiu Yunping, Zhao Xueqing, Garmire Lana, Shvetsov Yurii B, Yu Herbert, Yen Yun, Jia Wei

机构信息

Center for Translational Medicine, and Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

University of Hawaii Cancer Center, Honolulu, HI, USA.

出版信息

Oncotarget. 2015 Oct 20;6(32):33369-81. doi: 10.18632/oncotarget.5409.

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.

摘要

独特的代谢转变对于癌细胞维持高增殖率和抵抗细胞死亡信号至关重要。这种代谢转变会导致独特的细胞代谢表型,这通常通过肿瘤组织以及循环血液中独特的代谢物特征反映出来。利用代谢组学平台,我们发现,在一个由35名乳腺癌患者和35名对照组成的训练组中,乳腺癌与血浆天冬氨酸水平显著降低(p = 6.27E - 13)相关。该结果在两组原发性乳腺癌患者的103份血浆样本和183份血清样本中得到验证。这种降低的天冬氨酸水平是乳腺癌所特有的,因为它在胃癌(n = 114)和结直肠癌(n = 101)患者的血清中敏感性为0%。乳腺癌组织(n = 20)中的天冬氨酸水平显著高于相邻的非肿瘤组织,在MCF - 7乳腺癌细胞系中的天冬氨酸水平高于MCF - 10A细胞系,这表明乳腺癌患者血液中天冬氨酸水平的降低是由于肿瘤对天冬氨酸的利用增加。总之,这些发现表明循环天冬氨酸水平降低是人类乳腺癌的一个关键代谢特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2767/4741772/08a41b2754d4/oncotarget-06-33369-g001.jpg

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