最新一期Nature刊发了一篇前列腺癌最新分子标记的文章，该研究成果为快速检测前列腺癌提供了新线索。
一直以来，临床肿瘤医生们在前列腺癌的诊治过程中备受打击，他们往往能轻易地诊断出前列腺癌患者，却无法诊断出该患者是恶性前列腺癌还是良性前列腺癌，这往往导致恶性前列腺癌患者丧失了最佳治疗的机会。而美国密歇根大学这项新的研究成果有助临床肿瘤医生走出这个困境。
这一项目是密歇根大学，霍华休斯医学院的研究者最新的研究成果。研究者对前列腺癌样品中的代谢物所做的一项系统分析，他们发现一个问题：肌氨酸（包括肌肉在内的很多生物组织中的一种常见氨基酸）在侵略性前列腺癌中含量显著升高。
值得关注的是，肌氨酸在男性前列腺癌患者的尿样中可检测出来。这一发现使得肌氨酸成为前列腺癌诊断的一个候选生物标记。
更令人振奋的是，用遗传技术将甘氨酸生成肌氨酸的酶定向剔除，小鼠动物实验发现，剔除了生成肌氨酸的酶将大大降低前列腺癌的恶性程度，这说明肌氨酸在癌细胞转移中可能扮演重要角色，因此肌氨酸通道可能成为前列腺癌的新治疗靶位。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 457, 910-914 (12 February 2009) | doi:10.1038/nature07762
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Arun Sreekumar1,2,3,4, Laila M. Poisson5,13, Thekkelnaycke M. Rajendiran1,3,13, Amjad P. Khan1,3,13, Qi Cao1,3, Jindan Yu1,3, Bharathi Laxman1,3, Rohit Mehra1,3, Robert J. Lonigro1,4, Yong Li1,3, Mukesh K. Nyati4,6, Aarif Ahsan6, Shanker Kalyana-Sundaram1,3, Bo Han1,3, Xuhong Cao1,3, Jaeman Byun7, Gilbert S. Omenn2,7,8, Debashis Ghosh4,5,11, Subramaniam Pennathur2,4,7, Danny C. Alexander12, Alvin Berger12, Jeffrey R. Shuster12, John T. Wei4,9, Sooryanarayana Varambally1,3,4, Christopher Beecher1,2,3 & Arul M. Chinnaiyan1,2,3,4,9,10
1 The Michigan Center for Translational Pathology,
2 Center for Computational Medicine and Biology,
3 Department of Pathology,
4 The Comprehensive Cancer Center,
5 Department of Biostatistics,
6 Department of Radiation Oncology,
7 Department of Internal Medicine,
8 Department of Human Genetics,
9 Department of Urology,
10 Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
11 Department of Statistics and Huck Institute of Life Sciences, Penn State University, Pennsylvania 16802, USA
12 Metabolon, Inc. 800 Capitola Drive, Suite 1 Durham, North Carolina 27713, USA
13 These authors contributed equally to this work.
Multiple, complex molecular events characterize cancer development and progression1, 2. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.
