最新一期Nature刊發(fā)了一篇前列腺癌最新分子標(biāo)記的文章,，該研究成果為快速檢測(cè)前列腺癌提供了新線索,。
一直以來(lái),，臨床腫瘤醫(yī)生們?cè)谇傲邢侔┑脑\治過(guò)程中備受打擊,，他們往往能輕易地診斷出前列腺癌患者,，卻無(wú)法診斷出該患者是惡性前列腺癌還是良性前列腺癌，這往往導(dǎo)致惡性前列腺癌患者喪失了最佳治療的機(jī)會(huì),。而美國(guó)密歇根大學(xué)這項(xiàng)新的研究成果有助臨床腫瘤醫(yī)生走出這個(gè)困境,。
這一項(xiàng)目是密歇根大學(xué)，霍華休斯醫(yī)學(xué)院的研究者最新的研究成果,。研究者對(duì)前列腺癌樣品中的代謝物所做的一項(xiàng)系統(tǒng)分析,，他們發(fā)現(xiàn)一個(gè)問(wèn)題：肌氨酸（包括肌肉在內(nèi)的很多生物組織中的一種常見(jiàn)氨基酸）在侵略性前列腺癌中含量顯著升高。
值得關(guān)注的是,，肌氨酸在男性前列腺癌患者的尿樣中可檢測(cè)出來(lái)。這一發(fā)現(xiàn)使得肌氨酸成為前列腺癌診斷的一個(gè)候選生物標(biāo)記,。
更令人振奮的是,，用遺傳技術(shù)將甘氨酸生成肌氨酸的酶定向剔除，小鼠動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，剔除了生成肌氨酸的酶將大大降低前列腺癌的惡性程度,，這說(shuō)明肌氨酸在癌細(xì)胞轉(zhuǎn)移中可能扮演重要角色,，因此肌氨酸通道可能成為前列腺癌的新治療靶位。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
