O'Malley Jordan, Kumar Rahul, Kuzmin Andrey N, Pliss Artem, Yadav Neelu, Balachandar Srimmitha, Wang Jianmin, Attwood Kristopher, Prasad Paras N, Chandra Dhyan
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Cancer Lett. 2017 Jul 1;397:52-60. doi: 10.1016/j.canlet.2017.03.025. Epub 2017 Mar 23.
Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort. Increased lipid accumulation in late-stage transgenic adenocarcinoma of mouse prostate (TRAMP) tumors compared to early-stage TRAMP and normal prostate tissues were observed. FASN along with other lipogenesis enzymes, and SREBP-1 proteins were upregulated in TRAMP tumors compared to wild-type prostatic tissues. Genetic alterations of key lipogenic genes predicted the overall patient survival using TCGA PRAD cohort. Correlation between lipid accumulation and tumor stage provides quantitative marker for PCa diagnosis. Thus, Raman spectroscopy-based lipid quantification could be a sensitive and reliable tool for PCa diagnosis and staging.
转移性去势抵抗性前列腺癌(mCRPC)仍然无法治愈,是美国男性癌症相关死亡的主要原因之一。因此,早期检测前列腺癌(PCa)可能会降低男性PCa相关死亡率。我们表明,通过振动拉曼光谱和生物分子成分分析进行脂质定量可能作为PCa的潜在生物标志物。在PRAD TCGA队列中,包括固醇调节元件结合蛋白-1(SREBP-1)及其下游效应物脂肪酸合酶(FASN)以及限速酶乙酰辅酶A羧化酶(ACACA)在内的生脂基因的转录水平与Gleason评分和病理T分期均呈上调。与早期TRAMP和正常前列腺组织相比,在晚期小鼠前列腺转基因腺癌(TRAMP)肿瘤中观察到脂质积累增加。与野生型前列腺组织相比,TRAMP肿瘤中FASN以及其他脂肪生成酶和SREBP-1蛋白上调。使用TCGA PRAD队列,关键生脂基因的基因改变可预测患者的总体生存率。脂质积累与肿瘤分期之间的相关性为PCa诊断提供了定量标志物。因此,基于拉曼光谱的脂质定量可能是用于PCa诊断和分期的灵敏且可靠的工具。