Dhanasekaran S M, Barrette T R, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta K J, Rubin M A, Chinnaiyan A M
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nature. 2001 Aug 23;412(6849):822-6. doi: 10.1038/35090585.
Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer. Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.
前列腺癌是美国男性中最常被诊断出的癌症。前列腺特异性抗原（PSA）筛查已使前列腺癌得以更早发现，但血清PSA水平升高也可能出现在诸如良性前列腺增生（BPH）等非恶性疾病中。对在分子水平上区分前列腺肿瘤的基因表达谱进行特征分析，可能会鉴定出参与前列腺癌发生的基因，阐明临床生物标志物，并改进前列腺癌的分类。我们使用互补DNA微阵列，检测了50多个正常和肿瘤性前列腺标本以及三种常见前列腺癌细胞系的基因表达谱。确定了正常相邻前列腺（NAP）、BPH、局限性前列腺癌以及转移性、激素难治性前列腺癌的特征性表达谱。在此我们建立了许多基因与前列腺癌之间的关联。我们使用由700多个临床分层的前列腺癌标本组成的组织微阵列，在蛋白质水平评估了其中两个基因——跨膜丝氨酸蛋白酶海普辛和丝氨酸/苏氨酸激酶pim-1。海普辛和pim-1蛋白的表达与临床结局指标显著相关。因此，cDNA微阵列、高密度组织微阵列以及相关临床和病理数据的整合是一种对人类癌症进行分子分析的有力方法。
