Burger Michelle Jane, Tebay Michelle Anne, Keith Patricia Anne, Samaratunga Hema Mali, Clements Judith, Lavin Martin Francis, Gardiner Robert Alexander
Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Brisbane, Australia.
Int J Cancer. 2002 Jul 10;100(2):228-37. doi: 10.1002/ijc.10468.
The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and 1 BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for delta-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer.
当前前列腺癌的诊断方法存在重大局限性,包括前列腺特异性抗原(PSA)检测无法准确区分前列腺癌和良性前列腺增生(BPH),以及经直肠超声(TRUS)活检采样的不精确性。我们采用cDNA微阵列筛选来比较BPH和肿瘤样本中的基因表达模式,以识别可能有助于区分这些病症的表达标志物。对3个单独的cDNA阵列进行筛选,在6个肿瘤组织中鉴定出8个基因,其表达水平比1个非肿瘤样本和1个BPH样本高3倍。使用实时PCR来确认这8个基因以及从文献中选取的12个基因在一组17个肿瘤样本和11个BPH样本中的过表达情况。与BPH相比,δ-连环蛋白(δ-catenin;CTNND2)和前列腺特异性膜抗原(PSMA;FOLH1)这两个基因在前列腺癌中显著过表达。在我们的前列腺癌组织中,前列腺上皮细胞δ-连环蛋白和PSMA染色呈阳性,而我们的大多数BPH组织这两种标志物均为阴性。因此,我们鉴定出了δ-连环蛋白(之前未与前列腺腺癌相关联),并证实了PSMA作为前列腺癌诊断和治疗潜在候选标志物的潜力。