Nam R K, Sugar L, Yang W, Srivastava S, Klotz L H, Yang L-Y, Stanimirovic A, Encioiu E, Neill M, Loblaw D A, Trachtenberg J, Narod S A, Seth A
Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Br J Cancer. 2007 Dec 17;97(12):1690-5. doi: 10.1038/sj.bjc.6604054. Epub 2007 Oct 30.
The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT-PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6-20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.
在大部分人类前列腺癌中，前列腺特异性基因TMPRSS2与转录因子ERG的基因发生融合。TMPRSS2:ERG基因融合产物的存在对预后的意义仍存在争议。我们检查了1998年至2006年间因临床局限性前列腺癌接受手术的165例患者的前列腺癌标本。我们使用逆转录聚合酶链反应（RT-PCR）和直接测序检测TMPRSS2:ERG基因融合产物的存在。我们进行了生存分析，以确定TMPRSS2:ERG融合基因的存在对前列腺癌复发风险的预后意义，并对已确定的预后因素进行了调整。我们发现，165例患者中有81例（49.1%）的前列腺癌细胞中表达了融合基因。在165例患者中，平均随访28个月后，有43例（26.1%）出现前列腺特异性抗原（PSA）复发。融合蛋白阳性的患者亚组复发风险显著高于缺乏融合蛋白的患者（5年时为58.4%对8.1%，P<0.0001）。在多变量分析中，基因融合的存在是最重要的单一预后因素；与无融合蛋白的患者相比，有融合蛋白的患者疾病复发的调整后风险比为8.6（95%可信区间=3.6-20.6，P<0.0001）。在接受手术治疗的前列腺癌患者中，TMPRSS2:ERG融合基因的表达是一个强有力的预后因素，且独立于分级、分期和PSA水平。
