Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer -what has gone wrong? A blueprint for the way forward in biomarker studies.

Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer -what has gone wrong? A blueprint for the way forward in biomarker studies.
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DOI:
10.1038/bjc.2014.588
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发表时间:
2015-01-06
影响因子:
8.8
通讯作者:
Kristiansen, G.
Kristiansen, G.
中科院分区:
医学1区
文献类型:
--
作者:
Huber, F.;Montani, M.;Sulser, T.;Jaggi, R.;Wild, P.;Moch, H.;Gevensleben, H.;Schmid, M.;Wyder, S.;Kristiansen, G.

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局限性前列腺癌的治疗计划仍然具有挑战性。除了常规参数外,迄今为止已经提出了大量的预后生物标志物。然而,迄今为止,没有一项在日常环境中得到成功实施。本研究的目的是系统地验证一组已发表的前列腺癌预后标志物。在深入的PubMed检索后,选择了28个标记物,这些标记物已被提议作为原发性前列腺癌的多变量预后标记物。在238例根治性直肠癌切除术患者队列中检查其预后有效性,中位随访时间为60个月,生化进展作为分析终点。使用先前发表的临界值进行免疫组织化学评价,但必要时允许优化。单变量和多变量考克斯回归用于确定本研究中包括的生物标志物的预后价值。尽管在分析中应用了各种截止值,但只有四种(14%)标志物被证实为根治性前列腺切除术后PSA复发的独立预后(AKT1,基质AR,EZH2和PSMA)。显然,许多基于生物化学的预后标志物研究似乎过于乐观。最佳做法守则,如REMARK准则,可促进今后开展结论性和透明的研究。
Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.
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