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首页> 外文期刊>BMC Urology >The EEF1A2 gene expression as risk predictor in localized prostate cancer
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The EEF1A2 gene expression as risk predictor in localized prostate cancer

机译：EEF1A2基因表达作为局部前列腺癌的风险预测因子

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Background Besides clinical stage and Gleason score, risk-stratification of prostate cancer in the pretherapeutic setting mainly relies on the serum PSA level. Yet, this is associated with many uncertainties. With regard to therapy decision-making, additional markers are needed to allow an exact risk prediction. Eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was previously suggested as driver of tumor progression and potential biomarker. In the present study its functional and prognostic relevance in prostate cancer was investigated. Methods EEF1A2 expression was analyzed in two cohorts of patients ( n =?40 and n =?59) with localized PCa. Additionally data from two large expression dataset (MSKCC, Cell, 2010 with n =?131 localized, n =?19 metastatic PCa and TCGA provisional data, n =?499) of PCa patients were reanalyzed. The expression of EEF1A2 was correlated with histopathology features and biochemical recurrence (BCR). To evaluate the influence of EEF1A2 on proliferation and migration of metastatic PC3 cells, siRNA interference was used. Statistical significance was tested with t-test, Mann-Whitney-test, Pearson correlation and log-rank test. Results qRT-PCR revealed EEF1A2 to be significantly overexpressed in PCa tissue, with an increase according to tumor stage in one cohort ( p =?0.0443). In silico analyses in the MSKCC cohort confirmed the overexpression of EEF1A2 in localized PCa with high Gleason score ( p =?0.0142) and in metastatic lesions ( p =?0.0038). Patients with EEF1A2 overexpression had a significantly shorter BCR-free survival ( p =?0.0028). EEF1A2 expression was not correlated with serum PSA levels. Similar results were seen in the TCGA cohort, where EEF1A2 overexpression only occurred in tumors with Gleason 7 or higher. Patients with elevated EEF1A2 expression had a significantly shorter BCR-free survival ( p =?0.043). EEF1A2 knockdown significantly impaired the migration, but not the proliferation of metastatic PC3 cells. Conclusion The overexpression of EEF1A2 is a frequent event in localized PCa and is associated with histopathology features and a shorter biochemical recurrence-free survival. Due to its independence from serum PSA levels, EEF1A2 could serve as valuable biomarker in risk-stratification of localized PCa.
机译：背景除临床分期和格里森评分外，治疗前环境中前列腺癌的风险分层主要取决于血清PSA水平。然而，这伴随着许多不确定性。关于治疗决策，还需要其他标记来进行准确的风险预测。以前有人建议将真核翻译延伸因子1 alpha 2（EEF1A2）作为肿瘤进展和潜在生物标志物的驱动力。在本研究中，研究了其在前列腺癌中的功能和预后相关性。方法在两个局部PCa患者（n =？40和n =？59）中分析EEF1A2的表达。另外，还重新分析了来自PCa患者的两个大型表达数据集（MSKCC，Cell，2010，n = 131，n = 19转移性PCa和TCGA临时数据，n = 499）的数据。 EEF1A2的表达与组织病理学特征和生化复发（BCR）相关。为了评估EEF1A2对转移性PC3细胞增殖和迁移的影响，使用了siRNA干扰。统计学显着性用t检验，Mann-Whitney检验，Pearson相关性和对数秩检验进行检验。结果qRT-PCR显示EEF1A2在PCa组织中明显过表达，并且在一个队列中随肿瘤分期而增加（p =？0.0443）。在MSKCC队列中进行的计算机分析表明，EEF1A2在高Gleason评分的局部PCa（p =？0.0142）和转移性病变（p =？0.0038）中过表达。 EEF1A2过表达的患者的无BCR生存期明显缩短（p =？0.0028）。 EEF1A2表达与血清PSA水平无关。在TCGA队列中也观察到了类似的结果，其中EEF1A2过表达仅发生在Gleason 7或更高的肿瘤中。 EEF1A2表达升高的患者的无BCR生存期明显缩短（p =？0.043）。 EEF1A2基因敲低显着损害迁移，但不损害转移性PC3细胞的增殖。结论EEF1A2的过表达是局部PCa中的常见事件，并与组织病理学特征和较短的无生化复发的生存有关。由于它与血清PSA水平无关，因此EEF1A2在局部PCa的风险分层中可以作为有价值的生物标志物。

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