Schroeder Cornelia, Navid-Hill Elham, Meiners Jan, Hube-Magg Claudia, Kluth Martina, Makrypidi-Fraune Georgia, Simon Ronald, Büscheck Franziska, Luebke Andreas M, Goebel Cosima, Lang Dagmar S, Weidemann Sören, Neubauer Emily, Hinsch Andrea, Jacobsen Frank, Lebok Patrick, Michl Uwe, Pehrke Dirk, Huland Hartwig, Graefen Markus, Schlomm Thorsten, Sauter Guido, Höflmayer Doris
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Oncotarget. 2019 Aug 13;10(48):4973-4986. doi: 10.18632/oncotarget.27132.
ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of :ERG fusion, higher Ki67-labeling index and deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64-2.10, < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11-1.49, = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse.
ELAC2是一种普遍表达的酶，可能参与tRNA加工和细胞信号通路。已发现ELAC2基因突变会增加家族性前列腺癌易感性。通过免疫组织化学分析了9262例患者的ELAC2蛋白表达，并计算了8513例接受根治性前列腺切除术患者的PSA无复发生存期的Kaplan-Meier曲线。在60.8%的前列腺癌中观察到核ELAC2染色。染色弱的占26.3%，中等强度的占26.6%，强染色的占7.9%。核ELAC2强表达与肿瘤晚期、淋巴结转移、更高的Gleason分级、ERG融合的存在、更高的Ki67标记指数和缺失相关。在所有癌症中，核ELAC2强度强与弱的1年、5年和10年无复发生存率差异分别为7.2%/13.8%/17.6%，在ERG阴性亚组中为7.4%/16.1%/26.5%，在ERG阳性亚组中为3.1%/5.7%/9.8%。关于单变量风险比，核ELAC2强表达的前列腺切除术后PSA无复发生存率为1.89(1.64 - 2.10，P < 0.0001)。它独立于术前PSA水平、Gleason分级、病理分期、手术切缘分期和淋巴结分期(多变量风险比1.29(1.11 - 1.49，P = 0.001)。我们得出结论，核ELAC2表达是根治性前列腺切除术后PSA无复发生存率的独立预后标志物，生化复发风险比有轻度至中度增加。
