Göbel Cosima, Özden Cansu, Schroeder Cornelia, Hube-Magg Claudia, Kluth Martina, Möller-Koop Christina, Neubauer Emily, Hinsch Andrea, Jacobsen Frank, Simon Ronald, Sauter Guido, Michl Uwe, Pehrke Dirk, Huland Hartwig, Graefen Markus, Schlomm Thorsten, Luebke Andreas M
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.
Cancer Manag Res. 2018 Nov 9;10:5491-5504. doi: 10.2147/CMAR.S165630. eCollection 2018.
Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer.
Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival.
CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene () fusion as well as phosphatase and tensin homolog deletion (<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses.
The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.
着丝粒蛋白F（CENPF）是动粒复合体的关键组成部分，在染色体分离和细胞周期进程中发挥着至关重要的作用。近期研究表明，CENPF的上调与包括前列腺癌在内的多种恶性肿瘤的侵袭性肿瘤特征有关。
我们使用高度注释的组织微阵列，通过免疫组织化学分析了8298例接受前列腺切除术患者队列中的CENPF蛋白表达，以研究其对无前列腺特异性抗原复发生存的影响。
在53%的癌症中发现CENPF过表达，且与更高的Gleason分级、晚期病理肿瘤分期、加速的细胞增殖和淋巴结转移相关（每项均<0.0001）。与通过微阵列可获得的其他关键分子特征进行比较发现，CENPF过表达与成红细胞转化特异性（ETS）相关基因（）融合以及磷酸酶和张力蛋白同源物缺失的存在之间存在强关联（每项均<0.0001）。CENPF过表达与早期生化复发相关。亚组分析显示，这是由ERG阴性亚组驱动的（<0.0001）。在多变量分析中，这与既定的术前和术后预后参数无关。
我们的研究结果确定CENPF过表达是前列腺癌侵袭性的重要机制和潜在生物标志物。
