Rödel Franz, Zhou Shengtao, Győrffy Balász, Raab Monika, Sanhaji Mourad, Mandal Ranadip, Martin Daniel, Becker Sven, Strebhardt Klaus
Department of Radiotherapy and Oncology, University Hospital, Goethe-University, Frankfurt am Main, Germany.
Frankfurt Cancer Institute, Goethe-University, Frankfurt am Main, Germany.
Front Oncol. 2020 Oct 7;10:558932. doi: 10.3389/fonc.2020.558932. eCollection 2020.
Since type and duration of an appropriate adjuvant chemotherapy in early-stage ovarian cancer (OC) are still being debated, novel markers for a better stratification of these patients are of utmost importance for the design of an improved chemotherapeutical strategy. In contrast to numerous cancer studies on cellular proliferation based on the immunohistochemistry-driven evaluation of protein expression, we compared mRNA and protein expression of two independent markers of cellular proliferation, Ki-67 and Plk1, in a large cohort of 243 early-stage OC and their relationship with clinicopathological features and survival. Based on marker expression we demonstrate that early-stage OC patients (stages I/II, low-grade, serous) with high expression (Ki-67, Plk1) had a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to patients with low expression (Ki-67, Plk1). Remarkably, based on mRNA expression this significant difference got lost in advanced stages (III/IV): At least for PFS, high levels of Ki-67 and Plk1 correlate with moderately better survival compared to patients with low expressing tumors. Our data suggest that in addition to Ki-67, Plk1 is a novel marker for the stratification of early-stage OC patients to maximize therapeutic efforts. Both, Ki-67 and Plk1, seem to be better suited in early-stages (I/II) as therapeutical targets compared to advanced-stages (III/IV) OC.
由于早期卵巢癌(OC)合适的辅助化疗类型和持续时间仍存在争议,对于这些患者进行更好分层的新型标志物对于设计改进的化疗策略至关重要。与众多基于免疫组化驱动的蛋白质表达评估进行细胞增殖的癌症研究不同,我们在243例早期OC患者的大样本队列中比较了细胞增殖的两个独立标志物Ki-67和Plk1的mRNA和蛋白质表达,以及它们与临床病理特征和生存的关系。基于标志物表达,我们证明与低表达(Ki-67、Plk1)患者相比,高表达(Ki-67、Plk1)的早期OC患者(I/II期、低级别、浆液性)的无进展生存期(PFS)和总生存期(OS)显著缩短。值得注意的是,基于mRNA表达,这种显著差异在晚期(III/IV期)消失了:至少对于PFS而言,与低表达肿瘤患者相比,高水平的Ki-67和Plk1与适度更好的生存期相关。我们的数据表明,除了Ki-67外,Plk1是早期OC患者分层以最大化治疗效果的新型标志物。与晚期(III/IV期)OC相比,Ki-67和Plk1似乎在早期(I/II期)作为治疗靶点更合适。