Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.
Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5021, Bergen, Norway.
BMC Cancer. 2018 Jun 25;18(1):684. doi: 10.1186/s12885-018-4591-3.
Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here we attempt to further portray the p53 pathway in USC by assessing p53 isoform expression.
We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses of total p53 mRNA as well as quantitative distinction of p53β, p53γ, and the total mRNA of amino-terminal truncated Δ40p53 and Δ133p53 in a retrospective cohort of 37 patients with USC. TP53 mutation status was assessed by targeted massive parallel sequencing. Findings were correlated with clinical data.
The p53 isoform expression landscape in USCs was heterogeneous and dominated by total Δ133p53, while the distinct p53β and p53γ variants were found at much lower levels. The isoform expression profiles varied between samples, while their expression was independent of TP53 mutation status. We found high relative p53γ expression to be associated with reduced progression-free survival (PFS).
This is the first indication that elevated p53γ expression is associated with reduced PFS in USC. This single-center study may offer some insight in the landscape of p53 isoform expression in USC, but further validation studies are crucial to understand the context-dependent and tissue-specific role of the p53 isoform network in gynecological cancer.
子宫浆液性癌（USC）是一种罕见但侵袭性较强的子宫内膜癌亚型。大规模的综合努力使人们对其发病机制的分子理解得到了改善，p53 途径被认为是一个关键因素，并且具有潜在的靶向性。在这里，我们试图通过评估 p53 异构体的表达来进一步描绘 USC 中的 p53 途径。
我们应用定量实时 PCR（RT-qPCR）分析了 37 例 USC 患者的总 p53 mRNA 表达以及 p53β、p53γ 和氨基末端截断的 Δ40p53 和 Δ133p53 的总 mRNA 的定量区分。通过靶向大规模平行测序评估 TP53 突变状态。并将结果与临床数据相关联。
USC 中的 p53 异构体表达谱呈异质性，主要由总 Δ133p53 主导，而明显的 p53β 和 p53γ 变体的水平则较低。样品之间的异构体表达谱不同，而它们的表达与 TP53 突变状态无关。我们发现相对较高的 p53γ 表达与无进展生存期（PFS）降低有关。
这是第一个表明在 USC 中 p53γ 表达升高与 PFS 降低相关的迹象。这项单中心研究可能为 USC 中 p53 异构体表达的全貌提供了一些见解，但进一步的验证研究对于理解 p53 异构体网络在妇科癌症中的组织特异性和上下文依赖性作用至关重要。
