Wip1-p38-p53 DNA 损伤反应通路在卵巢透明细胞癌早期/晚期中的差异作用。

Differential roles of the Wip1-p38-p53 DNA damage response pathway in early/advanced-stage ovarian clear cell carcinomas.

机构信息

Doctoral Program in Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tsukuba, Ibaraki, 305-8577, Japan.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tsukuba, Ibaraki, 305-8575, Japan.

出版信息

World J Surg Oncol. 2022 Apr 30;20(1):139. doi: 10.1186/s12957-022-02600-7.

DOI:10.1186/s12957-022-02600-7

PMID:35490254

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9055709/

Abstract

BACKGROUND

Ovarian clear cell carcinoma (OCCC) is one of the most lethal types of ovarian cancer. Early-stage OCCC can be cured by surgery; however, advanced-stage disease shows poor prognosis due to chemoresistance unlike the more common high-grade serous carcinoma.

METHODS

We explored the differential roles of the Wip1-p38-p53 DNA damage response pathway in respective early- or advanced-stage OCCC by immunohistochemistry of Wip1, phospho-p38, p53, and phospho-p53 from consecutive 143 patients.

RESULTS

High Wip1 expression correlated with positive p53 (p=0.011), which in turn correlated with low nuclear phospho-p38 expression (p=0.0094). In the early stages, positive p53 showed trends toward worse overall survival (OS) (p=0.062), whereas in the advanced stages, high Wip1 correlated with worse OS (p=0.0012). The univariate and multivariate analyses of prognostic factors indicated that high Wip1 was significant and independent for worse OS (p=0.011) in the advanced stages, but not in the early stages. Additionally, high Wip1 showed trends toward shorter treatment-free interval (TFI) in the advanced stages, but not in the early stages (p=0.083 vs. 0.93). Furthermore, high Wip1 was significantly associated with positive p53 only in the patients with shorter TFI (<6 months), but not in those with longer TFI (≥6 months) (p=0.036 vs. 0.34).

CONCLUSIONS

Wip1 appears to play a crucial role for the prognosis of OCCC through chemoresistance specifically in the advanced stages, implicating that Wip1 possibly serves as a reasonable therapeutic target for improving chemoresistance and poor prognosis of advanced-stage OCCC.

摘要

背景

卵巢透明细胞癌（OCCC）是卵巢癌中最致命的类型之一。早期 OCCC 可以通过手术治愈；然而，与更常见的高级别浆液性癌不同，晚期疾病表现出化疗耐药，预后较差。

方法

我们通过对连续 143 例患者的 Wip1、磷酸化 p38、p53 和磷酸化 p53 的免疫组织化学研究，探讨了 Wip1-p38-p53 DNA 损伤反应通路在早期或晚期 OCCC 中的差异作用。

结果

高 Wip1 表达与阳性 p53 相关（p=0.011），而 p53 又与核磷酸化 p38 表达降低相关（p=0.0094）。在早期阶段，阳性 p53 与总生存期（OS）较差呈趋势相关（p=0.062），而在晚期阶段，高 Wip1 与 OS 较差相关（p=0.0012）。预后因素的单因素和多因素分析表明，在晚期阶段，高 Wip1 是 OS 较差的显著和独立因素（p=0.011），但在早期阶段则不是。此外，高 Wip1 与晚期患者的无治疗间隔（TFI）较短呈趋势相关，但在早期阶段则不是（p=0.083 与 0.93）。此外，高 Wip1 仅与 TFI 较短（<6 个月）的患者的阳性 p53显著相关，而与 TFI 较长（≥6 个月）的患者则不相关（p=0.036 与 0.34）。