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DEK与卵巢癌中凋亡调节因子相关的临床病理见解及预后意义

Clinicopathological insights and prognostic implications of DEK in association with apoptosis-regulating factors in ovarian cancer.

作者信息

Choudhury Trisha, Pal Ranita, Ghosh Madhurima, Chatterjee Sriparna, Sarkar Sinjini, Vernekar Manisha, Nath Partha, Nasare Vilas D

机构信息

Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India.

Department of Life Science & Biotechnology, Jadavpur University, Kolkata, 700032, India.

出版信息

Clin Transl Oncol. 2025 May 20. doi: 10.1007/s12094-025-03944-8.

Abstract

PURPOSE

Ovarian cancer is one of the most common gynecologic malignancies of the present era. Dysregulation of apoptosis is considered as one of the most important factors for malignant transformation. DEK is a ubiquitous protein, and its downregulation induces apoptosis by altering BCL-2, BAX, and CASPASE-3 expressions. This study illuminates the cumulative clinical usefulness of DEK and related apoptotic proteins.

METHODS

A total of 119 patients were enrolled during 2021-2023. Demographic and clinicopathological data were recorded at presentation, and the follow-up was done till August 2024. Tissue samples were analyzed using immunohistochemistry and real-time PCR. A paired t test assessed gene expression between normal and malignant tissues of different treatment strategies. The crosstab was performed to find the association of DEK, BCL-2, BAX, and CASPASE-3 with clinicopathological features. Pearson's correlation was used to predict the association of DEK with other apoptotic factors. Survival and hazard risk were evaluated using log-rank and Cox regression.

RESULTS

The mean age of OC patients was 47.61 ± 12.5 years, presented with advanced stage (90.7%) and grade (85.3%). Most of them were post-menopausal (68.08%) and had unhygienic (76.5%) regular menstrual cycles (89.1%), and also experienced early pregnancy (61.8%). Some of these factors are related to a hazard risk (HR > 1). DEK and apoptotic proteins were upregulated in OC than in normal (p ≤ 0.01). DEK was positively correlated with BCL-2, BAX, and CASPASE-3, at both mRNA and protein levels, and only BAX showed significance in both (p ≤ 0.05). All the selected genes are independent risk factors for survival of OC (HR > 1), but only DEK and CASPASE-3 were significantly associated with poor survival (p ≤ 0.05).

CONCLUSIONS

Dysregulation of DEK, CASPASE-3, and BAX/BCL-2 is associated with poor overall survival. Further, this study highlights the correlation between DEK and key apoptotic regulators, emphasizing the critical role of DEK in OC prognosis.

摘要

目的

卵巢癌是当代最常见的妇科恶性肿瘤之一。细胞凋亡失调被认为是恶性转化的最重要因素之一。DEK是一种普遍存在的蛋白质,其下调通过改变BCL-2、BAX和CASPASE-3的表达诱导细胞凋亡。本研究阐明了DEK和相关凋亡蛋白的累积临床应用价值。

方法

2021年至2023年共纳入119例患者。记录患者就诊时的人口统计学和临床病理数据,并随访至2024年8月。使用免疫组织化学和实时PCR分析组织样本。配对t检验评估不同治疗策略的正常组织和恶性组织之间的基因表达。进行交叉表分析以发现DEK、BCL-2、BAX和CASPASE-3与临床病理特征的关联。采用Pearson相关性分析预测DEK与其他凋亡因子的关联。使用对数秩检验和Cox回归评估生存率和风险。

结果

卵巢癌患者的平均年龄为47.61±12.5岁,多为晚期(90.7%)和高分级(85.3%)。大多数患者为绝经后(68.08%),月经周期不规律(76.5%),月经周期正常者占89.1%,且有早孕史(61.8%)。其中一些因素与风险(HR>1)相关。与正常组织相比,卵巢癌组织中DEK和凋亡蛋白表达上调(p≤0.01)。在mRNA和蛋白水平上,DEK均与BCL-2、BAX和CASPASE-3呈正相关,但仅BAX在两者中均具有显著性(p≤0.05)。所有选定基因均为卵巢癌生存的独立危险因素(HR>1),但只有DEK和CASPASE-3与不良生存显著相关(p≤0.05)。

结论

DEK、CASPASE-3和BAX/BCL-2的失调与总体生存率低有关。此外,本研究强调了DEK与关键凋亡调节因子之间的相关性,突出了DEK在卵巢癌预后中的关键作用。

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