DDB1 的表达与上皮性卵巢癌的亚型相关，并预测临床结局。

Expression of DDB1 is associated with subtypes of epithelial ovarian cancer and predicts clinical outcomes.

机构信息

National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Eastern District, Beijing 100730, China; Department of Gynecology and Obstetrics, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, No. 32, West Second Section, First Ring Road, Chengdu, Sichuan Province 610072, China.

出版信息

Tissue Cell. 2023 Jun;82:102072. doi: 10.1016/j.tice.2023.102072. Epub 2023 Mar 15.

DOI:10.1016/j.tice.2023.102072

PMID:36934683

Abstract

BACKGROUND

Ovarian cancer is the most lethal gynaecological malignancy. Damage specific DNA-binding protein 1 (DDB1) functions in nucleotide-excision repair and has been reported to be involved in cancer development. In this study, we aimed to determine the expression levels of DDB1 and their association with the clinical outcomes of patients with ovarian cancer.

METHODS

Tissue arrays were performed on 54 epithelial ovarian cancer (EOC) samples. Immunohistochemistry was performed to determine DDB1 expression. DDB1 expression levels among different EOC subtypes were analysed via one-way analysis of variance using SPSS Statistics 19.0. Correlation between DDB1 expression and chemotherapy course/progression-free survival (PFS) of patients was determined via Kaplan-Meier survival analysis using GraphPad Prism 5. Moreover, knockdown of DDB1 in ovarian cancer cells ES2 and OVCAR3 was used to preliminarily validate the role of DDB1.

RESULTS

DDB1 was detected in the cytoplasm, especially in the nucleus, of all subtypes of EOC. However, DDB1 expression levels were significantly different between clear cell carcinoma and low-grade serous carcinoma (P = 0.022) and clear cell carcinoma and endometrioid cancer (P = 0.016). In addition, DDB1 expression was not significantly correlated with chemotherapy course (P = 0.433) or PFS (P = 0.566). High expression levels of DDB1 were correlated with significantly worse overall survival (P = 0.017) in patients with EOC. In addition, DDB1 knockdown in ovarian cancer cells decreased their proliferation in vitro.

CONCLUSION

Our results revealed that DDB1 expression is heterogeneous in ovarian cancer, suggesting its use as a potential biomarker for poor survival in ovarian cancer.

摘要

背景

卵巢癌是最致命的妇科恶性肿瘤。损伤特异性 DNA 结合蛋白 1（DDB1）在核苷酸切除修复中发挥作用，据报道其与癌症的发展有关。在本研究中，我们旨在确定 DDB1 的表达水平及其与卵巢癌患者临床结局的关系。

方法

对 54 例上皮性卵巢癌（EOC）样本进行组织微阵列分析。采用免疫组织化学法检测 DDB1 的表达。采用 SPSS Statistics 19.0 软件进行单因素方差分析，分析不同 EOC 亚型之间 DDB1 表达水平的差异。采用 GraphPad Prism 5 软件的 Kaplan-Meier 生存分析确定 DDB1 表达与患者化疗疗程/无进展生存期（PFS）的相关性。此外，在卵巢癌细胞 ES2 和 OVCAR3 中敲低 DDB1，初步验证 DDB1 的作用。

结果

DDB1 被检测到在所有 EOC 亚型的细胞质中，特别是在细胞核中。然而，DDB1 的表达水平在透明细胞癌和低级别浆液性癌（P=0.022）以及透明细胞癌和子宫内膜样癌（P=0.016）之间有显著差异。此外，DDB1 表达与化疗疗程（P=0.433）或 PFS（P=0.566）无显著相关性。DDB1 高表达与 EOC 患者总生存期明显更差相关（P=0.017）。此外，在卵巢癌细胞中敲低 DDB1 可降低其体外增殖能力。