载脂蛋白B mRNA编辑酶催化多肽样3B上调独立预测卵巢癌预后：一项队列研究
APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study.
作者信息
Du Yan, Tao Xiang, Wu Jing, Yu Huandi, Yu Yinhua, Zhao Hongbo
机构信息
1Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Rd, 200011 Shanghai, People's Republic of China.
2The Academy of Integrative Medicine of Fudan University, 200011 Shanghai, People's Republic of China.
出版信息
Cancer Cell Int. 2018 May 29;18:78. doi: 10.1186/s12935-018-0572-5. eCollection 2018.
BACKGROUND
Ovarian cancer is a heterogeneous disease with a high degree of genomic instability, pro-/antitumor immunity and inflammation, and remains the most lethal gynecologic cancer worldwide. APOBEC3B, a member of the AID/APOBEC family, is part of the innate immune system which plays a key role in combating exogenous infection especially viral infection. Studies have shown that APOBEC3B expression is elevated in a variety of cancer tissues and cell lines, and plays a prominent role in the genesis and evolution of various cancers. However, the clinical relevance of APOBEC3B in ovarian cancer needs to be further investigated. The current study aimed to evaluate the predictive value of APOBEC3B in ovarian cancer clinical outcome, and to explore possible molecular mechanisms contributing to ovarian cancer progression.
METHODS
The expression of APOBEC3B in biopsy tissue specimens from 88 ovarian cancer patients was examined using immunohistochemistry. In addition, ovarian cancer cell lines were transfected with APOBEC3B siRNA or pLenti-APOBEC3B construct. Western blotting and SRB assay were performed to explore the role of APOBEC3B in ovarian cancer.
RESULTS
Patients were followed for a median of 74.77 months following the time of surgery. Forty-two patients had died, 5 had relapsed but were still alive at the end of study, and 41 patients remained alive and had no recurrence. Over-expression of APOBEC3B was associated with advanced FIGO stage and elevated CA125 (both p< 0.05). Univariate analysis result showed that histological subtype, FIGO stage, intravascular tumor thrombus, CA125 and expression were associated with overall survival and disease-free survival of ovarian cancer patients. Multivariate analysis result showed that higher expression were an independent prognostic factor to predict both worse overall survival (hazard ratio: 5.18, 95% confidence interval: 1.40-11.95, p= 0.003) and disease-free survival (hazard ratio: 4.23, 95% confidence interval: 1.60-11.17, p= 0.004) of ovarian cancer patients. Furthermore, knockdown of expression in ovarian cancer cells caused an decrease in cell line viability.
CONCLUSIONS
expression is an independent prognostic factor in ovarian cancer patients. Knockdown of expression affects ovarian cancer viability.
背景
卵巢癌是一种异质性疾病，具有高度的基因组不稳定性、促/抗肿瘤免疫和炎症，仍然是全球最致命的妇科癌症。载脂蛋白B mRNA编辑酶催化多肽样3B（APOBEC3B）是AID/APOBEC家族的成员，是先天免疫系统的一部分，在抵抗外源感染尤其是病毒感染中起关键作用。研究表明，APOBEC3B在多种癌组织和细胞系中表达升高，在各种癌症的发生和发展中起重要作用。然而，APOBEC3B在卵巢癌中的临床相关性有待进一步研究。本研究旨在评估APOBEC3B对卵巢癌临床结局的预测价值，并探讨其促进卵巢癌进展的可能分子机制。
方法
采用免疫组织化学法检测88例卵巢癌患者活检组织标本中APOBEC3B的表达。此外，用APOBEC3B小干扰RNA（siRNA）或慢病毒载体介导的APOBEC3B表达载体转染卵巢癌细胞系。采用蛋白质免疫印迹法和磺酰罗丹明B（SRB）法探讨APOBEC3B在卵巢癌中的作用。
结果
患者术后中位随访74.77个月。42例患者死亡，5例复发但在研究结束时仍存活，41例患者存活且无复发。APOBEC3B高表达与国际妇产科联盟（FIGO）晚期和糖类抗原125（CA125）升高相关（均P<0.05）。单因素分析结果显示，组织学亚型、FIGO分期、血管内肿瘤血栓、CA125和APOBEC3B表达与卵巢癌患者的总生存期和无病生存期相关。多因素分析结果显示，APOBEC3B高表达是预测卵巢癌患者总生存期较差（风险比：5.18，95%置信区间：1.4011.95，P=0.003）和无病生存期较差（风险比：4.23，95%置信区间：1.6011.17，P=0.004）的独立预后因素。此外，敲低卵巢癌细胞中APOBEC3B的表达导致细胞系活力下降。
结论
APOBEC3B表达是卵巢癌患者的独立预后因素。敲低APOBEC3B表达影响卵巢癌活力。
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