Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma.

Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma.
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DOI:
10.1371/journal.pone.0060516
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Xie D
Xie D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lin HX;Qiu HJ;Zeng F;Rao HL;Yang GF;Kung HF;Zhu XF;Zeng YX;Cai MY;Xie D

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已有研究表明,自噬相关的Beclin 1在肿瘤发生和/或进展的调控中起着关键作用,但其在卵巢癌中的预后意义及其与Bcl-xL表达的关系尚不清楚。本研究采用Western blotting和免疫组化(IHC)方法研究Beclin 1和Bcl-xL在新鲜卵巢组织和石蜡包埋卵巢上皮肿瘤组织中的表达情况。在8.3%的正常卵巢、15.4%的囊腺瘤、20.0%的交界性肿瘤和55.6%的卵巢癌中,IHC检测到Beclin 1表达降低。在卵巢癌中,Beclin 1表达降低与组织学分级升高、pT/pN/pM水平升高和/或临床分期晚期密切相关(P<0.05)。在单因素生存分析中,卵巢癌患者Beclin 1低表达与患者生存期缩短极显著相关(P<0.01),多因素分析表明Beclin 1表达是独立的预后因素(P = 0.013)。此外,在卵巢癌队列中Beclin 1表达降低与Bcl-xL表达改变呈负相关,联合分析进一步表明Beclin 1低/ Bcl-xL高组生存率最低。我们的研究结果表明,IHC检测的Beclin 1表达可以作为鉴定卵巢癌患者肿瘤进展风险的额外工具,并预测Bcl-xL表达增加的卵巢癌患者的生存。
It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear. In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate. Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.
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