The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
PLoS One. 2013;8(4):e60516. doi: 10.1371/journal.pone.0060516. Epub 2013 Apr 3.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
自噬相关蛋白 Beclin 1 被认为在肿瘤发生和/或进展的调控中发挥着关键作用，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。
方法/主要发现：本研究采用 Western blot 和免疫组化（IHC）方法检测新鲜卵巢组织和石蜡包埋上皮性卵巢肿瘤组织中 Beclin 1 和 Bcl-xL 的表达状态。通过 IHC 检测，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%的卵巢癌中观察到 Beclin 1 的表达下调。在卵巢癌中，Beclin 1 的表达下调与组织学分级升高、晚期 pT/pN/pM 分期和/或临床晚期密切相关（P<0.05）。单因素生存分析显示，Beclin 1 低表达与卵巢癌患者生存期缩短显著相关（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，Beclin 1 的表达下调与卵巢癌患者中 Bcl-xL 表达的改变呈负相关，联合分析进一步表明，Beclin 1 低表达/ Bcl-xL 高表达组的生存率最低。
结论/意义：本研究提示，通过 IHC 检测 Beclin 1 表达可以作为一种额外的工具，用于识别有肿瘤进展风险的卵巢癌患者，并预测 Bcl-xL 高表达的卵巢癌患者的生存情况。
