Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma
Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma
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Beclin 1的异常表达与卵巢上皮癌的发生、分化、进展和预后密切相关
DOI：
10.1007/s13277-013-1261-6
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发表时间：
2014-03-01
期刊：
影响因子：
--
通讯作者：
Zheng, Hua-chuan
中科院分区：
文献类型：
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作者：
Zhao, Yang;Chen, Shuo;Zheng, Hua-chuan
Beclin 1是人类细胞中重要的自噬相关蛋白，参与自噬、分化、抗凋亡、抑癌等过程，在细胞应激期间增加，在细胞周期中消失。人卵巢肿瘤Beclin 1等位基因丢失频率高。为了阐明beclin 1在卵巢癌发生和随后的进展中的作用，我们在包含卵巢正常组织、良性和交界性肿瘤以及癌的组织微阵列上通过免疫染色检测了beclin 1的表达。采用逆转录聚合酶链反应和Western blot检测Beclin 1mRNA和蛋白在卵巢正常组织、良性和交界性肿瘤组织、癌组织和细胞系中的表达。结果显示，卵巢良性肿瘤beclin 1mRNA表达水平高于正常卵巢和卵巢癌（P< 0.05），且与卵巢癌的分化呈负相关（P< 0.05）。Beclin 1蛋白在卵巢癌组织中的表达强于正常卵巢组织，且与卵巢癌的分化呈负相关（P< 0.05）。免疫组化结果显示，Beclin 1在卵巢交界性肿瘤和恶性肿瘤中的表达高于正常卵巢和良性肿瘤（P< 0.05），且与分化呈负相关，ki-67表达较低，卵巢癌的累积生存率或无复发生存率较高（P< 0.05）。Cox比例风险模型显示，年龄和国际妇产联合会分期（P< 0.05）是影响整体卵巢癌和无复发卵巢癌预后的独立因素，而非病理分型、分化程度和Beclin 1表达（P< 0.05）。提示Beclin 1的异常表达与卵巢癌的发生、分化密切相关。Beclin 1的表达可能预示卵巢癌预后较差，但不是一个独立的因素。
Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer suppression, which is increased during periods of cell stress and extinguished during cell cycle. Human ovarian tumors display allelic loss of Beclin 1 with high frequency. To clarifyBeclin 1's role in ovarian carcinogenesis and subsequent progression, its expression was examined by immunostaining on tissue microarrays containing ovarian normal tissue, benign and borderline tumors, and carcinomas.Beclin 1mRNA and protein expression was examined in ovarian normal tissue, benign and borderline tumors, carcinoma tissue, and cell lines by reverse transcription polymerase chain reaction or Western blot, respectively. The results demonstrated that the higherBeclin 1mRNA was observed in ovarian benign tumor than normal ovary and ovarian carcinoma (P< 0.05) and negatively correlated with the differentiation of ovarian carcinoma (P< 0.05). Beclin 1 protein expression was stronger in ovarian carcinoma than that in normal ovary and inversely related to the differentiation of ovarian carcinoma (P< 0.05) by Western blot. Immunohistochemically, Beclin 1 expression was statistically higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumor (P< 0.05) and inversely linked to differentiation, lower ki-67 expression, and higher cumulative or relapse-free survival rate of ovarian carcinoma (P< 0.05). Cox proportional hazard model indicated that age and International Federation of Gynecology and Obstetrics staging (P< 0.05), but not pathological classification differentiation degree or Beclin 1 expression, were independent prognostic factors for overall and relapse-free ovarian carcinomas (P> 0.05). It was suggested that the aberrant Beclin 1 expression is closely linked to tumorigenesis and differentiation of ovarian carcinoma. Beclin 1 expression might be employed to indicate the worse prognosis of ovarian carcinomas, albeit not an independent factor.