Zhao Yang, Chen Shuo, Gou Wen-feng, Xiao Li-jun, Takano Yasuo, Zheng Hua-chuan
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Tumour Biol. 2014 Mar;35(3):1955-64. doi: 10.1007/s13277-013-1261-6. Epub 2013 Oct 17.
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 clarify Beclin 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 1 mRNA 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 higher Beclin 1 mRNA 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.
Beclin 1是人类细胞中一种重要的自噬相关蛋白,参与自噬、分化、抗凋亡及癌症抑制过程,在细胞应激期间表达增加,在细胞周期中消失。人类卵巢肿瘤中Beclin 1基因高频等位基因缺失。为阐明Beclin 1在卵巢癌发生及后续进展中的作用,通过免疫染色检测了其在包含卵巢正常组织、良性和交界性肿瘤以及癌组织的组织芯片上的表达。分别通过逆转录聚合酶链反应或蛋白质免疫印迹法检测了卵巢正常组织、良性和交界性肿瘤、癌组织及细胞系中Beclin 1的mRNA和蛋白表达。结果显示,卵巢良性肿瘤中Beclin 1的mRNA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)。蛋白质免疫印迹法显示,卵巢癌中Beclin 1蛋白表达强于正常卵巢,且与卵巢癌的分化呈负相关(P < 0.05)。免疫组化结果表明,卵巢交界性肿瘤和癌组织中Beclin 1的表达在统计学上高于正常卵巢和良性肿瘤(P < 0.05),且与分化、较低的Ki-67表达以及较高的卵巢癌累积生存率或无复发生存率呈负相关(P < 0.05)。Cox比例风险模型表明,年龄和国际妇产科联盟分期(P < 0.05)是卵巢癌总体生存率和无复发生存率的独立预后因素,而病理分类分化程度或Beclin 1表达不是(P > 0.05)。提示Beclin 1表达异常与卵巢癌的发生和分化密切相关。Beclin 1表达可能用于提示卵巢癌预后较差,尽管不是独立因素。