Wang Yi-Qin, Xu Mi-Die, Weng Wei-Wei, Wei Ping, Yang Yu-Si, Du Xiang
Department of Pathology, Fudan University Shanghai Cancer Center Shanghai, 200032, China ; Department of Oncology, Fudan University Shanghai Cancer Center Shanghai, 200032, China ; Institute of Pathology, Fudan University Shanghai 200032, China ; Institute of Biomedical Sciences, Fudan University Shanghai, 200032, China ; Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University Shanghai, 200032, China ; Department of Pathology, Shanghai Medical College, Fudan University Shanghai, 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center Shanghai, 200032, China ; Department of Oncology, Fudan University Shanghai Cancer Center Shanghai, 200032, China ; Institute of Pathology, Fudan University Shanghai 200032, China ; Institute of Biomedical Sciences, Fudan University Shanghai, 200032, China.
Am J Cancer Res. 2014 Dec 15;5(1):255-66. eCollection 2015.
Dysregulation of BCL6 plays critical oncogenic roles and facilitates tumorigenesis in various malignancies. However, whether the aberrant expression of BCL6 in ovarian carcinoma is associated with malignancy, metastasis or prognosis remains unknown. Our study aimed to investigate the expression of BCL6 in ovarian carcinoma and its possible correlation with clinicopathological features as well as patient survival to reveal its biological effects in ovarian tumor progression.
Immunochemistry analysis was performed in 105 cases of ovarian carcinoma covering the histological types of serous, endometrioid and clear cell. Spearman analysis was used to calculate the correlation between pathological parameters and the expression of BCL6. Kaplan-Meier method and Cox proportional hazards analysis were used to analyze the disease-specific survival (DSS) and disease-free survival (DFS). We also assessed whether overexpression and knockdown of BCL6 influence in vitro cell proliferation, cell cycle progression, as well as tumor cell invasion and migration.
The expression of BCL6 was higher in all three major kinds of ovarian cancer in comparison with paratumorous epithelium. BCL6 expression was tightly correlated with FIGO staging, lymph node metastasis and recurrence. Higher expression of BCL6 led to a significantly poorer DSS and DFS and multivariate analysis revealed that BCL6 was an independent risk factor of DSS and DFS. Enforced overexpression of BCL6 in ovarian tumor cells stimulated proliferation by inducing G1-S transition, and promoted tumor cell invasion and migration. Conversely, RNA interference-mediated silencing BCL6 expression inhibited proliferation by altered cell cycle progression and reduced the ability of the cells to migrate, and invade the extracellular matrix in culture.
Our study suggests that the inappropriate activation of BCL6 predicts poor prognosis and promotes tumor progression in ovarian carcinoma. Targeting BCL6 could be a novel therapeutic choice for treating ovarian carcinoma patients.
BCL6的失调在多种恶性肿瘤中发挥关键的致癌作用并促进肿瘤发生。然而，BCL6在卵巢癌中的异常表达是否与恶性程度、转移或预后相关仍不清楚。我们的研究旨在调查BCL6在卵巢癌中的表达及其与临床病理特征以及患者生存的可能相关性，以揭示其在卵巢肿瘤进展中的生物学作用。
对105例涵盖浆液性、子宫内膜样和透明细胞组织学类型的卵巢癌进行免疫化学分析。采用Spearman分析计算病理参数与BCL6表达之间的相关性。采用Kaplan-Meier法和Cox比例风险分析评估疾病特异性生存（DSS）和无病生存（DFS）。我们还评估了BCL6的过表达和敲低是否影响体外细胞增殖、细胞周期进程以及肿瘤细胞的侵袭和迁移。
与癌旁上皮相比，BCL6在所有三种主要类型的卵巢癌中的表达均较高。BCL6表达与国际妇产科联盟（FIGO）分期、淋巴结转移和复发密切相关。BCL6的高表达导致DSS和DFS显著较差，多变量分析显示BCL6是DSS和DFS的独立危险因素。在卵巢肿瘤细胞中强制过表达BCL6通过诱导G1-S期转变刺激增殖，并促进肿瘤细胞的侵袭和迁移。相反，RNA干扰介导的BCL6表达沉默通过改变细胞周期进程抑制增殖，并降低细胞在培养中迁移和侵袭细胞外基质的能力。
我们的研究表明，BCL6的不适当激活预示着卵巢癌预后不良并促进肿瘤进展。靶向BCL6可能是治疗卵巢癌患者的一种新的治疗选择。
