Gao Song, Zhao Xiaoyun, Lin Bei, Hu Zhenhua, Yan Limei, Gao Jian
Department of Obstetric and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Tumour Biol. 2012 Oct;33(5):1759-65. doi: 10.1007/s13277-012-0435-y. Epub 2012 Jun 10.
The objective of this study was to examine the expression levels of RE1-silencing transcription factor (REST) and class III β-tubulin (TUBB3) in ovarian cancer and to determine if there is a correlation between their expression and resistance to chemotherapy in ovarian cancer. The protein expression of REST and TUBB3 in ovarian cancer was detected by Western blot analysis. REST expression was inhibited by small interfering ribonucleic acid (siRNA) in human ovarian cancer cell lines. The levels of REST and TUBB3 protein expression were detected by immunohistochemistry. The relationship between REST and TUBB3 expression and chemotherapy resistance, clinicopathological parameters, and prognosis of ovarian cancer was then determined. The present study found that REST was more highly expressed in the ovarian SKOV3 carcinoma cell line compared to the paclitaxel-resistant ovarian cancer cell line, SKOV3/TAX (P = 0.01). In contrast, TUBB3 was more highly expressed in SKOV3/TAX cells compared to SKOV3 cells (P = 0.01). After REST siRNA interference, TUBB3 expression increased in SKOV3 cells. REST expression was significantly higher in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (70.7 % vs. 37.0 %, P < 0.05). However, TUBB3 expression was significantly lower in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (47.6 % vs. 77.8 %, P < 0.05). Notably, REST was more highly expressed in TUBB3-negative cases than TUBB3-positive cases (P < 0.05). Univariate analyses indicated that both REST and TUBB3 expression were unrelated to tumor differentiation, histological type, and clinical stage (all P > 0.05). According to the Cox regression model, negative REST and positive TUBB3 protein expression was detected as independent prognostic factors (P = 0.003 and P = 0.005, respectively). REST and TUBB3 protein may be potential biomarkers for chemoresistance and prognosis in ovarian cancer.
本研究的目的是检测卵巢癌中RE1沉默转录因子（REST）和Ⅲ类β微管蛋白（TUBB3）的表达水平，并确定它们的表达与卵巢癌化疗耐药性之间是否存在相关性。通过蛋白质免疫印迹分析检测卵巢癌中REST和TUBB3的蛋白表达。在人卵巢癌细胞系中，小干扰核糖核酸（siRNA）抑制REST表达。通过免疫组织化学检测REST和TUBB3蛋白表达水平。随后确定REST和TUBB3表达与卵巢癌化疗耐药性、临床病理参数及预后之间的关系。本研究发现，与耐紫杉醇的卵巢癌细胞系SKOV3/TAX相比，REST在卵巢SKOV3癌细胞系中表达更高（P = 0.01）。相反，与SKOV3细胞相比，TUBB3在SKOV3/TAX细胞中表达更高（P = 0.01）。REST siRNA干扰后，SKOV3细胞中TUBB3表达增加。与耐紫杉醇组相比，紫杉醇敏感组中REST表达显著更高（70.7% 对37.0%，P < 0.05）。然而，与耐紫杉醇组相比，紫杉醇敏感组中TUBB3表达显著更低（47.6% 对77.8%，P < 0.05）。值得注意的是，REST在TUBB3阴性病例中比TUBB3阳性病例表达更高（P < 0.05）。单因素分析表明，REST和TUBB3表达均与肿瘤分化、组织学类型及临床分期无关（所有P > 0.05）。根据Cox回归模型，检测到REST阴性和TUBB3蛋白阳性表达为独立预后因素（分别为P = 0.003和P = 0.005）。REST和TUBB3蛋白可能是卵巢癌化疗耐药性和预后的潜在生物标志物。
