丙酮酸脱氢酶激酶1在卵巢癌中的表达及临床意义
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国家自然科学基金(81772779);江苏省六大高峰人才项目(2015?WSN?034);江苏省重点人才基金(ZDRCA2016003);江苏省“科教强卫工程”实验诊断学重点实验室(ZDXKB2016005)


Expression and roles of pyruvate dehydrogenase kinase 1 in ovarian cancer
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    摘要:

    目的:研究肿瘤代谢重组中糖代谢基因丙酮酸脱氢酶激酶1(pyruvate dehydrogenase kinase 1,PDK1)在卵巢癌(ovarian cancer,OC)组织中的表达水平及其与临床病理特征和患者预后的关系。方法:实时荧光定量PCR法分别检测PDK1在卵巢癌细胞系SKOV3、人卵巢上皮细胞系HOSEpiC、卵巢良性肿瘤(benign ovarian tumor,BOT)和OC组织中mRNA表达水平;免疫组织化学染色法检测PDK1在BOT及OC组织中蛋白表达水平,并采用单因素和多因素Logistics回归分析PDK1表达与OC患者临床病理特征的关系;采用Kaplan-Meier法进行生存分析。结果:PDK1 mRNA在SKOV3细胞中平均表达水平较人HOSEpiC显著升高(t=38.60,P<0.001);OC组织中PDK1 mRNA平均表达水平显著高于BOT组织(t=2.411,P=0.022);免疫组织化学染色法示OC组织切片中PDK1平均表达水平显著高于BOT组织(χ2=33.874,P<0.001);PDK1高表达与淋巴结转移明显相关,与患者年龄、肿瘤大小、肿瘤分化程度、单双侧发病、包膜是否完整无明显相关,且淋巴结转移是影响PDK1在卵巢癌组织中表达的独立危险因素。进一步生存分析示高表达PDK1的患者具有较差的预后(χ2=4.455,P=0.035)。结论:PDK1在卵巢癌组织中高表达,其作为糖代谢关键酶丙酮酸脱氢酶(pyruvate dehydrogenase,PDH)抑制酶,参与肿瘤细胞代谢重组的过程,在卵巢癌进展中可能发挥促进作用,可作为判断OC不良预后的参考指标。

    Abstract:

    Objective:To study the expression level of pyruvate dehydrogenase kinase 1(PDK1)in ovarian cancer(OC)tissues and its correlation with clinicopathological characteristics and prognostic factors. Methods:Real time PCR was used to detect the mRNA expression of PDK1 in ovarian cancer cell line SKOV3 and human ovarian epithelial cell line HOSEpiC. Real time PCR was used to detect the mRNA expression levels of PDK1 in patients with benign ovarian tumor(BOT)and ovarian cancer. Immunohistochemistry was used to detect the expression of PDK1 in ovarian benign tumors and ovarian cancer tissues. Univariate and multivariate logistics regression analysis was used to analyze the relationship between PDK1 expression and OC clinicopathological characteristics,and survival analysis was performed by Kaplan-Meier. Results:The average expression level of PDK1 mRNA in the ovarian cancer cell line SKOV3was significantly higher than that of human ovarian epithelial cell line HOSEpiC(t=38.60,P<0.001). The average expression level of PDK1 mRNA in ovarian cancer tissues was significantly higher than that in ovarian benign tumor tissues(t=2.411,P=0.022). The immunohistochemical staining showed that the average expression level of PDK1 protein in the ovarian cancer tissue was significantly higher than that of the benign ovarian tumor tissue(χ2=33.874,P<0.001). The high expression of PDK1 was obviously associated with lymph node metastasis by univariate and multivariate logistics regression analysis,and had no significant correlation with age,tumor size,tumor differentiation,unilateral bilateral onset,and the completeness of the envelope. Furthermore,lymph node metastasis is an independent risk factor affecting PDK1 expression in ovarian cancer tissues. Patients with high expression of PDK1 had poor prognosis(χ2=4.455,P=0.035). Conclusion:PDK1 is highly expressed in ovarian cancer tissue,as an inhibitory enzyme of pyruvate dehydrogenase(PDH),PDK1 is involved in the process of tumor cell metabolism and recombination,and may play a pivotal role in the progress of ovarian cancer. It also can be used as a reference index to judge the poor prognosis of ovarian carcinoma.

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姚莎莎,王 进,尚文雯,徐 睿,陈 献,王 芳.丙酮酸脱氢酶激酶1在卵巢癌中的表达及临床意义[J].南京医科大学学报(自然科学版),2019,(1):67-71

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  • 收稿日期:2018-03-17
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  • 在线发布日期: 2019-02-21
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