| 厉娜,徐会,孙雪花,王巧丽,邱惠,周云峰,周福祥.基于Warburg效应通路的分子分型对宫颈癌预后和术后放疗疗效的影响[J].中华放射医学与防护杂志,2020,40(9):666-673 |
| 基于Warburg效应通路的分子分型对宫颈癌预后和术后放疗疗效的影响 |
| Effect of molecular phenotype based on Warburg effect pathway on the prognosis and the efficacy of postoperative radiation in cervical cancer |
| 投稿时间：2020-03-15 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.09.003 |
| 中文关键词: 宫颈癌 分子分型 预后 术后放疗 复发 |
| 英文关键词:Cervical cancer Molecular phenotype Prognosis Postoperative radiation Recurrence |
| 基金项目:国家自然科学基金（81773238） |
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| 中文摘要: |
| 目的 研究Warburg效应通路的分子丙酮酸脱氢酶激酶1（pyruvate dehydrogenase kinase 1，PDK1）、磷酸化的丙酮酸脱氢酶（phosphorylated Pyruvate dehydrogenase，p-PDH）和丙酮酸激酶M2型（Pyruvate kinase isozyme type M2，PKM2）在宫颈癌组织中的表达情况，并探讨上述分子对宫颈癌预后和术后放疗疗效的影响。方法 免疫组织化学法检测102例接受根治性手术的宫颈癌患者原发灶组织中PDK1、p-PDH和PKM2的表达水平，其中63例接受术后放疗，分别单独和联合分析三分子的表达对宫颈癌预后和术后放疗疗效的影响。利用GEO数据集300例数据进行mRNA水平验证。生存分析用Kaplan-Meier法，COX回归模型用于单因素和多因素预后分析。结果 PDK1和PDK1high/p-PDHhigh/PKM2high指标同时高表达与盆腔淋巴结转移正相关（χ2=10.890、7.407，P<0.05）。PDK1high/p-PDHhigh/PKM2high、国际妇产科联盟（FIGO）分期、盆腔淋巴结转移和术后放疗是影响总生存（OS）和无病生存（DFS）的因素（P<0.05）；多因素分析显示，PDK1high/PDHhigh/PKM2high、FIGO分期和术后放疗是影响OS和DFS的独立预后因素（P<0.05）。GEO数据集验证结果显示，PDK1high/PDHhigh/PKM2high是DFS的危险因素（P<0.05）。病理分型、盆腔淋巴结转移和PDK1high/p-PDHhigh/PKM2high是术后放疗DFS的影响因素（P<0.05）；多因素分析显示，病理分型和PDK1high/p-PDHhigh/PKM2high（P<0.05）是影响术后放疗DFS的独立预后因素。结论 PDK1high/p-PDHhigh/PKM2high亚型宫颈癌患者预后和术后放疗无复发生存差，此亚型患者可能为Ⅰ~ⅡB期宫颈癌预后不良和术后放疗易复发的高危人群，为宫颈癌的分层治疗提供新思路。 |
| 英文摘要: |
| Objective To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation. Methods The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis. Results High expression of PDK1 and all the three indicators (PDK1high/p-PDHhigh/PKM2high) were positively correlated with pelvic lymphnode metastasis (χ2=10.890, 7.407, P<0.05). PDK1high/p-PDHhigh/PKM2high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) (P<0.05). Multivariate analysis showed that PDK1high/PDHhigh/PKM2high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS(P<0.05). The verification result of the GEO dataset showed that PDK1high/PDHhigh/PKM2high was the risk factor for DFS(P<0.05). Pathological type, pelvic lymph node metastasis and PDK1high/p-PDHhigh/PKM2high could affect the DFS of those patients with postoperative radiation (P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1high/p-PDHhigh/PKM2high were the independent prognosis factors for DFS(P<0.05). Conclusions The patients of PDK1high/p-PDHhigh/PKM2high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-ⅡB cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer. |
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