| Li Na,Xu Hui,Sun Xuehua,Wang Qiaoli,Qiu Hui,Zhou Yunfeng,Zhou Fuxiang.Effect of molecular phenotype based on Warburg effect pathway on the prognosis and the efficacy of postoperative radiation in cervical cancer[J].Chinese Journal of Radiological Medicine and Protection,2020,40(9):666-673 |
| Effect of molecular phenotype based on Warburg effect pathway on the prognosis and the efficacy of postoperative radiation in cervical cancer |
| Received:March 15, 2020 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.09.003 |
| KeyWords:Cervical cancer Molecular phenotype Prognosis Postoperative radiation Recurrence |
| FundProject:国家自然科学基金（81773238） |
| Author Name | Affiliation | E-mail | | Li Na | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | | | Xu Hui | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | | | Sun Xuehua | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | | | Wang Qiaoli | Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm 17177, Sweden | | | Qiu Hui | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | | | Zhou Yunfeng | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | | | Zhou Fuxiang | Department of Radiation&Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China | happyzhoufx@sina.com |
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| Abstract:: |
| 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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