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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

Li, Na ; Xu, Hui ; Sun, Xuehua ; Wang, Qiaoli LU orcid ; Qiu, Hui ; Zhou, Yunfeng and Zhou, Fuxiang (2020) In Chinese Journal of Radiological Medicine and Protection 40(9). p.666-673
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... (More)

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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alternative title
Effect of molecular phenotype based on Warburg effect pathway on the prognosis and the efficacy of postoperative radiation in cervical cancer
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cervical cancer, Molecular phenotype, Postoperative radiation, Prognosis, Recurrence
in
Chinese Journal of Radiological Medicine and Protection
volume
40
issue
9
pages
666 - 673
publisher
Chinese Medical Journals Publishing House Co.Ltd
external identifiers
  • scopus:85095702745
ISSN
0254-5098
DOI
10.3760/cma.j.issn.0254-5098.2020.09.003
language
Chinese (Simplified)
LU publication?
no
additional info
Publisher Copyright: Copyright © 2020 by the Chinese Medical Association.
id
b394901f-c1ab-460b-8137-e1871ff69c14
date added to LUP
2025-10-17 12:15:38
date last changed
2025-10-20 08:24:54
@article{b394901f-c1ab-460b-8137-e1871ff69c14,
  abstract     = {{<p>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 (PDK1<sup>high</sup>/p-PDH<sup>high</sup>/PKM2<sup>high</sup>) were positively correlated with pelvic lymphnode metastasis (χ<sup>2</sup>=10.890, 7.407, P&lt;0.05). PDK1<sup>high</sup>/p-PDH<sup>high</sup>/PKM2<sup>high</sup>, 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&lt;0.05). Multivariate analysis showed that PDK1<sup>high</sup> /PDH<sup>high</sup>/PKM2<sup>high</sup>, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS(P&lt;0.05). The verification result of the GEO dataset showed that PDK1<sup>high</sup>/PDH<sup>high</sup>/PKM2<sup>high</sup> was the risk factor for DFS(P&lt;0.05). Pathological type, pelvic lymph node metastasis and PDK1<sup>high</sup>/p-PDH<sup>high</sup>/PKM2<sup>high</sup> could affect the DFS of those patients with postoperative radiation (P&lt;0.05). In addition, the multivariate analysis showed that pathological type and PDK1<sup>high</sup> /p-PDH<sup>high</sup>/PKM2<sup>high</sup> were the independent prognosis factors for DFS(P&lt;0.05). Conclusions: The patients of PDK1<sup>high</sup> /p-PDH<sup>high</sup>/PKM2<sup>high</sup> 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-Ⅱ<sub>B</sub> cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.</p>}},
  author       = {{Li, Na and Xu, Hui and Sun, Xuehua and Wang, Qiaoli and Qiu, Hui and Zhou, Yunfeng and Zhou, Fuxiang}},
  issn         = {{0254-5098}},
  keywords     = {{Cervical cancer; Molecular phenotype; Postoperative radiation; Prognosis; Recurrence}},
  language     = {{chi}},
  month        = {{09}},
  number       = {{9}},
  pages        = {{666--673}},
  publisher    = {{Chinese Medical Journals Publishing House Co.Ltd}},
  series       = {{Chinese Journal of Radiological Medicine and Protection}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.3760/cma.j.issn.0254-5098.2020.09.003}},
  doi          = {{10.3760/cma.j.issn.0254-5098.2020.09.003}},
  volume       = {{40}},
  year         = {{2020}},
}