Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer.
Gynecol Oncol
; 157(2): 437-443, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32107047
ABSTRACT
OBJECTIVE:
Resistance to chemo-radiation therapy is a substantial obstacle that compromises treatment of advanced cervical cancer. The objective of this study was to investigate if a proteomic panel associated with radioresistance could predict survival of patients with locally advanced cervical cancer.METHODS:
A total of 181 frozen tissue samples were prospectively obtained from patients with locally advanced cervical cancer before chemoradiation. Expression levels of 22 total and phosphorylated proteins were evaluated using well-based reverse phase protein arrays. Selected proteins were validated with western blotting analysis and immunohistochemistry. Performances of models were internally and externally validated.RESULTS:
Unsupervised clustering stratified patients into three major groups with different overall survival (OS, P = 0.001) and progression-free survival (PFS, P = 0.003) based on detection of BCL2, HER2, CD133, CAIX, and ERCC1. Reverse-phase protein array results significantly correlated with western blotting results (R2 = 0.856). The C-index of model was higher than clinical model in the prediction of OS (C-index 0.86 and 0.62, respectively) and PFS (C-index 0.82 and 0.64, respectively). The Kaplan-Meier survival curve showed a dose-dependent prognostic significance of risk score for PFS and OS. Multivariable Cox proportional hazard model confirmed that the risk score was an independent predictor of PFS (HR 1.6; 95% CI 1.4-1.9; P < 0.001) and OS (HR 2.1; 95% CI 1.7-2.5; P < 0.001).CONCLUSION:
A proteomic panel of BCL2, HER2, CD133, CAIX, and ERCC1 independently predicted survival in locally advanced cervical cancer patients. This prediction model can help identify chemoradiation responsive tumors and improve prediction for clinical outcome of cervical cancer patients.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Cuello Uterino
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Gynecol Oncol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos