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DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis
Cervical cancer cells commonly harbour a defective G(1)/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G(2)/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 c...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773222/ https://www.ncbi.nlm.nih.gov/pubmed/26930412 http://dx.doi.org/10.1371/journal.pone.0149872 |
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author | Vici, Patrizia Buglioni, Simonetta Sergi, Domenico Pizzuti, Laura Di Lauro, Luigi Antoniani, Barbara Sperati, Francesca Terrenato, Irene Carosi, Mariantonia Gamucci, Teresa Dattilo, Rosanna Bartucci, Monica Vincenzoni, Cristina Mariani, Luciano Vizza, Enrico Sanguineti, Giuseppe Gadducci, Angiolo Vitale, Ilio Barba, Maddalena De Maria, Ruggero Mottolese, Marcella Maugeri-Saccà, Marcello |
author_facet | Vici, Patrizia Buglioni, Simonetta Sergi, Domenico Pizzuti, Laura Di Lauro, Luigi Antoniani, Barbara Sperati, Francesca Terrenato, Irene Carosi, Mariantonia Gamucci, Teresa Dattilo, Rosanna Bartucci, Monica Vincenzoni, Cristina Mariani, Luciano Vizza, Enrico Sanguineti, Giuseppe Gadducci, Angiolo Vitale, Ilio Barba, Maddalena De Maria, Ruggero Mottolese, Marcella Maugeri-Saccà, Marcello |
author_sort | Vici, Patrizia |
collection | PubMed |
description | Cervical cancer cells commonly harbour a defective G(1)/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G(2)/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 cervical cancer patients treated with neoadjuvant chemotherapy, we investigated whether the levels of phosphorylated Wee1 (pWee1), a key G(2)/M checkpoint kinase, and γ-H2AX, a marker of DNA double-strand breaks, discriminated between patients with a pathological complete response (pCR) and those with residual disease. We also tested the association between pWee1 and phosphorylated Chk1 (pChk1), a kinase acting upstream Wee1 in the G(2)/M checkpoint pathway. pWee1, γ-H2AX and pChk1 were retrospectively assessed in diagnostic biopsies by immunohistochemistry. The degrees of pWee1 and pChk1 expression were defined using three different classification methods, i.e., staining intensity, Allred score, and a multiplicative score. γ-H2AX was analyzed both as continuous and categorical variable. Irrespective of the classification used, elevated levels of pWee1 and γ-H2AX were significantly associated with a lower rate of pCR. In univariate and multivariate analyses, pWee1 and γ-H2AX were both associated with reduced pCR. Internal validation conducted through a re-sampling without replacement procedure confirmed the robustness of the multivariate model. Finally, we found a significant association between pWee1 and pChk1. The message conveyed by the present analysis is that biomarkers of DNA damage and repair may predict the efficacy of neoadjuvant chemotherapy in cervical cancer. Further studies are warranted to prospectively validate these encouraging findings. |
format | Online Article Text |
id | pubmed-4773222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47732222016-03-07 DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis Vici, Patrizia Buglioni, Simonetta Sergi, Domenico Pizzuti, Laura Di Lauro, Luigi Antoniani, Barbara Sperati, Francesca Terrenato, Irene Carosi, Mariantonia Gamucci, Teresa Dattilo, Rosanna Bartucci, Monica Vincenzoni, Cristina Mariani, Luciano Vizza, Enrico Sanguineti, Giuseppe Gadducci, Angiolo Vitale, Ilio Barba, Maddalena De Maria, Ruggero Mottolese, Marcella Maugeri-Saccà, Marcello PLoS One Research Article Cervical cancer cells commonly harbour a defective G(1)/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G(2)/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 cervical cancer patients treated with neoadjuvant chemotherapy, we investigated whether the levels of phosphorylated Wee1 (pWee1), a key G(2)/M checkpoint kinase, and γ-H2AX, a marker of DNA double-strand breaks, discriminated between patients with a pathological complete response (pCR) and those with residual disease. We also tested the association between pWee1 and phosphorylated Chk1 (pChk1), a kinase acting upstream Wee1 in the G(2)/M checkpoint pathway. pWee1, γ-H2AX and pChk1 were retrospectively assessed in diagnostic biopsies by immunohistochemistry. The degrees of pWee1 and pChk1 expression were defined using three different classification methods, i.e., staining intensity, Allred score, and a multiplicative score. γ-H2AX was analyzed both as continuous and categorical variable. Irrespective of the classification used, elevated levels of pWee1 and γ-H2AX were significantly associated with a lower rate of pCR. In univariate and multivariate analyses, pWee1 and γ-H2AX were both associated with reduced pCR. Internal validation conducted through a re-sampling without replacement procedure confirmed the robustness of the multivariate model. Finally, we found a significant association between pWee1 and pChk1. The message conveyed by the present analysis is that biomarkers of DNA damage and repair may predict the efficacy of neoadjuvant chemotherapy in cervical cancer. Further studies are warranted to prospectively validate these encouraging findings. Public Library of Science 2016-03-01 /pmc/articles/PMC4773222/ /pubmed/26930412 http://dx.doi.org/10.1371/journal.pone.0149872 Text en © 2016 Vici et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Vici, Patrizia Buglioni, Simonetta Sergi, Domenico Pizzuti, Laura Di Lauro, Luigi Antoniani, Barbara Sperati, Francesca Terrenato, Irene Carosi, Mariantonia Gamucci, Teresa Dattilo, Rosanna Bartucci, Monica Vincenzoni, Cristina Mariani, Luciano Vizza, Enrico Sanguineti, Giuseppe Gadducci, Angiolo Vitale, Ilio Barba, Maddalena De Maria, Ruggero Mottolese, Marcella Maugeri-Saccà, Marcello DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title | DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title_full | DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title_fullStr | DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title_full_unstemmed | DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title_short | DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis |
title_sort | dna damage and repair biomarkers in cervical cancer patients treated with neoadjuvant chemotherapy: an exploratory analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773222/ https://www.ncbi.nlm.nih.gov/pubmed/26930412 http://dx.doi.org/10.1371/journal.pone.0149872 |
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