DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study

Autores
Sottile Fleury, Mayra Lis; Cuello Carrión, Fernando Darío; Vargas Roig, Laura Maria; Nadin, Silvina Beatriz
Año de publicación
2024
Idioma
inglés
Tipo de recurso
conjunto de datos
Estado
Descripción
Platinum analogues are commonly used for cancer treatment. There is increasing interest in finding biomarkers which could predict and overcome resistance, because to date there is no reliable predictive/prognostic marker for these compounds. Here we studied the immunohistochemical (IHC) expression of proteins involved in DNA damage response and repair (γH2AX, 53BP1, ERCC1, MLH1, and MSH2) in primary tumor tissues from patients treated with platinum-based chemotherapy. Levels and localization of HSP27 and phospho-(Thr5/7)-HSP90α (p-HSP90α) were also determined. The implications in clinical response, disease free survival (DFS) and overall survival (OS) were analysed. High γH2AX and 53BP1 expressions were associated with poor clinical response. Nuclear p-HSP90α, as well as nuclear absence and low cytoplasmic expression of HSP27 correlated with good response. Patients with high γH2AX and high cytoplasmic HSP27 expressions had shorter OS and DFS. MLH1, MSH2 or ERCC1 were not associated with clinical response or survival. We report the potential utility of p-HSP90α, HSP27, γH2AX and 53BP1 as predictive/prognostic markers for platinum-based chemotherapy. We present the first study that evaluates the predictive and prognostic value of p-HSP90α in primary tumors. Our research opens new possibilities for clinical oncology and shows the usefulness of IHC for predicting chemotherapy response and prognosis in cancer.
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Protección de datos personales (Ley 25.326)
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/225602
Acceder
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spelling DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory studySottile Fleury, Mayra LisCuello Carrión, Fernando DaríoVargas Roig, Laura MariaNadin, Silvina Beatrizhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Platinum analogues are commonly used for cancer treatment. There is increasing interest in finding biomarkers which could predict and overcome resistance, because to date there is no reliable predictive/prognostic marker for these compounds. Here we studied the immunohistochemical (IHC) expression of proteins involved in DNA damage response and repair (γH2AX, 53BP1, ERCC1, MLH1, and MSH2) in primary tumor tissues from patients treated with platinum-based chemotherapy. Levels and localization of HSP27 and phospho-(Thr5/7)-HSP90α (p-HSP90α) were also determined. The implications in clinical response, disease free survival (DFS) and overall survival (OS) were analysed. High γH2AX and 53BP1 expressions were associated with poor clinical response. Nuclear p-HSP90α, as well as nuclear absence and low cytoplasmic expression of HSP27 correlated with good response. Patients with high γH2AX and high cytoplasmic HSP27 expressions had shorter OS and DFS. MLH1, MSH2 or ERCC1 were not associated with clinical response or survival. We report the potential utility of p-HSP90α, HSP27, γH2AX and 53BP1 as predictive/prognostic markers for platinum-based chemotherapy. We present the first study that evaluates the predictive and prognostic value of p-HSP90α in primary tumors. Our research opens new possibilities for clinical oncology and shows the usefulness of IHC for predicting chemotherapy response and prognosis in cancer.Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina2024info:ar-repo/semantics/conjuntoDeDatosv1.0info:eu-repo/semantics/dataSetapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheethttp://hdl.handle.net/11336/225602Sottile Fleury, Mayra Lis; Cuello Carrión, Fernando Darío; Vargas Roig, Laura Maria; Nadin, Silvina Beatriz; (2024): DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study. Consejo Nacional de Investigaciones Científicas y Técnicas. (dataset). http://hdl.handle.net/11336/225602CONICET DigitalCONICETenginfo:eu-repo/grantAgreement/Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica/PICT 2015-1171info:eu-repo/semantics/restrictedAccessProtección de datos personales (Ley 25.326)reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:50:56Zoai:ri.conicet.gov.ar:11336/225602instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:50:56.787CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
title DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
spellingShingle DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
Sottile Fleury, Mayra Lis
title_short DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
title_full DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
title_fullStr DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
title_full_unstemmed DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
title_sort DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study
dc.creator.none.fl_str_mv Sottile Fleury, Mayra Lis
Cuello Carrión, Fernando Darío
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author Sottile Fleury, Mayra Lis
author_facet Sottile Fleury, Mayra Lis
Cuello Carrión, Fernando Darío
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author_role author
author2 Cuello Carrión, Fernando Darío
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author2_role author
author
author
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Platinum analogues are commonly used for cancer treatment. There is increasing interest in finding biomarkers which could predict and overcome resistance, because to date there is no reliable predictive/prognostic marker for these compounds. Here we studied the immunohistochemical (IHC) expression of proteins involved in DNA damage response and repair (γH2AX, 53BP1, ERCC1, MLH1, and MSH2) in primary tumor tissues from patients treated with platinum-based chemotherapy. Levels and localization of HSP27 and phospho-(Thr5/7)-HSP90α (p-HSP90α) were also determined. The implications in clinical response, disease free survival (DFS) and overall survival (OS) were analysed. High γH2AX and 53BP1 expressions were associated with poor clinical response. Nuclear p-HSP90α, as well as nuclear absence and low cytoplasmic expression of HSP27 correlated with good response. Patients with high γH2AX and high cytoplasmic HSP27 expressions had shorter OS and DFS. MLH1, MSH2 or ERCC1 were not associated with clinical response or survival. We report the potential utility of p-HSP90α, HSP27, γH2AX and 53BP1 as predictive/prognostic markers for platinum-based chemotherapy. We present the first study that evaluates the predictive and prognostic value of p-HSP90α in primary tumors. Our research opens new possibilities for clinical oncology and shows the usefulness of IHC for predicting chemotherapy response and prognosis in cancer.
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Platinum analogues are commonly used for cancer treatment. There is increasing interest in finding biomarkers which could predict and overcome resistance, because to date there is no reliable predictive/prognostic marker for these compounds. Here we studied the immunohistochemical (IHC) expression of proteins involved in DNA damage response and repair (γH2AX, 53BP1, ERCC1, MLH1, and MSH2) in primary tumor tissues from patients treated with platinum-based chemotherapy. Levels and localization of HSP27 and phospho-(Thr5/7)-HSP90α (p-HSP90α) were also determined. The implications in clinical response, disease free survival (DFS) and overall survival (OS) were analysed. High γH2AX and 53BP1 expressions were associated with poor clinical response. Nuclear p-HSP90α, as well as nuclear absence and low cytoplasmic expression of HSP27 correlated with good response. Patients with high γH2AX and high cytoplasmic HSP27 expressions had shorter OS and DFS. MLH1, MSH2 or ERCC1 were not associated with clinical response or survival. We report the potential utility of p-HSP90α, HSP27, γH2AX and 53BP1 as predictive/prognostic markers for platinum-based chemotherapy. We present the first study that evaluates the predictive and prognostic value of p-HSP90α in primary tumors. Our research opens new possibilities for clinical oncology and shows the usefulness of IHC for predicting chemotherapy response and prognosis in cancer.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:ar-repo/semantics/conjuntoDeDatos
v1.0
info:eu-repo/semantics/dataSet
format dataSet
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/225602
Sottile Fleury, Mayra Lis; Cuello Carrión, Fernando Darío; Vargas Roig, Laura Maria; Nadin, Silvina Beatriz; (2024): DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study. Consejo Nacional de Investigaciones Científicas y Técnicas. (dataset). http://hdl.handle.net/11336/225602
CONICET Digital
CONICET
url http://hdl.handle.net/11336/225602
identifier_str_mv Sottile Fleury, Mayra Lis; Cuello Carrión, Fernando Darío; Vargas Roig, Laura Maria; Nadin, Silvina Beatriz; (2024): DNA damage repair proteins, HSP27 and phosphorylated-HSP90alpha as predictive/prognostic biomarkers of platinum-based cancer chemotherapy: An exploratory study. Consejo Nacional de Investigaciones Científicas y Técnicas. (dataset). http://hdl.handle.net/11336/225602
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica/PICT 2015-1171
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
Protección de datos personales (Ley 25.326)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv Protección de datos personales (Ley 25.326)
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