DNA Damage Repair Proteins, HSP27, and Phosphorylated-HSP90α as Predictive/Prognostic Biomarkers of Platinum-based Cancer Chemotherapy: An Exploratory Study.
Antineoplastic Agents
/ therapeutic use
Biomarkers
Biomarkers, Tumor
/ metabolism
DNA Damage
DNA-Binding Proteins
/ genetics
Endonucleases
/ metabolism
HSP27 Heat-Shock Proteins
/ genetics
Heat-Shock Proteins
/ genetics
Humans
MutS Homolog 2 Protein
/ genetics
Neoplasms
/ diagnosis
Platinum Compounds
/ therapeutic use
Prognosis
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
10
08
2021
accepted:
25
04
2022
pubmed:
1
6
2022
medline:
12
7
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
Platinum analogs 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 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 Heat Shock Protein (HSP)27 and phospho-(Thr5/7)-HSP90α (p-HSP90α) were also determined. The implications in clinical response, disease-free survival and overall survival were analyzed. 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 overall survival and disease-free survival. 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 immunohistochemistry for predicting chemotherapy response and prognosis in cancer.
Identifiants
pubmed: 35639358
doi: 10.1097/PAI.0000000000001037
pii: 00129039-202207000-00004
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers
0
Biomarkers, Tumor
0
DNA-Binding Proteins
0
HSP27 Heat-Shock Proteins
0
Heat-Shock Proteins
0
Platinum Compounds
0
Endonucleases
EC 3.1.-
MutS Homolog 2 Protein
EC 3.6.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
425-434Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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