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MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy

SIMPLE SUMMARY: The Melanoma Antigen Gene (MAGE) protein family is a large group of proteins that share a common MAGE homology domain. Many MAGE proteins are aberrantly expressed in a wide variety of cancer types and are of interest as a biomarkers in cancer and targets of immunotherapies because of...

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Autores principales: Lisica Šikić, Nataša, Petrić Miše, Branka, Tomić, Snježana, Spagnol, Giulia, Matak, Luka, Juretić, Antonio, Spagnoli, Giulio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571787/
https://www.ncbi.nlm.nih.gov/pubmed/37835391
http://dx.doi.org/10.3390/cancers15194697
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author Lisica Šikić, Nataša
Petrić Miše, Branka
Tomić, Snježana
Spagnol, Giulia
Matak, Luka
Juretić, Antonio
Spagnoli, Giulio
author_facet Lisica Šikić, Nataša
Petrić Miše, Branka
Tomić, Snježana
Spagnol, Giulia
Matak, Luka
Juretić, Antonio
Spagnoli, Giulio
author_sort Lisica Šikić, Nataša
collection PubMed
description SIMPLE SUMMARY: The Melanoma Antigen Gene (MAGE) protein family is a large group of proteins that share a common MAGE homology domain. Many MAGE proteins are aberrantly expressed in a wide variety of cancer types and are of interest as a biomarkers in cancer and targets of immunotherapies because of a subset of the proteins that are classified as cancer/testis antigens (CTAs). In ovarian cancers, MAGE-A1, -A9, and -A10 expression are associated with worse prognosis and unresponsiveness to platinum-based chemotherapy. ABSTRACT: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.
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spelling pubmed-105717872023-10-14 MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy Lisica Šikić, Nataša Petrić Miše, Branka Tomić, Snježana Spagnol, Giulia Matak, Luka Juretić, Antonio Spagnoli, Giulio Cancers (Basel) Article SIMPLE SUMMARY: The Melanoma Antigen Gene (MAGE) protein family is a large group of proteins that share a common MAGE homology domain. Many MAGE proteins are aberrantly expressed in a wide variety of cancer types and are of interest as a biomarkers in cancer and targets of immunotherapies because of a subset of the proteins that are classified as cancer/testis antigens (CTAs). In ovarian cancers, MAGE-A1, -A9, and -A10 expression are associated with worse prognosis and unresponsiveness to platinum-based chemotherapy. ABSTRACT: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers. MDPI 2023-09-23 /pmc/articles/PMC10571787/ /pubmed/37835391 http://dx.doi.org/10.3390/cancers15194697 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lisica Šikić, Nataša
Petrić Miše, Branka
Tomić, Snježana
Spagnol, Giulia
Matak, Luka
Juretić, Antonio
Spagnoli, Giulio
MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title_full MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title_fullStr MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title_full_unstemmed MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title_short MAGE-A10 Protein Expression in Advanced High Grade Serous Ovarian Cancer Is Associated with Resistance to First-Line Platinum-Based Chemotherapy
title_sort mage-a10 protein expression in advanced high grade serous ovarian cancer is associated with resistance to first-line platinum-based chemotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571787/
https://www.ncbi.nlm.nih.gov/pubmed/37835391
http://dx.doi.org/10.3390/cancers15194697
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