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The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy

BACKGROUND: High expression of Stathmin 1 (STMN1) protein is related to a poor prognosis in various tumors, including breast cancer. In our previous study, a phospho-STMN1 signature was conducted to predict outcomes in adjuvantly treated breast cancer patients. This study aimed to explore the relati...

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Autores principales: Xie, Zhen, Zhen, Tiantian, Lin, Ying, Shao, Nan, Kuang, Xiaying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742056/
https://www.ncbi.nlm.nih.gov/pubmed/36518803
http://dx.doi.org/10.21037/gs-22-628
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author Xie, Zhen
Zhen, Tiantian
Lin, Ying
Shao, Nan
Kuang, Xiaying
author_facet Xie, Zhen
Zhen, Tiantian
Lin, Ying
Shao, Nan
Kuang, Xiaying
author_sort Xie, Zhen
collection PubMed
description BACKGROUND: High expression of Stathmin 1 (STMN1) protein is related to a poor prognosis in various tumors, including breast cancer. In our previous study, a phospho-STMN1 signature was conducted to predict outcomes in adjuvantly treated breast cancer patients. This study aimed to explore the relationship of STMN1 expression with our phospho-STMN1 signature and the prognosis of patients treated with neoadjuvant chemotherapy (NACT). METHODS: A retrospective analysis of 116 patients who received NACT in The First Affiliated Hospital of Sun Yat-sen University between December 2008 and March 2016 was conducted. Patients were followed up through telephone once a year until 2022. The levels of STMN1, Ser16, Ser25, Ser38, and Ser63 phosphorylation and GRP78 expression in pre-NACT biopsy specimens from the patients were detected by immunohistochemistry. The recurrence risk score for each patient was calculated using the p-STMN1/GRP78 model. Clinical and pathological parameters, pathological complete response and objective response rates, and survival data were analyzed. RESULTS: In patients with NACT-treated breast cancer, high levels of STMN1, Ser25 phosphorylation, Ser38 phosphorylation, and GRP78 were related to worse disease-free survival (DFS), as was a high p-STMN1/GRP78 model risk score. In contrast, high Ser16 and Ser63 phosphorylation levels were related to better DFS [p-STMN1/GRP78 model: P=0.002, HR =0.180 (0.061–0.534); STMN1: P=0.001, HR =0.290 (0.147–0.572); Ser16: P=0.036, HR =2.019 (1.049–3.886); Ser25: P=0.013, HR =0.392 (0.188-0.819); Ser38: P=0.001, HR =0.293 (0.153–0.559); Ser63: P=0.006, HR =3.346 (1.407–7.961); GRP78: P=0.010, HR =0.417 (0.214–0.815)]. However, no significant statistical difference was found in the multivariate regression. The relationship between these markers and the therapeutic effect of NACT (pathological complete response and objective response) showed the same tendency with survival. The area under the receiver operating characteristic curve for the p-STMN1/GRP78 model was 0.790 (P=0.001) with sensitivity of 70% and specificity of 74%. CONCLUSIONS: The expression and serine phosphorylation status of STMN1 may be beneficial as biomarkers for predicting the prognosis of breast cancer patients treated with NACT. Our p-STMN1/GRP78 model could become a widely applied signature for assessing the metastatic risk of breast cancer patients, potentially facilitating their individualized management before NACT.
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spelling pubmed-97420562022-12-13 The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy Xie, Zhen Zhen, Tiantian Lin, Ying Shao, Nan Kuang, Xiaying Gland Surg Original Article BACKGROUND: High expression of Stathmin 1 (STMN1) protein is related to a poor prognosis in various tumors, including breast cancer. In our previous study, a phospho-STMN1 signature was conducted to predict outcomes in adjuvantly treated breast cancer patients. This study aimed to explore the relationship of STMN1 expression with our phospho-STMN1 signature and the prognosis of patients treated with neoadjuvant chemotherapy (NACT). METHODS: A retrospective analysis of 116 patients who received NACT in The First Affiliated Hospital of Sun Yat-sen University between December 2008 and March 2016 was conducted. Patients were followed up through telephone once a year until 2022. The levels of STMN1, Ser16, Ser25, Ser38, and Ser63 phosphorylation and GRP78 expression in pre-NACT biopsy specimens from the patients were detected by immunohistochemistry. The recurrence risk score for each patient was calculated using the p-STMN1/GRP78 model. Clinical and pathological parameters, pathological complete response and objective response rates, and survival data were analyzed. RESULTS: In patients with NACT-treated breast cancer, high levels of STMN1, Ser25 phosphorylation, Ser38 phosphorylation, and GRP78 were related to worse disease-free survival (DFS), as was a high p-STMN1/GRP78 model risk score. In contrast, high Ser16 and Ser63 phosphorylation levels were related to better DFS [p-STMN1/GRP78 model: P=0.002, HR =0.180 (0.061–0.534); STMN1: P=0.001, HR =0.290 (0.147–0.572); Ser16: P=0.036, HR =2.019 (1.049–3.886); Ser25: P=0.013, HR =0.392 (0.188-0.819); Ser38: P=0.001, HR =0.293 (0.153–0.559); Ser63: P=0.006, HR =3.346 (1.407–7.961); GRP78: P=0.010, HR =0.417 (0.214–0.815)]. However, no significant statistical difference was found in the multivariate regression. The relationship between these markers and the therapeutic effect of NACT (pathological complete response and objective response) showed the same tendency with survival. The area under the receiver operating characteristic curve for the p-STMN1/GRP78 model was 0.790 (P=0.001) with sensitivity of 70% and specificity of 74%. CONCLUSIONS: The expression and serine phosphorylation status of STMN1 may be beneficial as biomarkers for predicting the prognosis of breast cancer patients treated with NACT. Our p-STMN1/GRP78 model could become a widely applied signature for assessing the metastatic risk of breast cancer patients, potentially facilitating their individualized management before NACT. AME Publishing Company 2022-11 /pmc/articles/PMC9742056/ /pubmed/36518803 http://dx.doi.org/10.21037/gs-22-628 Text en 2022 Gland Surgery. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Xie, Zhen
Zhen, Tiantian
Lin, Ying
Shao, Nan
Kuang, Xiaying
The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title_full The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title_fullStr The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title_full_unstemmed The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title_short The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
title_sort prognostic role of a phospho-stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742056/
https://www.ncbi.nlm.nih.gov/pubmed/36518803
http://dx.doi.org/10.21037/gs-22-628
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