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Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is...

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Autores principales: Nanno, Shigenori, Fukuda, Takeshi, Noda, Takuya, Uchikura, Eijiro, Awazu, Yuichiro, Imai, Kenji, Yamauchi, Makoto, Yasui, Tomoyo, Sumi, Toshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468808/
https://www.ncbi.nlm.nih.gov/pubmed/36157319
http://dx.doi.org/10.3892/mco.2022.2580
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author Nanno, Shigenori
Fukuda, Takeshi
Noda, Takuya
Uchikura, Eijiro
Awazu, Yuichiro
Imai, Kenji
Yamauchi, Makoto
Yasui, Tomoyo
Sumi, Toshiyuki
author_facet Nanno, Shigenori
Fukuda, Takeshi
Noda, Takuya
Uchikura, Eijiro
Awazu, Yuichiro
Imai, Kenji
Yamauchi, Makoto
Yasui, Tomoyo
Sumi, Toshiyuki
author_sort Nanno, Shigenori
collection PubMed
description Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer.
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spelling pubmed-94688082022-09-24 Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy Nanno, Shigenori Fukuda, Takeshi Noda, Takuya Uchikura, Eijiro Awazu, Yuichiro Imai, Kenji Yamauchi, Makoto Yasui, Tomoyo Sumi, Toshiyuki Mol Clin Oncol Articles Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer. D.A. Spandidos 2022-08-11 /pmc/articles/PMC9468808/ /pubmed/36157319 http://dx.doi.org/10.3892/mco.2022.2580 Text en Copyright: © Nanno et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Nanno, Shigenori
Fukuda, Takeshi
Noda, Takuya
Uchikura, Eijiro
Awazu, Yuichiro
Imai, Kenji
Yamauchi, Makoto
Yasui, Tomoyo
Sumi, Toshiyuki
Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title_full Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title_fullStr Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title_full_unstemmed Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title_short Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
title_sort fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468808/
https://www.ncbi.nlm.nih.gov/pubmed/36157319
http://dx.doi.org/10.3892/mco.2022.2580
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