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

doi:10.3892/mco.2022.2580

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

Authors:
- Shigenori Nanno
- Takeshi Fukuda
- Takuya Noda
- Eijiro Uchikura
- Yuichiro Awazu
- Kenji Imai
- Makoto Yamauchi
- Tomoyo Yasui
- Toshiyuki Sumi
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Affiliations: Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka 545‑8585, Japan, Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545‑8585, Japan
Published online on: August 11, 2022 https://doi.org/10.3892/mco.2022.2580
Article Number: 147
Copyright: © Nanno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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