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T-box 2 expression is a useful indicator of the response to neoadjuvant chemotherapy for patients with locally advanced uterine cervical squamous cell carcinoma
Authors:Yuta Inoue  Takeshi Fukuda  Shigenori Nanno  Yuichiro Awazu  Masahiro Shimomura  Hiroaki Matsubara  Makoto Yamauchi  Tomoyo Yasui  Toshiyuki Sumi
Affiliation:Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Abstract:Platinum-based concurrent chemoradiotherapy is the standard treatment for patients with locally advanced uterine cervical squamous cell carcinoma. Reducing the tumor size by administering neoadjuvant chemotherapy (NAC) is beneficial for successful hysterectomy, resulting in a more favorable prognosis. Therefore, identifying biomarkers that predict the effectiveness of NAC in patients with cervical squamous cell carcinoma remains a priority. Cancer cells widely express T-box 2 (TBX2), which contributes to the resistance to DNA-damaging chemotherapeutic agents. The present study aimed to determine the association between TBX2 protein expression in tumor tissues and the efficacy of NAC in locally advanced uterine cervical squamous cell carcinoma using immunohistochemistry. Data from 46 patients with locally advanced uterine cervical squamous cell carcinoma were classified into two groups based on their effective or ineffective response to NAC treatment. In addition, the effect of small interfering RNA-mediated knockdown of TBX2 on the sensitivity of cervical cancer cells to cisplatin was investigated in vitro. The results revealed that there were no significant differences in patient clinicopathological features between the NAC effective and NAC ineffective groups. The overall survival of the NAC effective group was significantly improved compared with the NAC ineffective group (P=0.007). Tumors from the NAC effective group also had significantly downregulated TBX2 expression levels compared with those from the NAC ineffective group (P=0.0138). Of note, decreased TBX2 expression was indicated to be significantly associated with higher sensitivity to NAC (P=0.009). The low TBX2 expression group had a more favorable overall survival compared with the high TBX2 expression group (P=0.049). Furthermore, knockdown of TBX2 expression significantly increased cancer cell sensitivity to cisplatin in vitro. In conclusion, the results of the present study suggested that TBX2 expression may be a useful predictor of the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma.
Keywords:uterine cervical squamous cell carcinoma   T-box 2   neoadjuvant chemotherapy   chemoresistance   predictive biomarker
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