Sirtuin1 expression predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Teramae,Masatomo; Fukuda,Takeshi; Wada,Takuma; Kawanishi,Masaru; Imai,Kenji; Yamauchi,Makoto; Yasui,Tomoyo; Sumi,Toshiyuki

doi:10.3892/mco.2014.427

Sirtuin1 expression predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Authors:
- Masatomo Teramae
- Takeshi Fukuda
- Takuma Wada
- Masaru Kawanishi
- 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, Abeno‑ku, Osaka 545‑8585, Japan
Published online on: September 24, 2014 https://doi.org/10.3892/mco.2014.427
Pages: 73-78

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Abstract

Cisplatin‑based, cyclic balloon‑occluded arterial infusion, neoadjuvant chemotherapy (NAC) has previously been reported to enable hysterectomy in patients with locally advanced cervical cancer. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)‑dependent histone deacetylase that deacetylates a number of proteins and is overexpressed in several human malignancies. Upregulation of SIRT1 has been reported to induce tumorigenesis and chemoresistance. To assess the role of SIRT1 in uterine cervical cancer, the outcomes in 62 patients aged <70 years with locally advanced International Federation of Gynecology and Obstetrics (FIGO) stage IIIA‑IIIB uterine cervical cancer were reviewed between 1995 and 2010. Tumor samples were obtained by biopsy prior to NAC. The patients were separated into two groups. One group comprised of the patients in which NAC was effective, surgery and radiotherapy were performed (NAC+OP+R group; n=35), and the second group contained patients in which NAC was ineffective and radiation therapy was performed (NAC+R group; n=27). SIRT1 and p53 expression was assessed immunohistochemically in paraffin‑embedded sections. SIRT1 expression was significantly higher in the NAC+R compared to the NAC+OP+R group (P<0.001), as was p53 expression (P=0.001). The overall survival time was significantly longer in the NAC+OP+R compared to the NAC+R group (P=0.001). Following the division of patients into two groups based on SIRT1 level, low (weighted score ≤4, n=30), and high level (weighted score ≥6, n=32) groups, the former group was significantly more sensitive to NAC (P<0.001). Collectively, these results indicate that SIRT1 expression may predict the efficacy of NAC as a treatment for locally advanced, uterine cervical cancer.

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