TY - JOUR
T1 - Development of prediction models for the sensitivity of oral squamous cell carcinomas to preoperative S-1 administration
AU - Shiiba, Masashi
AU - Yamagami, Hitomi
AU - Sudo, Tadashi
AU - Tomokuni, Yosuke
AU - Kashiwabara, Daisuke
AU - Kirita, Tadaaki
AU - Kusukawa, Jingo
AU - Komiya, Masamichi
AU - Tei, Kanchu
AU - Kitagawa, Yoshimasa
AU - Imai, Yutaka
AU - Kawamata, Hitoshi
AU - Bukawa, Hiroki
AU - Satomura, Kazuhito
AU - Oki, Hidero
AU - Shinozuka, Keiji
AU - Sugihara, Kazumasa
AU - Sugiura, Tsuyoshi
AU - Sekine, Joji
AU - Yokoe, Hidetaka
AU - Saito, Kengo
AU - Tanzawa, Hideki
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/8
Y1 - 2020/8
N2 - S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance.
AB - S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance.
KW - 5-Fluorouracil
KW - Anti-tumor agent
KW - Clinical genetics
KW - Genetics
KW - Oncology
KW - Oral squamous cell carcinoma
KW - OSCC
KW - Pharmacology
KW - Prediction model
KW - S-1
KW - Surgery
UR - http://www.scopus.com/inward/record.url?scp=85088982028&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2020.e04601
DO - 10.1016/j.heliyon.2020.e04601
M3 - Article
AN - SCOPUS:85088982028
SN - 2405-8440
VL - 6
JO - Heliyon
JF - Heliyon
IS - 8
M1 - e04601
ER -