An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis.
Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Shinichiro
S
Empuku
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Kentaro
K
Nakajima
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Tomonori
T
Akagi
Department of Computer Science, Fukuyama University Faculty of Engineering, Fukuyama, Hiroshima 720-0292, Japan.
Kunihiko
K
Kaneko
Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Naoki
N
Hijiya
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Tsuyoshi
T
Etoh
Center for Community Medicine, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Norio
N
Shiraishi
Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Masatsugu
M
Moriyama
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
Masafumi
M
Inomata
histological response; microarray analysis; preoperative chemoradiotherapy; principle component analysis; rectal cancer