title: Circadian gene expression predicts patient response to neoadjuvant chemoradiation therapy for rectal cancer.
abstract: Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013. Gene expression analysis (RT-PCR) was performed in tissue samples from 20 patients showing pathological complete regression (pCR) and 20 showing non-pCR. The genes analyzed included six core clock genes (Clock, Per1, Per2, Cry1, Cry2 and Bmal1) and three downstream target genes (Wee1, Chk2 and c-Myc). Patient responses were analyzed through contrast-enhanced pelvic MRI and endorectal ultrasound, and verified by histological assessment. pCR was defined histologically as an absence of tumor cells. Among the 250 included patients, 70.8% showed regression of tumor size, and 18% showed pCR. Clock, Cry2 and Per2 expressions were significantly higher in the pCR group than in the non-pCR group (P<0.05), whereas Per1, Cry1 and Bmal1 expressions did not differ significantly between groups. Among the downstream genes involved in cell cycle regulation, c-Myc showed significantly higher expression in the pCR group (P<0.05), whereas Wee1 and Chk2 expression did not differ significantly between groups. Circadian genes are potential biomarkers for predicting whether a patient with rectal cancer would benefit from neoadjuvant chemoradiation therapy.
authors.affiliation: Department of Radiation Oncology, The Affiliated Union Hospital of Fujian Medical University Fuzhou 350001, Fujian, China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Life Sciences, Fuzhou University Fuzhou 350108, Fujian, China.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Institute of Life Sciences, Fuzhou University Fuzhou 350108, Fujian, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Bioinformatics Institute, Agency for Science, Technology and Research Singapore.
authors.forename: Hao
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Houston Medical School Houston, Texas 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, The Affiliated Union Hospital of Fujian Medical University Fuzhou 350001, Fujian, China.
authors.forename: Benhua
authors.initials: B
authors.lastname: Xu
authors.affiliation: Institute of Life Sciences, Fuzhou University Fuzhou 350108, Fujian, China.
authors.forename: Zhicao
authors.initials: Z
authors.lastname: Yue
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D002940:Circadian Rhythm / Q000235:genetics; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins
keywords: Neoadjuvant chemoradiation therapy; biomarker; circadian clock; rectal cancer