Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer.
OBJECTIVE
Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment.


METHODS
Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo.


RESULTS
In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained.


CONCLUSIONS
A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.
Department of Radiology, Sapporo Medical University School of Medicine, Japan. Electronic address: someya@sapmed.ac.jp.
Masanori
M
Someya
Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Hiroyuki
H
Yamamoto
The Institute of Medical Science Hospital, The University of Tokyo, Japan.
Masanori
M
Nojima
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Masakazu
M
Hori
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Kunihiko
K
Tateoka
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Kensei
K
Nakata
Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno-shi, Japan.
Masaru
M
Takagi
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Masato
M
Saito
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Naoki
N
Hirokawa
Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Japan.
Takashi
T
Tokino
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Koh-Ichi
K
Sakata
D000368:Aged; D034961:Antigens, Nuclear / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D012007:Rectum / Q000293:injuries*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen
Late rectal toxicity; Micro RNA; Prostate cancer; RNA array; Radiotherapy