Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer

Abstract Background and purpose Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Materials and methods Four patients each with grade 0–1 or grade 2–3 rectal bleeding were randomly selected fo...

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Published in:Radiotherapy and oncology 2015-05, Vol.115 (2), p.235-239
Main Authors: Someya, Masanori, Yamamoto, Hiroyuki, Nojima, Masanori, Hori, Masakazu, Tateoka, Kunihiko, Nakata, Kensei, Takagi, Masaru, Saito, Masato, Hirokawa, Naoki, Tokino, Takashi, Sakata, Koh-ichi
Format: Article
Language:English
Subjects:
Aged
Antigens, Nuclear - genetics
DNA-Binding Proteins - genetics
Gastrointestinal Hemorrhage - etiology
Gastrointestinal Hemorrhage - genetics
Gene Expression Regulation
Hematology, Oncology and Palliative Medicine
Humans
Ku Autoantigen
Late rectal toxicity
Male
Micro RNA
MicroRNAs - genetics
Prostate cancer
Prostatic Neoplasms - radiotherapy
Radiation Injuries - genetics
Radiotherapy
Radiotherapy - adverse effects
Rectum - injuries
RNA array
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Summary:Abstract Background and purpose Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Materials and 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 4 Gy of X-ray ex-vivo. Results In the discovery cohort, grade 2–3 rectal bleeding was significantly higher in the Ku80 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. Conclusion A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.
ISSN:0167-8140
1879-0887
DOI:10.1016/j.radonc.2015.04.008