Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA

• Published in: Japanese journal of clinical oncology 2018-02, Vol.48 (2), p.167-174
• Main Authors: Someya, Masanori, Hori, Masakazu, Gocho, Toshio, Nakata, Kensei, Tsuchiya, Takaaki, Kitagawa, Mio, Hasegawa, Tomokazu, Fukushima, Yuuki, Sakata, Koh-ichi
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Aged, 80 and over; Gastrointestinal Tract - pathology; Humans; Logistic Models; Lymphocytes - metabolism; Lymphocytes - pathology; Male; MicroRNAs - metabolism; Middle Aged; Prostatic Neoplasms - complications; Prostatic Neoplasms - pathology; Radiation Injuries - etiology; Radiation Injuries - genetics; Radiotherapy Dosage; Reproducibility of Results; ROC Curve; Urogenital System - pathology
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyx181

Combining radiation dose parameters with microRNA expression by peripheral blood lymphocytes may be useful for predicting acute radiation-induced toxicity, thus contributing to personalized radiotherapy for prostate cancer. Abstract Background To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). Methods The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. Results In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1–2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. Conclusion Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.