Dong Won Baek1, Gyeonghwa Kim2, Byung Woog Kang1, Hye Jin Kim3, Su Yeon Park3, Jun Seok Park3, Gyu-Seog Choi3, Min Kyu Kang4, Keun Hur5, Jong Gwang Kim6. 1. Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea. 2. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. 3. Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu, Republic of Korea. 4. Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu, Republic of Korea. 5. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. keunhur@knu.ac.kr. 6. Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea. jkk21c@knu.ac.kr.
Abstract
PURPOSE: We aimed to identify biomarkers of response to preoperative CRT in patients with LARC using comprehensive miRNA analysis. METHODS: This study included 65 rectal cancer specimens and 89 serum samples from patients diagnosed with LARC and treated with preoperative. All specimens were collected before CRT for evaluation of biologic differences between the good and poor CRT response groups (ypStage 0/I versus II/III/IV). For specific miRNA discovery, 800 miRNAs in 20 rectal cancer specimens were analyzed with a NanoString assay. For validation, a total of 65 tissue and 89 serum samples were tested with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the discovery set, 16 target miRNAs were detected. In the validation set, higher expression of three miRNAs (miR-199a/b-3p, miR-199a-5p, and miR-199b-5p) was significantly associated with better response to CRT. In the univariate survival analysis, upregulation of these three miRNAs was associated with superior relapse-free survival (RFS) and overall survival (OS). Meanwhile, only a higher level of tissue miR-199a-5p was associated with superior RFS [hazard ratio (HR), 0.0.91; 95% confidence interval (CI) 0.035-0.580; p = 0.002] and OS (HR, 0.272; 95% CI 0.023-0.658; p < 0.001) in the multivariate survival analysis. Also, a higher level of exosomal miR-199b-5p correlated with better response to CRT (p = 0.0397). CONCLUSION: High expression of tissue miR-199a/b-3p, miR-199a-5p, and miR-199b-5p was significantly associated with response to CRT, and a high level of tissue miR-199a-5p was associated with superior survival outcomes. Also, upregulated exosomal miR-199b-5p correlated with CRT response, reflecting its promise as a circulating biomarker of CRT response in patients with LARC.
PURPOSE: We aimed to identify biomarkers of response to preoperative CRT in patients with LARC using comprehensive miRNA analysis. METHODS: This study included 65 rectal cancer specimens and 89 serum samples from patients diagnosed with LARC and treated with preoperative. All specimens were collected before CRT for evaluation of biologic differences between the good and poor CRT response groups (ypStage 0/I versus II/III/IV). For specific miRNA discovery, 800 miRNAs in 20 rectal cancer specimens were analyzed with a NanoString assay. For validation, a total of 65 tissue and 89 serum samples were tested with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the discovery set, 16 target miRNAs were detected. In the validation set, higher expression of three miRNAs (miR-199a/b-3p, miR-199a-5p, and miR-199b-5p) was significantly associated with better response to CRT. In the univariate survival analysis, upregulation of these three miRNAs was associated with superior relapse-free survival (RFS) and overall survival (OS). Meanwhile, only a higher level of tissue miR-199a-5p was associated with superior RFS [hazard ratio (HR), 0.0.91; 95% confidence interval (CI) 0.035-0.580; p = 0.002] and OS (HR, 0.272; 95% CI 0.023-0.658; p < 0.001) in the multivariate survival analysis. Also, a higher level of exosomal miR-199b-5p correlated with better response to CRT (p = 0.0397). CONCLUSION: High expression of tissue miR-199a/b-3p, miR-199a-5p, and miR-199b-5p was significantly associated with response to CRT, and a high level of tissue miR-199a-5p was associated with superior survival outcomes. Also, upregulated exosomal miR-199b-5p correlated with CRT response, reflecting its promise as a circulating biomarker of CRT response in patients with LARC.
Entities:
Keywords:
Biomarker; Chemoradiotherapy; Exosome; MicroRNA; Rectal cancer
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