Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context

Background: Approximately 60% of patients with colorectal cancer (CRC) undergo either local recurrence or distant metastases after surgery. Current prognostic biomarkers are insufficient to predict recurrence of CRC and provide little forecast information about what patients are likely to receive be...

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Main Authors: Dengbo Ji, Meng Qiao, Yunfeng Yao, Ming Li, Hailong Chen, Qi Dong, Jinying Jia, Xinxin Cui, Zhaowei Li, Jinhong Xia, Jin Gu
Format: Article
Language:English
Published: Elsevier 2018-09-01
Series:EBioMedicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396418303268
id doaj-95ec3f07b93446208a12a6df9b1fd109
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Dengbo Ji
Meng Qiao
Yunfeng Yao
Ming Li
Hailong Chen
Qi Dong
Jinying Jia
Xinxin Cui
Zhaowei Li
Jinhong Xia
Jin Gu
spellingShingle Dengbo Ji
Meng Qiao
Yunfeng Yao
Ming Li
Hailong Chen
Qi Dong
Jinying Jia
Xinxin Cui
Zhaowei Li
Jinhong Xia
Jin Gu
Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
EBioMedicine
author_facet Dengbo Ji
Meng Qiao
Yunfeng Yao
Ming Li
Hailong Chen
Qi Dong
Jinying Jia
Xinxin Cui
Zhaowei Li
Jinhong Xia
Jin Gu
author_sort Dengbo Ji
title Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
title_short Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
title_full Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
title_fullStr Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
title_full_unstemmed Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
title_sort serum-based microrna signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsresearch in context
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2018-09-01
description Background: Approximately 60% of patients with colorectal cancer (CRC) undergo either local recurrence or distant metastases after surgery. Current prognostic biomarkers are insufficient to predict recurrence of CRC and provide little forecast information about what patients are likely to receive benefit from the adjuvant chemotherapy. As microRNAs (miRNAs) constantly exist in human serum and being used to predict the prognosis of a various cancers, this study was designed to identify miRNA-based circulating biomarkers to predict clinical outcomes of CRC. Methods: A serum-focused miRNA expression was used to investigate if miRNA expression profiles could predict the clinical outcomes of patients with CRC. We created miRNA signature profiles associated in the training set (n = 40), and further validated its prediction in two independent testing cohorts. Results: Using Cox regression and risk-score analysis, we identified a four-miRNA signature (miR-652-3p, miR-342-3p, miR-501-3p and miR-328-3p) for the prediction of tumor relapse and the overall survival(OS) of patients with CRC in the training set (n = 40). This miRNA signature was further validated in a testing set (n = 226) and another independent cohort (n = 56). A high-risk signature score was significantly associated with CRC tumor recurrence and poor treatment outcome. Multivariable Cox regression models indicated that the risk score, based on the four-miRNA signature, was an independent prognostic classifier for patients with CRC. Conclusions: The serum miRNA signature may serve as a minimally invasive predictor for tumor relapse and treatment outcome in patients with CRC and provide a useful reference for treatment selection. Keywords: Serum-based microRNA signature, Colorectal cancer, Adjuvant chemotherapy, Prognostic biomarker
url http://www.sciencedirect.com/science/article/pii/S2352396418303268
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spelling doaj-95ec3f07b93446208a12a6df9b1fd1092020-11-25T01:54:57ZengElsevierEBioMedicine2352-39642018-09-0135189197Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in contextDengbo Ji0Meng Qiao1Yunfeng Yao2Ming Li3Hailong Chen4Qi Dong5Jinying Jia6Xinxin Cui7Zhaowei Li8Jinhong Xia9Jin Gu10Key laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, ChinaKey laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, China; Peking-Tsinghua Center for Life Sciences, China; Peking University S.G. Hospital, China; Corresponding author at: Key laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Haidian District, Beijing 100142, China.Background: Approximately 60% of patients with colorectal cancer (CRC) undergo either local recurrence or distant metastases after surgery. Current prognostic biomarkers are insufficient to predict recurrence of CRC and provide little forecast information about what patients are likely to receive benefit from the adjuvant chemotherapy. As microRNAs (miRNAs) constantly exist in human serum and being used to predict the prognosis of a various cancers, this study was designed to identify miRNA-based circulating biomarkers to predict clinical outcomes of CRC. Methods: A serum-focused miRNA expression was used to investigate if miRNA expression profiles could predict the clinical outcomes of patients with CRC. We created miRNA signature profiles associated in the training set (n = 40), and further validated its prediction in two independent testing cohorts. Results: Using Cox regression and risk-score analysis, we identified a four-miRNA signature (miR-652-3p, miR-342-3p, miR-501-3p and miR-328-3p) for the prediction of tumor relapse and the overall survival(OS) of patients with CRC in the training set (n = 40). This miRNA signature was further validated in a testing set (n = 226) and another independent cohort (n = 56). A high-risk signature score was significantly associated with CRC tumor recurrence and poor treatment outcome. Multivariable Cox regression models indicated that the risk score, based on the four-miRNA signature, was an independent prognostic classifier for patients with CRC. Conclusions: The serum miRNA signature may serve as a minimally invasive predictor for tumor relapse and treatment outcome in patients with CRC and provide a useful reference for treatment selection. Keywords: Serum-based microRNA signature, Colorectal cancer, Adjuvant chemotherapy, Prognostic biomarkerhttp://www.sciencedirect.com/science/article/pii/S2352396418303268