Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patientsResearch in context
Dengbo Ji,
Meng Qiao,
Yunfeng Yao,
Ming Li,
Hailong Chen,
Qi Dong,
Jinying Jia,
Xinxin Cui,
Zhaowei Li,
Jinhong Xia,
Jin Gu
Affiliations
Dengbo Ji
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
Meng Qiao
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
Yunfeng Yao
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
Ming Li
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
Hailong Chen
Cancer 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, China
Qi Dong
Cancer 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, China
Jinying Jia
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
Xinxin Cui
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
Zhaowei Li
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
Jinhong Xia
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
Jin Gu
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; 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 biomarker