A serum piRNA signature as promising non-invasive diagnostic and prognostic biomarkers for colorectal cancer
Received 4 November 2018
Accepted for publication 6 March 2019
Published 29 April 2019 Volume 2019:11 Pages 3703—3720
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Dr Chien-Feng Li
Ailin Qu,1 Wenfei Wang,2,3 Yongmei Yang,4 Xin Zhang,4 Yuhuan Dong,4 Guixi Zheng,4 Qiuyan Wu,4 Mingjin Zou,4 Lutao Du,1 Yunshan Wang,1 Chuanxin Wang1
1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, People’s Republic of China; 2Humanistic Medicine Research Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 3Humanistic Medicine Research Center, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 4Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong 250012, People’s Republic of China
Purpose: Piwi-interacting RNAs (piRNAs) are a novel class of small non-coding RNAs, which are not easily degraded but detectable in human body fluids. Recent studies have shown that aberrant piRNA expression is a signature feature across multiple tumor types. However, the expressions of piRNAs in serum of tumor patients and their potential clinical values remain largely unclear.
Patients and methods: High-throughput sequencing was performed to investigate the serum piRNA profiles, followed by evaluations in serum samples of 220 colorectal cancer (CRC) patients and 220 healthy controls using reverse transcription quantitative real-time PCR (RT-qPCR). Biomarker panels including piRNA-based Panel I and carcinoembryonic antigen (CEA)-based Panel II, were developed by logistic regression model, and their diagnostic potentials were compared. Fagan’s nomogram was plotted to promote clinical application.
Results: We identified five differentially expressed serum piRNAs (piR-001311, piR-004153, piR-017723, piR-017724 and piR-020365), which, when combined in the piRNA-based Panel I, outperformed the CEA-based Panel II (P<0.001) and could detect CRC with an area under the receiver operating characteristic curve of 0.867. In addition, Kaplan–Meier analysis showed that patients with low serum piR-017724 level had worse overall survival (OS) and progression-free survival (PFS). In multivariate Cox regression analysis, serum piR-017724 was an independent prognostic factor for OS and PFS (P<0.05).
Conclusion: Our findings suggest serum piRNA expression signatures have potential for use as biomarkers for CRC detection and to predict prognosis at the time of diagnosis.
Keywords: serum piRNA, colorectal cancer, diagnosis, prognosis, nomogram
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