A serum piRNA signature as promising non-invasive diagnostic and prognostic biomarkers for colorectal cancer

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.