Circulating exosomal small RNAs are promising non-invasive diagnostic biomarkers for gastric cancer

Abstract

Dysregulation of small non-coding RNA (ncRNA) is associated with various human diseases including cancer. This study aimed to evaluate the circulating exosomal small RNAs including microRNAs (miRNAs) and P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) as sensitive and specific non-invasive biomarkers for gastric cancer (GC) diagnosis. Serum exosomal small RNA transcriptome was examined using unique molecular identifiers (UMI) small RNA sequencing. Dysregulated miRNAs and piRNAs were verified in 70 GC patients and 60 healthy controls (HC) by reverse transcription quantitative PCR. The expressions of miR-1307-3p, piR-019308, piR-004918 and piR-018569 in serum exosomes were significantly increased in GC group as compared to those in HC group. Moreover, GC patients with metastasis had significantly higher expression levels of piR-004918 and piR-019308 than GC patients without metastasis. The area under the curve (AUC) for miR-1307-3p, piR-019308, piR-004918 and piR-018569 in the GC group was 0.845, 0.820, 0.754 and 0.732, respectively. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 199 can improve the AUC of miR-1307-3p to 0.902 and piR-019308 to 0.914 for GC diagnosis. In conclusion, our findings indicate that serum exosomal piRNAs are promising non-invasive diagnostic biomarkers for GC patients and potential markers for monitoring metastasis.

Keywords: PIWI-interacting RNAs; diagnosis; gastric cancer; non-coding RNA; serum exosomes.